The Experts below are selected from a list of 223902 Experts worldwide ranked by ideXlab platform
Makoto Miyazaki - One of the best experts on this subject based on the ideXlab platform.
-
the cdk9 cyclin t1 complex mediates Saturated Fatty Acid induced vascular calcification by inducing expression of the transcription factor chop
Journal of Biological Chemistry, 2018Co-Authors: Yuji Shiozaki, Shinobu Miyazakianzai, Kayo Okamura, Shohei Kohno, Audrey L Keena, Kristina L Williams, Xiaoyu Zhao, Wallace S Chick, Makoto MiyazakiAbstract:Vascular calcification (or mineralization) is a common complication of chronic kidney disease (CKD) and is closely associated with increased mortality and morbidity rates. We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the Saturated Fatty Acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Here, using mouse models of CKD, we 1) studied the contribution of the proapoptotic transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) to CKD-dependent medial calcification, and 2) we identified an additional regulator of ER stress-mediated CHOP expression. Transgenic mice having smooth muscle cell (SMC)-specific CHOP expression developed severe vascular apoptosis and medial calcification under CKD. Screening of a protein kinase inhibitor library identified 16 compounds, including seven cyclin-dependent kinase (CDK) inhibitors, that significantly suppressed CHOP induction during ER stress. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Cyclin T1 knockout inhibited SFA-mediated induction of CHOP and mineralization, whereas deletion of cyclin T2 and cyclin K promoted CHOP expression levels and mineralization. Of note, the CDK9-cyclin T1 complex directly phosphorylated and activated ATF4. These results demonstrate that the CDK9-cyclin T1 and CDK9-cyclin T2/K complexes have opposing roles in CHOP expression and CKD-induced vascular calcification. They further reveal that the CDK9-cyclin T1 complex mediates vascular calcification through CHOP induction and phosphorylation-mediated ATF4 activation.
-
Saturated phosphatidic Acids mediate Saturated Fatty Acid induced vascular calcification and lipotoxicity
Journal of Clinical Investigation, 2015Co-Authors: Masashi Masuda, Shinobu Miyazakianzai, Audrey L Keenan, Jessica Kendrick, Kayo Okamura, Stefan Offermanns, Makoto Kuroo, Michel Chonchol, JAMES MUKASA NTAMBI, Makoto MiyazakiAbstract:Abstract Recent evidence indicates that Saturated Fatty Acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unSaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully Saturated phosphatidic Acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.
Jacques Jose - One of the best experts on this subject based on the ideXlab platform.
-
experimental vapor pressures from 1 pa to 100 kpa of six Saturated Fatty Acid methyl esters fames methyl hexanoate methyl octanoate methyl decanoate methyl dodecanoate methyl tetradecanoate and methyl hexadecanoate
The Journal of Chemical Thermodynamics, 2016Co-Authors: Kamel Khimeche, Ilham Mokbel, Abdallah Dahmani, Lakhda Sahraoui, Jacques JoseAbstract:Abstract Vapor pressures of six Saturated Fatty Acid Methyl Esters (FAMEs), methyl hexanoate (or methyl caproate), methyl octanoate (or methyl caprylate), Methyl decanoate (or methyl caprate), methyl dodecanoate (or methyl laurate), methyl tetradecanoate (or methyl myristate), and methyl hexadecanoate (or methyl palmitate) were measured from 1 Pa to 100 kPa and at temperature range between 262 and 453 K using a static apparatus. The experimental data (P-T) were compared with the available literature data.
-
experimental vapor pressures of five Saturated Fatty Acid ethyl ester faee components of biodiesel
Journal of Chemical & Engineering Data, 2011Co-Authors: Mokhta Enziane, Kamel Khimeche, Ilham Mokbel, Terufa Sawaya, Abdallah Dahmani, Jacques JoseAbstract:Vapor pressures of five Saturated Fatty Acid ethyl esters (FAEEs), ethyl hexanoate (or ethyl caproate), ethyl octanoate (or ethyl caprylate), ethyl decanoate (or ethyl caprate), ethyl dodecanoate (or ethyl laurate), and ethyl tetradecanoate (or ethyl myristate), were measured at pressures from 1 Pa to 180 kPa and temperatures from (253.15 to 463.15) K using a static apparatus. These esters are a light fraction present in biodiesel derived from palmist oil and copra oil (Ballerini and Alazard-Toux, Les biocarburants; IFP Publications: Paris, 2006). The experimental data (P–T) were smoothed using the Antoine equation and compared with the available literature values. The molar enthalpies of vaporization at the mean temperature of the experimental range were derived from the Clausius–Clapeyron equation. From these results the standard enthalpies of vaporization at T = 298.15 K were calculated.
Michael J Pagliassotti - One of the best experts on this subject based on the ideXlab platform.
