The Experts below are selected from a list of 285 Experts worldwide ranked by ideXlab platform
Yuji Kamijo - One of the best experts on this subject based on the ideXlab platform.
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Effects of hypertension and antihypertensive treatments on Sulfatide levels in serum and its metabolism
Hypertension Research, 2019Co-Authors: Xiao Hu, Yosuke Yamada, Makoto Harada, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids present in lipoproteins that work as modulators of thrombosis and hemostasis. Decreased serum Sulfatide levels are suggested by our previous work to be related to cardiovascular disease (CVD). Hypertension, known to be an important risk factor for CVD, may affect serum Sulfatide levels. However, how hypertension affects serum Sulfatides directly and mechanistically is unknown. To elucidate these possible mechanisms, we investigated changes in serum Sulfatide levels and their metabolism using an established experimental model of hypertension that uses continuous infusion of angiotensin II (AngII) into mice. Furthermore, we also examined the effects of four different antihypertensive drugs (losartan, irbesartan, nifedipine, and hydralazine) on serum Sulfatide metabolism. Serum levels of Sulfatides were found to be decreased in groups in which only hypertension was induced (AngII only), whereas they were increased in groups with reduced blood pressure (antihypertensives only) and ameliorated to increasingly normal levels in groups with induced hypertension that were also treated (AngII+antihypertensives). Changes in serum Sulfatides were strongly related to hepatic expression levels of cerebroside sulfotransferase (CST), which is a key enzyme involved in Sulfatide synthesis. Furthermore, the current study suggests that the primary factors affecting CST expression are oxidative stress, peroxisome proliferator-activated receptor α activity and blood pressure itself. This study demonstrates that hypertension significantly decreases levels of serum Sulfatides by reducing hepatic CST expression via various effects mediated by AngII. Antihypertensive treatments can ameliorate abnormalities in serum Sulfatide levels and may partially prevent hypertension related CVD by positively affecting Sulfatide metabolism.
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Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice
Glycoconjugate Journal, 2019Co-Authors: Yosuke Yamada, Makoto Harada, Koji Hashimoto, Ran Guo, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids that are present in lipoproteins and exert anticoagulant effects. A previous study reported decreased levels of serum Sulfatides in hemodialysis patients and suggested an association with cardiovascular disease. However, the mechanism of changes in serum Sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a chronic kidney disease (CKD) state could decrease serum Sulfatide levels using 5/6 nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished Sulfatides. 5/6NCKD mice and sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum Sulfatide levels. Hepatic Sulfatide content, which is the origin of serum Sulfatides, and the expression of Sulfatide metabolic enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum creatinine and indoxyl sulfate. The serum levels and hepatic amounts of Sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative enzymes of Sulfatides arylsulfatase A and galactosylceramidase were significantly increased. In a Hepa1–6 murine liver cell line, indoxyl sulfate addition caused intracellular levels of Sulfatides to decrease and degradative enzymes of Sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of Sulfatides in the liver to decrease serum Sulfatide levels. One explanation of these results is that indoxyl sulfate, a uremic toxin, accelerates the degradation of Sulfatides in liver tissue.
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age dependent pparα activation induces hepatic Sulfatide accumulation in transgenic mice carrying the hepatitis c virus core gene
Glycoconjugate Journal, 2016Co-Authors: Yangyang Tian, Takero Nakajima, Yuji Kamijo, Yang Yang, Xiaowei Zhang, Naoki Tanaka, Eiko Sugiyama, Yu Lu, Kyoji Moriya, Kazuhiko KoikeAbstract:Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of Sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPARα activation and carcinogenesis in liver. However, the metabolism of Sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between Sulfatide metabolism, carcinogenesis, HCVcp, and PPARα, age-dependent changes of these factors were examined in HCVcpTg, PPARα inhibitor-treated HCVcpTg, and non-Tg mice. The Sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in Sulfatide synthesis, the hepatic expression of known Sulfatide-transferring protein, oxidative stress, and hepatic PPARα expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of Sulfatides and PPARα activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPARα inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPARα activation increases synthesis of Sulfatides and the resulting Sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic Sulfatide content and the modulation of Sulfatide generation by intervention using a PPARα inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively.
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chronic ethanol consumption decreases serum Sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice
Archives of Toxicology, 2014Co-Authors: Hiroki Kanbe, Takero Nakajima, Yuji Kamijo, Naoki Tanaka, Eiko Sugiyama, Lixuan Wang, Zhongze Fang, Atsushi HaraAbstract:Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver Sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver Sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum Sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum Sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.
