Diabetologie und Stoffwechsel 2015; 10 - P89
DOI: 10.1055/s-0035-1549595

The adiponectin paralog CTRP9 but not CTRP7 mediates anti-oxidative effects in adult rat cardiomyocytes through an AMPK, adiponectin receptor and calreticulin dependent mechanism

L Li 1, D Stumpp 1, B Siegler 1, M Micoogullari 1, B Niemann 2, M Aslam 1, H Bugger 3, H Jakoub 1, KD Schlüter 1, RE Silber 4, S Rohrbach 1
  • 1Institute of Physiology, Justus Liebig University Gießen, Gießen, Germany
  • 2Department of Cardiac and Vascular Surgery, Justus Liebig University Gießen, Gießen, Germany
  • 3Cardiology, University Freiburg, Freiburg, Germany
  • 4Department of Cardiothoracic Surgery, University Halle, Halle, Germany

Background: The adipokine adiponectin has direct beneficial effects on cardiomyocytes. However, obesity and ageing are characterized by an adiponectin deficit. Recently, a family of adiponectin paralogs, comprising 15 members so far, was discovered and designated as C1q/tumor necrosis factor-alpha-related proteins (CTRPs). While the protective adiponectin actions are well recognized, questions remain unanswered concerning the role of the CTRPs.

Methods and Results: Among all adiponectin paralogs, CTRP7 and CTRP9 are induced in failing human hearts. CTRP9, which is expressed in adult human cardiomyocytes, protects cardiomyocytes against H2O2-induced cell death. CTRP7, which is mainly derived from cardiac fibroblasts, does not mediate similar protective effects and cannot compensate for a CTRP9 loss. CTRP9 induces an AMPK- and SIRT3-dependent transcriptional activation of Trx1 and SOD2, which results in a reduction of cell death in response to H2O2. AMPK knockdown blunts the CTRP9 effects and results in a strong basal ROS release and increased cell death. Loss of adiponectin receptor 1 (AdipoR1), which was reported to be involved in CTRP-signaling, does not attenuate the CTRP9-induced effects, This is only achieved after knockdown of AdipoR1 and AdipoR2. Knockdown of calreticulin also blunts the CTRP9 effects, suggesting an involvement of this multifunctional protein. Immunoprecipitation shows an interaction of AdipoR1 with AdipoR2 and the co-receptor T-cadherin, but no direct interaction with calreticulin.

Conclusions: These results demonstrate that CTRP9 mediates cardioprotective, antioxidative effects comparable to adiponectin and may thus locally compensate for low circulating adiponectin levels in obesity or ageing.