-
Reduced endoplasmic reticulum luminal calcium links Saturated Fatty Acid-mediated endoplasmic reticulum stress and cell death in liver cells
Molecular and Cellular Biochemistry, 2009Co-Authors: Dong Wang, Christopher L. Gentile, Michael J PagliassottiAbstract:Chronic exposure to elevated free Fatty Acids, in particular long chain Saturated Fatty Acids, provokes endoplasmic reticulum (ER) stress and cell death in a number of cell types. The perturbations to the ER that instigate ER stress and activation of the unfolded protein in response to Fatty Acids in hepatocytes have not been identified. The present study employed H4IIE liver cells and primary rat hepatocytes to examine the hypothesis that Saturated Fatty Acids induce ER stress via effects on ER luminal calcium stores. Exposure of H4IIE liver cells and primary hepatocytes to palmitate and stearate reduced thapsigargin-sensitive calcium stores and increased biochemical markers of ER stress over similar time courses (6 h). These changes preceded cell death, which was only observed at later time points (16 h). Co-incubation with oleate prevented the reduction in calcium stores, induction of ER stress markers and cell death observed in response to palmitate. Inclusion of calcium chelators, BAPTA-AM or EGTA, reduced palmitate- and stearate-mediated enrichment of cytochrome c in post-mitochondrial supernatant fractions and cell death. These data suggest that redistribution of ER luminal calcium contributes to long chain Saturated Fatty Acid-mediated ER stress and cell death.
-
Saturated Fatty Acid mediated endoplasmic reticulum stress and apoptosis are augmented by trans 10 cis 12 conjugated linoleic Acid in liver cells
Molecular and Cellular Biochemistry, 2007Co-Authors: Yure Wei, Dong Wang, Michael J PagliassottiAbstract:Lipid accumulation in non-adipose tissues leads to cell dysfunction and apoptosis, a phenomenon known as lipotoxicity. Recent evidence suggests that lipotoxicity in hepatocytes involves endoplasmic reticulum (ER) stress and c-Jun NH2-terminal kinase-mediated apoptosis. The present study examined (1) the dose–response and time course characteristics of Fatty Acid-mediated ER stress and apoptosis in H4IIE liver cells; (2) whether Saturated Fatty Acid-induced apoptosis involved the ER-associated caspase-12; and (3) whether trans-10, cis-12-conjugated linoleic Acid, an inhibitor of stearoyl-CoA desaturase, influenced Fatty Acid-mediated ER stress and apoptosis. Saturated Fatty Acids induced ER stress in a dose-dependent manner with a time course that was delayed relative to chemical-induction of ER stress. Saturated Fatty Acids increased caspase-9 and caspase-3 activity, however increased caspase-12 activity was not observed. Inhibition of stearoyl-CoA desaturase, using conjugated linoleic Acid (trans-10, cis-12), augmented Saturated Fatty Acid-induced ER stress and apoptosis. These data suggest that Saturated Fatty Acids induce ER stress and apoptosis at physiologic concentrations and with a relatively rapid time course. It would appear that Saturated Fatty Acid-mediated apoptosis occurs independently of caspase-12 activation. Since conjugated linoleic Acid inhibited stearoyl-CoA desaturase activity, it is hypothesized that saturation, per se, plays a role in lipotoxicity in liver cells.
Ilham Mokbel - One of the best experts on this subject based on the ideXlab platform.
-
experimental vapor pressures from 1 pa to 100 kpa of six Saturated Fatty Acid methyl esters fames methyl hexanoate methyl octanoate methyl decanoate methyl dodecanoate methyl tetradecanoate and methyl hexadecanoate
The Journal of Chemical Thermodynamics, 2016Co-Authors: Kamel Khimeche, Ilham Mokbel, Abdallah Dahmani, Lakhda Sahraoui, Jacques JoseAbstract:Abstract Vapor pressures of six Saturated Fatty Acid Methyl Esters (FAMEs), methyl hexanoate (or methyl caproate), methyl octanoate (or methyl caprylate), Methyl decanoate (or methyl caprate), methyl dodecanoate (or methyl laurate), methyl tetradecanoate (or methyl myristate), and methyl hexadecanoate (or methyl palmitate) were measured from 1 Pa to 100 kPa and at temperature range between 262 and 453 K using a static apparatus. The experimental data (P-T) were compared with the available literature data.