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attenuation of kidney injuries maintains serum Sulfatide levels dependent on hepatic synthetic ability a possible involvement of oxidative stress
Tohoku Journal of Experimental Medicine, 2012Co-Authors: Takero Nakajima, Yuji Kamijo, Xiaowei Zhang, Xiaona Sheng, Lixuan Wang, Kyoko TakahashiAbstract:Serum Sulfatides are the major glycosphingolipids in lipoproteins. Although serum Sulfatides are mainly synthesized and secreted by the liver, they are significantly decreased when the kidneys are impaired. Our recent experimental study using a murine protein-overload nephropathy model suggested a hypothetical mechanism whereby serum Sulfatides were reduced due to kidney dysfunction. This was the result of decreased hepatic expression of a Sulfatide synthetic enzyme, cerebroside sulfotransferase (CST), which is associated with systemic enhancement of oxidative stress. However, there is a possibility that the experimental process, protein-overload itself, directly affected the Sulfatide metabolism and oxidative stress in the liver. To determine whether kidney dysfunction actually reduces the hepatic synthesis of Sulfatides via oxidative stress, we examined Sulfatide levels, the hepatic content of metabolic Sulfatide enzymes, and the degree of oxidative stress in protein-overload mice subjected to renoprotective therapy using clofibrate, a representative hypolipidemic medicine. Protein-overload mice exhibited marked kidney injuries, enhancement of hepatic oxidative stress, decreased levels of serum and hepatic Sulfatides, and decreased expression of hepatic CST. The clofibrate treatment attenuated kidney damage and hepatic oxidative stress while maintaining serum/hepatic Sulfatide levels and hepatic CST content in the mice. Because clofibrate monotherapy without protein-overload treatment only minimally affected these hepatic parameters, the hepatic synthesis of Sulfatides appeared to be strongly influenced by kidney dysfunction and subsequent oxidative stress. This study suggests that the crosstalk between kidney dysfunction and hepatic Sulfatide metabolism is mediated by oxidative stress. These results should help to understand the phenomenon in patients with end-stage kidney disease.
Takero Nakajima - One of the best experts on this subject based on the ideXlab platform.
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Effects of hypertension and antihypertensive treatments on Sulfatide levels in serum and its metabolism
Hypertension Research, 2019Co-Authors: Xiao Hu, Yosuke Yamada, Makoto Harada, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids present in lipoproteins that work as modulators of thrombosis and hemostasis. Decreased serum Sulfatide levels are suggested by our previous work to be related to cardiovascular disease (CVD). Hypertension, known to be an important risk factor for CVD, may affect serum Sulfatide levels. However, how hypertension affects serum Sulfatides directly and mechanistically is unknown. To elucidate these possible mechanisms, we investigated changes in serum Sulfatide levels and their metabolism using an established experimental model of hypertension that uses continuous infusion of angiotensin II (AngII) into mice. Furthermore, we also examined the effects of four different antihypertensive drugs (losartan, irbesartan, nifedipine, and hydralazine) on serum Sulfatide metabolism. Serum levels of Sulfatides were found to be decreased in groups in which only hypertension was induced (AngII only), whereas they were increased in groups with reduced blood pressure (antihypertensives only) and ameliorated to increasingly normal levels in groups with induced hypertension that were also treated (AngII+antihypertensives). Changes in serum Sulfatides were strongly related to hepatic expression levels of cerebroside sulfotransferase (CST), which is a key enzyme involved in Sulfatide synthesis. Furthermore, the current study suggests that the primary factors affecting CST expression are oxidative stress, peroxisome proliferator-activated receptor α activity and blood pressure itself. This study demonstrates that hypertension significantly decreases levels of serum Sulfatides by reducing hepatic CST expression via various effects mediated by AngII. Antihypertensive treatments can ameliorate abnormalities in serum Sulfatide levels and may partially prevent hypertension related CVD by positively affecting Sulfatide metabolism.
