Stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced NO production: vasorelaxation in response to globular adiponectin.
The present study examined potential interactions between endothelial NO synthase (eNOS), heat shock protein (HSP)90, and Akt in vascular endothelial cells stimulated with globular adiponectin to produce nitric oxide (NO). Globular adiponectin-induced eNOS phosphorylation was accompanied by eNOS-HSP90-Akt complex formation, resulting in a dose-dependent increase in NO release. Globular adiponectin stimulated binding of HSP90 to eNOS, and inhibition of HSP90 significantly suppressed globular adiponectin-stimulated NO release. Globular adiponectin also caused Akt phosphorylation, and inhibition of PI3 kinase significantly suppressed globular adiponectin-stimulated NO release. This study also examined whether globular adiponectin really induces endothelial-dependent vasodilation using rings from rat thoracic aorta. It was observed that globular adiponectin caused dose-dependent vasorelaxation in the aorta. These results indicate that stimulated HSP90 binding to eNOS and activation of the PI3-Akt pathway contribute to globular adiponectin-induced eNOS phosphorylation and NO production, and to endothelium-dependent vasorelaxation.
Xi
Wang
W
Department of Endocrinology and Metabolism, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
Satoh
Hiroko
H
Kase
Hiroyuki
H
Suzuki
Kunihiro
K
Hattori
Yoshiyuki
Y
D052242:Adiponectin; D000818:Animals; D002417:Cattle; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D042783:Endothelial Cells / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
D052242:Adiponectin; D018841:HSP90 Heat-Shock Proteins; D036341:Intercellular Signaling Peptides and Proteins; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt