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Kyozo Hayashi - One of the best experts on this subject based on the ideXlab platform.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich Alpha2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:Abstract The phospholipase A2(PLA2) inhibitor PLIβ, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527–531). In the present study, the 50-kDa subunit was found to be glycosylated withN-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIβ was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIβ. A cDNA encoding PLIβ was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potentialN-glycosylation sites. The sequence of PLIβ showed no significant homology with that of the known PLA2inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich α2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIβ might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich α2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:The phospholipase A2 (PLA2) inhibitor PLIbeta, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527-531). In the present study, the 50-kDa subunit was found to be glycosylated with N-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIbeta was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIbeta. A cDNA encoding PLIbeta was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potential N-glycosylation sites. The sequence of PLIbeta showed no significant homology with that of the known PLA2 inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich Alpha2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIbeta might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
Kohji Okumura - One of the best experts on this subject based on the ideXlab platform.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich Alpha2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:Abstract The phospholipase A2(PLA2) inhibitor PLIβ, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527–531). In the present study, the 50-kDa subunit was found to be glycosylated withN-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIβ was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIβ. A cDNA encoding PLIβ was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potentialN-glycosylation sites. The sequence of PLIβ showed no significant homology with that of the known PLA2inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich α2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIβ might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich α2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:The phospholipase A2 (PLA2) inhibitor PLIbeta, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527-531). In the present study, the 50-kDa subunit was found to be glycosylated with N-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIbeta was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIbeta. A cDNA encoding PLIbeta was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potential N-glycosylation sites. The sequence of PLIbeta showed no significant homology with that of the known PLA2 inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich Alpha2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIbeta might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
Chen Bing - One of the best experts on this subject based on the ideXlab platform.
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the adipokine zinc α2 Glycoprotein zag is downregulated with fat mass expansion in obesity
Clinical Endocrinology, 2010Co-Authors: Tomas Mracek, Paul Trayhurn, Theodora Tzanavari, Q Ding, Katarina Kos, Jonathan Pinkney, John P H Wilding, Chen BingAbstract:INTRODUCTION Zinc-Alpha2-Glycoprotein (ZAG) is a novel adipokine, which may act locally to influence adipocyte metabolism. This study assessed the effect of increased adiposity on ZAG expression in adipose tissue in human subjects. The study also examined the association between ZAG and adiponectin expression in human adipose tissue, and whether ZAG modulates adiponectin secretion by human adipocytes. METHODS Adipose tissue (visceral and subcutaneous) was collected from human subjects with a wide range of BMIs. Human Simpson-Golabi-Behmel syndrome (SGBS) adipocytes were used for in vitro studies. ZAG mRNA levels were quantified by real-time PCR and protein by Western blotting. RESULTS In human subjects, ZAG mRNA level was negatively correlated with BMI (r = -0.61, P < 0.001, n = 23, visceral; r = -0.6, P < 0.05, n = 14, subcutaneous) and fat mass (r = -0.62, P < 0.01, visceral; r = -0.6, P < 0.05, subcutaneous). Negative associations were also found between ZAG mRNA and insulin resistance parameters including plasma insulin (r = -0.65, P < 0.001, visceral; r = -0.55, P < 0.05, subcutaneous) and homeostasis model of insulin resistance (HOMA-IR) (r = -0.65, P < 0.001, visceral; r = -0.52, P = 0.055, subcutaneous), and C reactive protein (CRP) (r = -0.46, P < 0.05, visceral; r = -0.53, P < 0.05, subcutaneous). However, ZAG mRNA was positively correlated with adiponectin (r = 0.5, P < 0.05, visceral; r = 0.82, P < 0.001, subcutaneous) but negatively associated with leptin mRNA (r = -0.42, P < 0.05, visceral; r = -0.54, P < 0.05, subcutaneous). ZAG secretion by differentiated human adipocytes was abundant. Addition of recombinant ZAG stimulated adiponectin release from human adipocytes. CONCLUSION ZAG gene expression in adipose tissue is downregulated with increased adiposity and circulating insulin. ZAG mRNA is positively correlated with adiponectin mRNA, and ZAG enhances adiponectin production by human adipocytes. We suggest that ZAG is linked to obesity and obesity-related insulin resistance.