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Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice
Glycoconjugate Journal, 2019Co-Authors: Yosuke Yamada, Makoto Harada, Koji Hashimoto, Ran Guo, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids that are present in lipoproteins and exert anticoagulant effects. A previous study reported decreased levels of serum Sulfatides in hemodialysis patients and suggested an association with cardiovascular disease. However, the mechanism of changes in serum Sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a chronic kidney disease (CKD) state could decrease serum Sulfatide levels using 5/6 nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished Sulfatides. 5/6NCKD mice and sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum Sulfatide levels. Hepatic Sulfatide content, which is the origin of serum Sulfatides, and the expression of Sulfatide metabolic enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum creatinine and indoxyl sulfate. The serum levels and hepatic amounts of Sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative enzymes of Sulfatides arylsulfatase A and galactosylceramidase were significantly increased. In a Hepa1–6 murine liver cell line, indoxyl sulfate addition caused intracellular levels of Sulfatides to decrease and degradative enzymes of Sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of Sulfatides in the liver to decrease serum Sulfatide levels. One explanation of these results is that indoxyl sulfate, a uremic toxin, accelerates the degradation of Sulfatides in liver tissue.
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age dependent pparα activation induces hepatic Sulfatide accumulation in transgenic mice carrying the hepatitis c virus core gene
Glycoconjugate Journal, 2016Co-Authors: Yangyang Tian, Takero Nakajima, Yuji Kamijo, Yang Yang, Xiaowei Zhang, Naoki Tanaka, Eiko Sugiyama, Yu Lu, Kyoji Moriya, Kazuhiko KoikeAbstract:Sulfatides, a type of glycosphingolipid, are associated with carcinogenesis. Peroxisome proliferator-activated receptor α (PPARα) is involved in the regulation of Sulfatide metabolism as well as in cancer development. We previously reported that transgenic (Tg) mice expressing hepatitis C virus core protein (HCVcp) exhibited age-dependent PPARα activation and carcinogenesis in liver. However, the metabolism of Sulfatides in hepatocellular carcinoma is unknown. To examine the relationship between Sulfatide metabolism, carcinogenesis, HCVcp, and PPARα, age-dependent changes of these factors were examined in HCVcpTg, PPARα inhibitor-treated HCVcpTg, and non-Tg mice. The Sulfatide content in liver, the hepatic expression of two key enzymes catalyzing the initial and last reactions in Sulfatide synthesis, the hepatic expression of known Sulfatide-transferring protein, oxidative stress, and hepatic PPARα expression and its activation were age-dependently increased in HCVcpTg mice. The increased synthesis and accumulation of Sulfatides and PPARα activation were significantly enhanced in liver cancer lesions. These changes were attenuated by PPARα inhibitor treatment and not observed in non-Tg mice. These results suggest that HCVcp-induced age-dependent PPARα activation increases synthesis of Sulfatides and the resulting Sulfatide accumulation affects HCV-related liver cancer. The monitoring of hepatic Sulfatide content and the modulation of Sulfatide generation by intervention using a PPARα inhibitor might be useful for the prediction and prevention of HCV-related hepatocarcinogenesis, respectively.
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chronic ethanol consumption decreases serum Sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice
Archives of Toxicology, 2014Co-Authors: Hiroki Kanbe, Takero Nakajima, Yuji Kamijo, Naoki Tanaka, Eiko Sugiyama, Lixuan Wang, Zhongze Fang, Atsushi HaraAbstract:Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver Sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver Sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum Sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum Sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.
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attenuation of kidney injuries maintains serum Sulfatide levels dependent on hepatic synthetic ability a possible involvement of oxidative stress
Tohoku Journal of Experimental Medicine, 2012Co-Authors: Takero Nakajima, Yuji Kamijo, Xiaowei Zhang, Xiaona Sheng, Lixuan Wang, Kyoko TakahashiAbstract:Serum Sulfatides are the major glycosphingolipids in lipoproteins. Although serum Sulfatides are mainly synthesized and secreted by the liver, they are significantly decreased when the kidneys are impaired. Our recent experimental study using a murine protein-overload nephropathy model suggested a hypothetical mechanism whereby serum Sulfatides were reduced due to kidney dysfunction. This was the result of decreased hepatic expression of a Sulfatide synthetic enzyme, cerebroside sulfotransferase (CST), which is associated with systemic enhancement of oxidative stress. However, there is a possibility that the experimental process, protein-overload itself, directly affected the Sulfatide metabolism and oxidative stress in the liver. To determine whether kidney dysfunction actually reduces the hepatic synthesis of Sulfatides via oxidative stress, we examined Sulfatide levels, the hepatic content of metabolic Sulfatide enzymes, and the degree of oxidative stress in protein-overload mice subjected to renoprotective therapy using clofibrate, a representative hypolipidemic medicine. Protein-overload mice exhibited marked kidney injuries, enhancement of hepatic oxidative stress, decreased levels of serum and hepatic Sulfatides, and decreased expression of hepatic CST. The clofibrate treatment attenuated kidney damage and hepatic oxidative stress while maintaining serum/hepatic Sulfatide levels and hepatic CST content in the mice. Because clofibrate monotherapy without protein-overload treatment only minimally affected these hepatic parameters, the hepatic synthesis of Sulfatides appeared to be strongly influenced by kidney dysfunction and subsequent oxidative stress. This study suggests that the crosstalk between kidney dysfunction and hepatic Sulfatide metabolism is mediated by oxidative stress. These results should help to understand the phenomenon in patients with end-stage kidney disease.
