title: Globular adiponectin activates nuclear factor-kappaB and activating protein-1 and enhances angiotensin II-induced proliferation in cardiac fibroblasts.
abstract: Adiponectin is present in the serum as a trimer, hexamer, or high-molecular weight form. A proteolytic cleavage product of adiponectin, known as globular adiponectin (gAd), also circulates in human plasma. The biological activities of these isoforms are not well characterized. Pressure overload in adiponectin-deficient mice results in enhanced concentric cardiac hypertrophy and increased mortality, suggesting that adiponectin inhibits hypertrophic signaling in the myocardium. Therefore, we examined whether gAd exerts the same effects on myocardium signaling. Nuclear factor-kappaB (NF-kappaB) and activating protein-1 (AP-1) activation were examined using cardiac fibroblasts prepared from the ventricles of 1- to 2-day-old Wistar rats and grown in culture. gAd activated NF-kappaB and enhanced tumor necrosis factor-alpha (TNF-alpha)-induced NF-kappaB activity. gAd also activated AP-1 and enhanced angiotensin II (Ang II)-induced AP-1 activity. gAd induced mRNA expression of c-fos and c-jun and activated extracellular signal-regulated kinase. Thus, gAd enhanced Ang II-induced DNA and collagen synthesis. Antibodies against adiponectin receptor (AdipoR)1 and AdipoR2 elicit activation of NF-kappaB or AP-1, two redox-sensitive transcription factors. Thus, rather than having an antihypertrophic effect, gAd might contribute to the activation of myocardium signaling, leading to myocardial hypertrophy.
authors.affiliation: Department of Endocrinology and Metabolism, Dokkyo Medical University School of Medicine, Mibu, Tochigi 321-0293, Japan. yhattori@dokkyomed.ac.jp
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Hattori
authors.forename: Sachiko
authors.initials: S
authors.lastname: Hattori
authors.forename: Kazumi
authors.initials: K
authors.lastname: Akimoto
authors.forename: Toshio
authors.initials: T
authors.lastname: Nishikimi
authors.forename: Kunihiro
authors.initials: K
authors.lastname: Suzuki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Matsuoka
authors.forename: Kikuo
authors.initials: K
authors.lastname: Kasai
mesh_terms: D052242:Adiponectin / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D000906:Antibodies; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation; D016762:Genes, fos / Q000502:physiology; D016758:Genes, jun / Q000502:physiology; D009206:Myocardium / Q000166:cytology*; D016328:NF-kappa B / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D018808:Transcription Factor AP-1 / Q000378:metabolism*
chemical_list: D052242:Adiponectin; C499920:Adipoq protein, rat; D000906:Antibodies; D016328:NF-kappa B; D012333:RNA, Messenger; D054419:Receptors, Adiponectin; D011956:Receptors, Cell Surface; D018808:Transcription Factor AP-1; C504339:adiponectin receptor 1, rat; C506573:adiponectin receptor 2, rat; D000804:Angiotensin II; D048049:Extracellular Signal-Regulated MAP Kinases