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downregulation of zinc α2 Glycoprotein in adipose tissue and liver of obese ob ob mice and by tumour necrosis factor α in adipocytes
Journal of Endocrinology, 2010Co-Authors: Tomas Mracek, Yi Bao, Paul Trayhurn, Dan Gao, Theodora Tzanavari, Xinhua Xiao, Claire J Stocker, Chen BingAbstract:Zinc-Alpha2-Glycoprotein (ZAG, also listed as AZGP1 in the MGI Database), a lipid-mobilising factor, has recently been suggested as a potential candidate in the modulation of body weight. We investigated the effect of increased adiposity on ZAG expression in adipose tissue and the liver and on plasma levels in obese (ob/ob) mice compared with lean siblings. The study also examined the effect of the pro-inflammatory cytokine tumour necrosis factor-alpha (TNFalpha) on ZAG expression in adipocytes. Zag mRNA levels were significantly reduced in subcutaneous (fourfold) and epididymal (eightfold) fat of ob/ob mice. Consistently, ZAG protein content was decreased in both fat depots of ob/ob mice. In the liver of obese animals, steatosis was accompanied by the fall of both Zag mRNA (twofold) and ZAG protein content (2.5-fold). Plasma ZAG levels were also decreased in obese mice. In addition, Zag mRNA was reduced in epididymal (fivefold) and retroperitoneal (fivefold) adipose tissue of obese (fa/fa) Zucker rats. In contrast to Zag expression, Tnfalpha mRNA levels were elevated in adipose tissue (twofold) and the liver (2.5-fold) of ob/ob mice. Treatment with TNFalpha reduced Zag gene expression in differentiated adipocytes, and this inhibition was chronic, occurring at 24 and 48 h following TNFalpha treatment. It is concluded that ZAG synthesis in adipose tissue and the liver is downregulated, as are its circulating levels, in ob/ob mice. The reduced ZAG production may advance the susceptibility to lipid accumulation in these tissues in obesity, and this could be at least in part attributable to the inhibitory effect of TNFalpha.
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zinc α2 Glycoprotein a lipid mobilizing factor is expressed in adipocytes and is up regulated in mice with cancer cachexia
Proceedings of the National Academy of Sciences of the United States of America, 2004Co-Authors: Chen Bing, Yi Bao, John R Jenkins, Paul M Sanders, Monia Manieri, Saverio Cinti, Michael J Tisdale, Paul TrayhurnAbstract:Zinc-Alpha2-Glycoprotein (ZAG), a 43-kDa protein, is overexpressed in certain human malignant tumors and acts as a lipid-mobilizing factor to stimulate lipolysis in adipocytes leading to cachexia in mice implanted with ZAG-producing tumors. Because white adipose tissue (WAT) is an endocrine organ secreting a wide range of protein factors, including those involved in lipid metabolism, we have investigated whether ZAG is produced locally by adipocytes. ZAG mRNA was detected by RT-PCR in the mouse WAT depots examined (epididymal, perirenal, s.c., and mammary gland) and in interscapular brown fat. In WAT, ZAG gene expression was evident in mature adipocytes and in stromal-vascular cells. Using a ZAG Ab, ZAG protein was located in WAT by Western blotting and immunohistochemistry. Mice bearing the MAC16-tumor displayed substantial losses of body weight and fat mass, which was accompanied by major increases in ZAG mRNA and protein levels in WAT and brown fat. ZAG mRNA was detected in 3T3-L1 cells, before and after the induction of differentiation, with the level increasing progressively after differentiation with a peak at days 8-10. Both dexamethasone and a beta3 agonist, BRL 37344, increased ZAG mRNA levels in 3T3-L1 adipocytes. ZAG gene expression and protein were also detected in human adipose tissue (visceral and s.c.). It is suggested that ZAG is a new adipose tissue protein factor, which may be involved in the modulation of lipolysis in adipocytes. Overexpression in WAT of tumor-bearing mice suggests a local role for adipocyte-derived ZAG in the substantial reduction of adiposity of cancer cachexia.