Atsushi Hara - One of the best experts on this subject based on the ideXlab platform.
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chronic ethanol consumption decreases serum Sulfatide levels by suppressing hepatic cerebroside sulfotransferase expression in mice
Archives of Toxicology, 2014Co-Authors: Hiroki Kanbe, Takero Nakajima, Yuji Kamijo, Naoki Tanaka, Eiko Sugiyama, Lixuan Wang, Zhongze Fang, Atsushi HaraAbstract:Epidemiological studies demonstrate a possible relationship between chronic ethanol drinking and thrombotic diseases, such as myocardial infarction and stroke. However, the precise mechanism for this association remains unclear. Sulfatides are endogenous glycosphingolipids composed of ceramide, galactose, and sulfate, known to have anti-thrombotic properties. Low (0.5 g/kg/day), middle (1.5 g/kg/day), and high (3.0 g/kg/day) doses of ethanol were administered for 21 days intraperitoneally to female wild-type mice, and serum/liver Sulfatide levels were measured. No significant changes in cholesterol and triglycerides were seen in serum and liver by ethanol treatment. However, serum/liver Sulfatide levels were significantly decreased by middle- and high-dose ethanol treatment, likely due to downregulation of hepatic cerebroside sulfotransferase (CST) levels. Marked decreases in the expression of catalase and superoxide dismutases and ensuing increases in lipid peroxides were also observed in the livers of mice with middle- and high-dose ethanol treatment, suggesting the association between the suppression of hepatic CST expression and enhancement of oxidative stress. Furthermore, serum levels of tissue factor, a typical pro-coagulant molecule, were significantly increased in the mice with middle- and high-dose ethanol treatment showing decreases in serum Sulfatide levels. Collectively, these results demonstrate that chronic ethanol consumption reduces serum Sulfatide levels by increasing oxidative stress and decreasing the expression of CST in the liver. These findings could provide a mechanism by which chronic ethanol drinking increases thrombotic events.
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kidney transplantation recovers the reduction level of serum Sulfatide in esrd patients via processes correlated to oxidative stress and platelet count
Glycoconjugate Journal, 2011Co-Authors: Mamoru Kyogashima, Takero Nakajima, Toshifumi Aoyama, Yuji Kamijo, Lixuan Wang, Reiji Kannagi, Akihiro Matsumoto, Makoto Higuchi, Atsushi HaraAbstract:Sulfatide is a major component of glycosphingolipids in lipoproteins. Recently, we reported that a low serum level of Sulfatide in hemodialysis patients might be related to the high incidence of cardiovascular diseases. However, the serum kinetics of Sulfatide in kidney disease patients and the function of endogenous serum Sulfatide are still unclear. To obtain novel knowledge concerning these issues, we investigated the serum kinetics of Sulfatide in 5 adult kidney transplant recipients. We also analyzed the correlated factors influencing the serum Sulfatide level, using multiple regression analysis. Kidney transplantation caused a dramatic increase of serum Sulfatide without an alteration of its composition in all recipients in a time-dependent manner; however, the recovery speed was slower than that of the improvement of kidney function and the serum Sulfatide reached a nearly normal level after 1 year. Multiple regression analysis showed that the significant correlated factor influencing the serum Sulfatide level was log duration (time parameter) throughout the observation period, and the correlated factors detected in the stable phase were the decrease of serum concentration of malondialdehyde (an oxidative stress marker) as well as the elevation of platelet count. The current study results demonstrated the gradual but reliable recovery of the serum Sulfatide level in kidney transplant recipients for the first time, suggesting a close correlation between serum Sulfatide and kidney function. The recovery of serum Sulfatide might derive from the attenuation of systemic oxidative stress. The normal level of serum Sulfatide in kidney transplant recipients might affect platelet function, and contribute to the reduction of cardiovascular disease incidence.
