Adiponectin suppresses proliferation and superoxide generation and enhances eNOS activity in endothelial cells treated with oxidized LDL.
Adiponectin (also known as 30-kDa adipocyte complement-related protein or Acrp30) is an abundant adipocyte-derived plasma protein with anti-atherosclerotic and insulin-sensitizing properties. In order to investigate the potential mechanism(s) of the vascular protective effect of adiponectin, we used cultured bovine endothelial cells (BAECs) to study the effect of recombinant globular adiponectin (gAd) on cellular proliferation and the generation of reactive oxygen species (ROS) induced by oxidized LDL (oxLDL). By RT-PCR, we found that BAECs preferentially express AdipoR1, the high-affinity receptor for gAd. Treatment of BAECs with oxLDL (10 microg/ml) for 16h stimulated cell proliferation by approximately 60%, which was inhibited by co-incubation with gAd. Cell treatment with gAd also inhibited basal and oxLDL-induced superoxide release, and suppressed the activation of p42/p44 MAP kinase by oxLDL. The effects of gAd were blocked by a specific polyclonal anti-adiponectin antibody (TJ414). OxLDL-induced BAEC proliferation and superoxide release were inhibited by the NAD(P)H oxidase inhibitor diphenyleneiodonium (DPI), but not the eNOS inhibitor l-nitroarginine methyl ester (l-NAME). Finally, gAd ameliorated the suppression of eNOS activity by oxLDL. These data indicate that gAd inhibits oxLDL-induced cell proliferation and suppresses cellular superoxide generation, possibly through an NAD(P)H oxidase-linked mechanism.
Motoshima
Hiroyuki
H
Dorrance Hamilton Research Laboratories, Division of Endocrinology, Diabetes and Metabolic Diseases, Department of Medicine, Jefferson Medical College of Thomas Jefferson University, Philadelphia, PA 19107, USA.
Wu
Xiangdong
X
Mahadev
Kalyankar
K
Goldstein
Barry J
BJ
D052242:Adiponectin; D000818:Animals; D000838:Anions / Q000737:chemistry; D015153:Blotting, Western; D002374:Catalase / Q000378:metabolism; D002417:Cattle; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000196:embryology / Q000378:metabolism; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D007476:Ionophores / Q000378:metabolism; D008077:Lipoproteins, LDL / Q000378:metabolism*; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D010100:Oxygen / Q000378:metabolism*; D020033:Protein Isoforms; D011506:Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D013481:Superoxides / Q000378:metabolism*; D013997:Time Factors
D052242:Adiponectin; D000838:Anions; D018076:DNA, Complementary; D036341:Intercellular Signaling Peptides and Proteins; D007476:Ionophores; D008077:Lipoproteins, LDL; D020033:Protein Isoforms; D011506:Proteins; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D013481:Superoxides; D004247:DNA; D002374:Catalase; C496314:NOS3 protein, human; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D020928:Mitogen-Activated Protein Kinases; D010100:Oxygen; D019331:NG-Nitroarginine Methyl Ester