Seiji Inoue - One of the best experts on this subject based on the ideXlab platform.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich Alpha2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:Abstract The phospholipase A2(PLA2) inhibitor PLIβ, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527–531). In the present study, the 50-kDa subunit was found to be glycosylated withN-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIβ was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIβ. A cDNA encoding PLIβ was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potentialN-glycosylation sites. The sequence of PLIβ showed no significant homology with that of the known PLA2inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich α2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIβ might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich α2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:The phospholipase A2 (PLA2) inhibitor PLIbeta, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527-531). In the present study, the 50-kDa subunit was found to be glycosylated with N-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIbeta was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIbeta. A cDNA encoding PLIbeta was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potential N-glycosylation sites. The sequence of PLIbeta showed no significant homology with that of the known PLA2 inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich Alpha2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIbeta might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
Naoki Ohkura - One of the best experts on this subject based on the ideXlab platform.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich Alpha2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:Abstract The phospholipase A2(PLA2) inhibitor PLIβ, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527–531). In the present study, the 50-kDa subunit was found to be glycosylated withN-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIβ was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIβ. A cDNA encoding PLIβ was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potentialN-glycosylation sites. The sequence of PLIβ showed no significant homology with that of the known PLA2inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich α2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIβ might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.
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a novel phospholipase a2 inhibitor with leucine rich repeats from the blood plasma of agkistrodon blomhoffii siniticus sequence homologies with human leucine rich α2 Glycoprotein
Journal of Biological Chemistry, 1998Co-Authors: Kohji Okumura, Naoki Ohkura, Seiji Inoue, Kiyoshi Ikeda, Kyozo HayashiAbstract:The phospholipase A2 (PLA2) inhibitor PLIbeta, purified from the blood plasma of Chinese mamushi snake (Agkistrodon blomhoffii siniticus), is a 160-kDa trimer with three 50-kDa subunits; and it inhibits specifically the enzymatic activity of the basic PLA2 from its own venom (Ohkura, N., Okuhara, H., Inoue, S., Ikeda, K., and Hayashi, K. (1997) Biochem. J. 325, 527-531). In the present study, the 50-kDa subunit was found to be glycosylated with N-linked carbohydrate, and enzymatic deglycosylation decreased the molecular mass of the 50-kDa subunit to 39-kDa. One 160-kDa trimer of PLIbeta was found to form a stable complex with three basic PLA2 molecules, indicating that one basic PLA2 molecule would bind stoichiometrically to one subunit of PLIbeta. A cDNA encoding PLIbeta was isolated from a Chinese mamushi liver cDNA library by use of a probe prepared by a polymerase chain reaction on the basis of the partially determined amino acid sequence of the subunit. The cDNA contained an open reading frame encoding a 23-residue signal sequence followed by a 308-residue protein, which contained the sequences of all the peptides derived by lysyl endopeptidase digestion of the subunit. The molecular mass of the mature protein was calculated to be 34,594 Da, and the deduced amino acid sequence contained four potential N-glycosylation sites. The sequence of PLIbeta showed no significant homology with that of the known PLA2 inhibitors. But, interestingly, it exhibited 33% identity with that of human leucine-rich Alpha2-Glycoprotein, a serum protein of unknown function. The most striking feature of the sequence is that it contained nine leucine-rich repeats (LRRs), each of 24 amino acid residues and thus encompassing over two-thirds of the molecule. LRRs in PLIbeta might be responsible for the specific binding to basic PLA2, since LRRs are considered as the motifs involved in protein-protein interactions.