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Sulfatides are associated with neointimal thickening after vascular injury
Atherosclerosis, 2010Co-Authors: Teruo Inoue, Takero Nakajima, Toshifumi Aoyama, Isao Taguchi, Gang Li, Rui Hu, Atsushi Hara, Reiji Kannagi, Mamoru KyogashimaAbstract:Abstract Background Sulfatides are known to be a native ligand of P-selectin. Platelet-leukocyte interaction via the cross-talk between P-selectin and Mac-1 (CD11b/CD18) plays an important role in the mechanism of neointimal thickening after vascular injury such as that seen in post-stent restenosis. However, the roles of Sulfatides on restenosis have not been elucidated. Methods Serum Sulfatide levels, P-selectin expression on the surface of platelets, and activated Mac-1 on the surface of neutrophils were serially measured using both coronary sinus and peripheral blood samples in 21 patients who underwent coronary stent implantation. Results The trans-cardiac gradient (coronary sinus minus peripheral blood) of the Sulfatide levels significantly increased at 15min (−1.47±2.87 to 0.59±1.44nmol/ml, p p p p p p Conclusions Sulfatides may play a physiological role on inflammation in vascular injury and the development of neointimal thickening.
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rapid demonstration of diversity of Sulfatide molecular species from biological materials by maldi tof ms
Glycobiology, 2006Co-Authors: Mamoru Kyogashima, Toshifumi Aoyama, Gang Li, Rui Hu, Atsushi Hara, Keiko Tamiyakoizumi, Takashi Ehara, Reiji KannagiAbstract:: By combining the partition method for enrichment of Sulfatides without any chromatographic procedures and the preparation method of lysoSulfatides, we succeeded in analyzing these sulfated glycosphingolipids from biological materials by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to reduce the complexity of mass fragmentation patterns within a day. We found that sulfated GalCer (HSO3-3Gal beta 1Cer) (SM4s [galactosylSulfatide]) was composed of different species. While composition of SM4s specifically depended on source materials, it always contained hydroxy fatty acids of various degrees. In addition to the common sphingoid 4-sphingenine (d18:1), uncommon/unusual sphingoids phytosphingosine (4-hydroxysphinganine) (t18:0), eicosasphinganine (d20:0), 4-eicosasphingenine (d20:1), and sphingadienine (d18:2) were easily detected. Finally, in addition to SM4s, Sulfatide sulfated LacCer (HSO3-3Gal beta 4Glc beta 1Cer) (SM3 [sulfated lactosylceramide]) and sulfated Gg3Cer (GalNAc beta 4(HSO3-3)Gal beta 4Glc beta 1Cer) (SM2 [sulfated gangliotriaosylceramide]) were clearly detected in renal tubule cells. The major SM4s was composed of ceramides possessing d18:1 with C22 hydroxy fatty acids (C22:0 h), C23:0 h, and C24:0 h, whereas the major SM3/SM2 were composed of ceramides possessing t18:0 with C22 normal fatty acids (C22:0), C23:0, C24:0. Namely, in these two series of Sulfatides, either fatty acids or sphingoids were hydroxylated, and chain lengths of these components were exactly the same, consequently resulting in a similar polarity of ceramide moieties in these Sulfatide species. These results demonstrated diversities of Sulfatide molecular species, not only with respect to sugar moieties but also to ceramide moieties, which are probably important for specific effective functions in particular microenvironments such as lipid membrane microdomains.
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Contradictory functions of Sulfatide in the blood coagulation system as coagulant and anticoagulant
Acta Biochimica Polonica, 1998Co-Authors: Mamoru Kyogashima, Atsushi Hara, Junichi Onaya, Tamotsu TaketomiAbstract:Sulfatide (galactosylceramide I3 -sulfate) has been reported to activate blood coagulation factor XII (Hageman factor), which suggests that it exhibits coagulant activity (Fujikama et al., 1980 Biochemistry 19, 1322-1330) However, Sulfatide administered into animals as a bolus shot without subsequent thrombus formation, prolonged conventional clotting times and bleeding time (Hara et al., 1996 Glycoconjugate J. 13, 187-194). These findings suggest that it may exhibit anticoagulant rather than coagulant activity. Following this suggestion we found in vitro that binding of Sulfatide to fibrinogen resulted in disturbance of fibrin formation. To examine a possible pharmacological effect of Sulfatide on blood coagulation in vivo we continuously infused Sulfatide into rats through plastic cannulae and found formation of giant thrombi around the tips of the cannulae. These data suggest that Sulfatide may exhibit contradictory functions in the blood coagulation system.