-
experimental vapor pressures of five Saturated Fatty Acid ethyl ester faee components of biodiesel
Journal of Chemical & Engineering Data, 2011Co-Authors: Mokhta Enziane, Kamel Khimeche, Ilham Mokbel, Terufa Sawaya, Abdallah Dahmani, Jacques JoseAbstract:Vapor pressures of five Saturated Fatty Acid ethyl esters (FAEEs), ethyl hexanoate (or ethyl caproate), ethyl octanoate (or ethyl caprylate), ethyl decanoate (or ethyl caprate), ethyl dodecanoate (or ethyl laurate), and ethyl tetradecanoate (or ethyl myristate), were measured at pressures from 1 Pa to 180 kPa and temperatures from (253.15 to 463.15) K using a static apparatus. These esters are a light fraction present in biodiesel derived from palmist oil and copra oil (Ballerini and Alazard-Toux, Les biocarburants; IFP Publications: Paris, 2006). The experimental data (P–T) were smoothed using the Antoine equation and compared with the available literature values. The molar enthalpies of vaporization at the mean temperature of the experimental range were derived from the Clausius–Clapeyron equation. From these results the standard enthalpies of vaporization at T = 298.15 K were calculated.
Kayo Okamura - One of the best experts on this subject based on the ideXlab platform.
-
the cdk9 cyclin t1 complex mediates Saturated Fatty Acid induced vascular calcification by inducing expression of the transcription factor chop
Journal of Biological Chemistry, 2018Co-Authors: Yuji Shiozaki, Shinobu Miyazakianzai, Kayo Okamura, Shohei Kohno, Audrey L Keena, Kristina L Williams, Xiaoyu Zhao, Wallace S Chick, Makoto MiyazakiAbstract:Vascular calcification (or mineralization) is a common complication of chronic kidney disease (CKD) and is closely associated with increased mortality and morbidity rates. We recently reported that activation of the activating transcription factor 4 (ATF4) pathway through the Saturated Fatty Acid (SFA)-induced endoplasmic reticulum (ER) stress response plays a causative role in CKD-associated vascular calcification. Here, using mouse models of CKD, we 1) studied the contribution of the proapoptotic transcription factor CCAAT enhancer-binding protein homologous protein (CHOP) to CKD-dependent medial calcification, and 2) we identified an additional regulator of ER stress-mediated CHOP expression. Transgenic mice having smooth muscle cell (SMC)-specific CHOP expression developed severe vascular apoptosis and medial calcification under CKD. Screening of a protein kinase inhibitor library identified 16 compounds, including seven cyclin-dependent kinase (CDK) inhibitors, that significantly suppressed CHOP induction during ER stress. Moreover, selective CDK9 inhibitors and CRISPR/Cas9-mediated CDK9 reduction blocked SFA-mediated induction of CHOP expression, whereas inhibitors of other CDK isoforms did not. Cyclin T1 knockout inhibited SFA-mediated induction of CHOP and mineralization, whereas deletion of cyclin T2 and cyclin K promoted CHOP expression levels and mineralization. Of note, the CDK9-cyclin T1 complex directly phosphorylated and activated ATF4. These results demonstrate that the CDK9-cyclin T1 and CDK9-cyclin T2/K complexes have opposing roles in CHOP expression and CKD-induced vascular calcification. They further reveal that the CDK9-cyclin T1 complex mediates vascular calcification through CHOP induction and phosphorylation-mediated ATF4 activation.
-
Saturated phosphatidic Acids mediate Saturated Fatty Acid induced vascular calcification and lipotoxicity
Journal of Clinical Investigation, 2015Co-Authors: Masashi Masuda, Shinobu Miyazakianzai, Audrey L Keenan, Jessica Kendrick, Kayo Okamura, Stefan Offermanns, Makoto Kuroo, Michel Chonchol, JAMES MUKASA NTAMBI, Makoto MiyazakiAbstract:Abstract Recent evidence indicates that Saturated Fatty Acid-induced (SFA-induced) lipotoxicity contributes to the pathogenesis of cardiovascular and metabolic diseases; however, the molecular mechanisms that underlie SFA-induced lipotoxicity remain unclear. Here, we have shown that repression of stearoyl-CoA desaturase (SCD) enzymes, which regulate the intracellular balance of SFAs and unSaturated FAs, and the subsequent accumulation of SFAs in vascular smooth muscle cells (VSMCs), are characteristic events in the development of vascular calcification. We evaluated whether SMC-specific inhibition of SCD and the resulting SFA accumulation plays a causative role in the pathogenesis of vascular calcification and generated mice with SMC-specific deletion of both Scd1 and Scd2. Mice lacking both SCD1 and SCD2 in SMCs displayed severe vascular calcification with increased ER stress. Moreover, we employed shRNA library screening and radiolabeling approaches, as well as in vitro and in vivo lipidomic analysis, and determined that fully Saturated phosphatidic Acids such as 1,2-distearoyl-PA (18:0/18:0-PA) mediate SFA-induced lipotoxicity and vascular calcification. Together, these results identify a key lipogenic pathway in SMCs that mediates vascular calcification.