Y. Zhang - One of the best experts on this subject based on the ideXlab platform.
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Synthetic sulfogalactosylceramide (Sulfatide) and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies.
Glycoconjugate Journal, 2008Co-Authors: Y. Curi,, B. Colsh,, Carlos Afonso, N. Baumann,, J. C. Tabet,, Jean-maurice Mallet, Y. ZhangAbstract:3-O-Sulfogalactosylceramides (Sulfatides) accumulate in the genetic disease metachromatic leukodystrophy which is due to a defect in the catabolic enzyme, arylsulfatase A. Clinical diagnosis is usually confirmed by in vitro enzymatic deficiency of arylsulfatase A activity. The diagnosis may be complicated because of arylsulfatase A pseudo-deficiencies and another cause of MLD, sphingolipid activator B deficiency. As large quantities of Sulfatides can be found in the urine in this disease, sulfatiduria appears as an extremely useful test. As recently enzyme replacement is underway, the quantitative determination, using an internal standard, appears particularly useful as a follow-up. Thus a non-physiological Sulfatide was synthesized for this purpose, i.e. 3-O-sulfo-beta-D-C17 galactosylceramide (3-O-Sulfo-D: -Galactosyl-beta1'-->1-N-Heptadecanoyl-D-erythro-Sphingosine). It has been prepared through condensation of an azidosphingosine derivative with a protected D-galactopyranosyltrichloroacetimidate. Reduction of the azide was followed by acylation of a C-17 fatty acid. The key step was achieved by selective sulfation of the desired hydroxyl group on the sugar residue of the galactosylceramide using the stannylene methodology to give a 3'-sulfated beta-galactosyl C-17 ceramide.
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synthetic sulfogalactosylceramide Sulfatide and its use for the mass spectrometric quantitative urinary determination in metachromatic leukodystrophies
Glycoconjugate Journal, 2008Co-Authors: Benoit Colsch, Carlos Afonso, N. Baumann,, J. C. Tabet,, Jean-maurice Mallet, Y. ZhangAbstract:3-O-Sulfogalactosylceramides (Sulfatides) accumulate in the genetic disease metachromatic leukodystrophy which is due to a defect in the catabolic enzyme, arylsulfatase A. Clinical diagnosis is usually confirmed by in vitro enzymatic deficiency of arylsulfatase A activity. The diagnosis may be complicated because of arylsulfatase A pseudo-deficiencies and another cause of MLD, sphingolipid activator B deficiency. As large quantities of Sulfatides can be found in the urine in this disease, sulfatiduria appears as an extremely useful test. As recently enzyme replacement is underway, the quantitative determination, using an internal standard, appears particularly useful as a follow-up. Thus a non-physiological Sulfatide was synthesized for this purpose, i.e. 3-O-sulfo-β-d-C17 galactosylceramide (3-O-Sulfo-d-Galactosyl-β1′→1-N-Heptadecanoyl-d-erythro-Sphingosine). It has been prepared through condensation of an azidosphingosine derivative with a protected d-galactopyranosyltrichloroacetimidate. Reduction of the azide was followed by acylation of a C-17 fatty acid. The key step was achieved by selective sulfation of the desired hydroxyl group on the sugar residue of the galactosylceramide using the stannylene methodology to give a 3′-sulfated beta-galactosyl C-17 ceramide.
Toshifumi Aoyama - One of the best experts on this subject based on the ideXlab platform.
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Effects of hypertension and antihypertensive treatments on Sulfatide levels in serum and its metabolism
Hypertension Research, 2019Co-Authors: Xiao Hu, Yosuke Yamada, Makoto Harada, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids present in lipoproteins that work as modulators of thrombosis and hemostasis. Decreased serum Sulfatide levels are suggested by our previous work to be related to cardiovascular disease (CVD). Hypertension, known to be an important risk factor for CVD, may affect serum Sulfatide levels. However, how hypertension affects serum Sulfatides directly and mechanistically is unknown. To elucidate these possible mechanisms, we investigated changes in serum Sulfatide levels and their metabolism using an established experimental model of hypertension that uses continuous infusion of angiotensin II (AngII) into mice. Furthermore, we also examined the effects of four different antihypertensive drugs (losartan, irbesartan, nifedipine, and hydralazine) on serum Sulfatide metabolism. Serum levels of Sulfatides were found to be decreased in groups in which only hypertension was induced (AngII only), whereas they were increased in groups with reduced blood pressure (antihypertensives only) and ameliorated to increasingly normal levels in groups with induced hypertension that were also treated (AngII+antihypertensives). Changes in serum Sulfatides were strongly related to hepatic expression levels of cerebroside sulfotransferase (CST), which is a key enzyme involved in Sulfatide synthesis. Furthermore, the current study suggests that the primary factors affecting CST expression are oxidative stress, peroxisome proliferator-activated receptor α activity and blood pressure itself. This study demonstrates that hypertension significantly decreases levels of serum Sulfatides by reducing hepatic CST expression via various effects mediated by AngII. Antihypertensive treatments can ameliorate abnormalities in serum Sulfatide levels and may partially prevent hypertension related CVD by positively affecting Sulfatide metabolism.
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Impact of chronic kidney dysfunction on serum Sulfatides and its metabolic pathway in mice
Glycoconjugate Journal, 2019Co-Authors: Yosuke Yamada, Makoto Harada, Koji Hashimoto, Ran Guo, Takero Nakajima, Toshihide Kashihara, Mitsuhiko Yamada, Toshifumi Aoyama, Yuji KamijoAbstract:Serum Sulfatides are critical glycosphingolipids that are present in lipoproteins and exert anticoagulant effects. A previous study reported decreased levels of serum Sulfatides in hemodialysis patients and suggested an association with cardiovascular disease. However, the mechanism of changes in serum Sulfatides in chronic kidney dysfunction has not been well investigated. The current study examined whether a chronic kidney disease (CKD) state could decrease serum Sulfatide levels using 5/6 nephrectomy (5/6NCKD) mice, an established CKD murine model, and studied the mechanisms contributing to diminished Sulfatides. 5/6NCKD mice and sham operation control mice were sacrificed at the 4th or 12th postoperative week (POW) for measurement of serum Sulfatide levels. Hepatic Sulfatide content, which is the origin of serum Sulfatides, and the expression of Sulfatide metabolic enzymes in liver tissue were assessed as well. The 5/6NCKD mice developed CKD and showed increased serum creatinine and indoxyl sulfate. The serum levels and hepatic amounts of Sulfatides were significantly decreased in 5/6NCKD mice at both 4 and 12 POW, while the degradative enzymes of Sulfatides arylsulfatase A and galactosylceramidase were significantly increased. In a Hepa1–6 murine liver cell line, indoxyl sulfate addition caused intracellular levels of Sulfatides to decrease and degradative enzymes of Sulfatides to increase in a manner comparable to the changes in 5/6NCKD mice liver tissue. In conclusion, chronic kidney dysfunction causes degradation of Sulfatides in the liver to decrease serum Sulfatide levels. One explanation of these results is that indoxyl sulfate, a uremic toxin, accelerates the degradation of Sulfatides in liver tissue.
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kidney transplantation recovers the reduction level of serum Sulfatide in esrd patients via processes correlated to oxidative stress and platelet count
Glycoconjugate Journal, 2011Co-Authors: Mamoru Kyogashima, Takero Nakajima, Toshifumi Aoyama, Yuji Kamijo, Lixuan Wang, Reiji Kannagi, Akihiro Matsumoto, Makoto Higuchi, Atsushi HaraAbstract:Sulfatide is a major component of glycosphingolipids in lipoproteins. Recently, we reported that a low serum level of Sulfatide in hemodialysis patients might be related to the high incidence of cardiovascular diseases. However, the serum kinetics of Sulfatide in kidney disease patients and the function of endogenous serum Sulfatide are still unclear. To obtain novel knowledge concerning these issues, we investigated the serum kinetics of Sulfatide in 5 adult kidney transplant recipients. We also analyzed the correlated factors influencing the serum Sulfatide level, using multiple regression analysis. Kidney transplantation caused a dramatic increase of serum Sulfatide without an alteration of its composition in all recipients in a time-dependent manner; however, the recovery speed was slower than that of the improvement of kidney function and the serum Sulfatide reached a nearly normal level after 1 year. Multiple regression analysis showed that the significant correlated factor influencing the serum Sulfatide level was log duration (time parameter) throughout the observation period, and the correlated factors detected in the stable phase were the decrease of serum concentration of malondialdehyde (an oxidative stress marker) as well as the elevation of platelet count. The current study results demonstrated the gradual but reliable recovery of the serum Sulfatide level in kidney transplant recipients for the first time, suggesting a close correlation between serum Sulfatide and kidney function. The recovery of serum Sulfatide might derive from the attenuation of systemic oxidative stress. The normal level of serum Sulfatide in kidney transplant recipients might affect platelet function, and contribute to the reduction of cardiovascular disease incidence.
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Sulfatides are associated with neointimal thickening after vascular injury
Atherosclerosis, 2010Co-Authors: Teruo Inoue, Takero Nakajima, Toshifumi Aoyama, Isao Taguchi, Gang Li, Rui Hu, Atsushi Hara, Reiji Kannagi, Mamoru KyogashimaAbstract:Abstract Background Sulfatides are known to be a native ligand of P-selectin. Platelet-leukocyte interaction via the cross-talk between P-selectin and Mac-1 (CD11b/CD18) plays an important role in the mechanism of neointimal thickening after vascular injury such as that seen in post-stent restenosis. However, the roles of Sulfatides on restenosis have not been elucidated. Methods Serum Sulfatide levels, P-selectin expression on the surface of platelets, and activated Mac-1 on the surface of neutrophils were serially measured using both coronary sinus and peripheral blood samples in 21 patients who underwent coronary stent implantation. Results The trans-cardiac gradient (coronary sinus minus peripheral blood) of the Sulfatide levels significantly increased at 15min (−1.47±2.87 to 0.59±1.44nmol/ml, p p p p p p Conclusions Sulfatides may play a physiological role on inflammation in vascular injury and the development of neointimal thickening.
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rapid demonstration of diversity of Sulfatide molecular species from biological materials by maldi tof ms
Glycobiology, 2006Co-Authors: Mamoru Kyogashima, Toshifumi Aoyama, Gang Li, Rui Hu, Atsushi Hara, Keiko Tamiyakoizumi, Takashi Ehara, Reiji KannagiAbstract:: By combining the partition method for enrichment of Sulfatides without any chromatographic procedures and the preparation method of lysoSulfatides, we succeeded in analyzing these sulfated glycosphingolipids from biological materials by matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOF MS) to reduce the complexity of mass fragmentation patterns within a day. We found that sulfated GalCer (HSO3-3Gal beta 1Cer) (SM4s [galactosylSulfatide]) was composed of different species. While composition of SM4s specifically depended on source materials, it always contained hydroxy fatty acids of various degrees. In addition to the common sphingoid 4-sphingenine (d18:1), uncommon/unusual sphingoids phytosphingosine (4-hydroxysphinganine) (t18:0), eicosasphinganine (d20:0), 4-eicosasphingenine (d20:1), and sphingadienine (d18:2) were easily detected. Finally, in addition to SM4s, Sulfatide sulfated LacCer (HSO3-3Gal beta 4Glc beta 1Cer) (SM3 [sulfated lactosylceramide]) and sulfated Gg3Cer (GalNAc beta 4(HSO3-3)Gal beta 4Glc beta 1Cer) (SM2 [sulfated gangliotriaosylceramide]) were clearly detected in renal tubule cells. The major SM4s was composed of ceramides possessing d18:1 with C22 hydroxy fatty acids (C22:0 h), C23:0 h, and C24:0 h, whereas the major SM3/SM2 were composed of ceramides possessing t18:0 with C22 normal fatty acids (C22:0), C23:0, C24:0. Namely, in these two series of Sulfatides, either fatty acids or sphingoids were hydroxylated, and chain lengths of these components were exactly the same, consequently resulting in a similar polarity of ceramide moieties in these Sulfatide species. These results demonstrated diversities of Sulfatide molecular species, not only with respect to sugar moieties but also to ceramide moieties, which are probably important for specific effective functions in particular microenvironments such as lipid membrane microdomains.
