Pro-apoptotic effects of anti-β1-adrenergic receptor antibodies in cultured rat cardiomyocytes: Actions on endoplasmic reticulum and the prosurvival PI3K-Akt pathway

• Published in: Autoimmunity (Chur, Switzerland) Switzerland), 2008, Vol.41 (6), p.434-441
• Main Authors: Liang, Chang-Seng, Mao, Weike, Liu, Jiahao
• Format: Article
• Language: English
• Subjects: caspase-12, Akt; Myocyte apoptosis; p38 MAP kinase
• ISSN: 0891-6934; 1607-842X
• DOI: 10.1080/08916930802031710

An anti-β1-adrenergic receptor antibody against the second extracellular receptor loop (β1-ECII) has been shown to cause myocyte apoptosis and dilated cardiomyopathy in animals. We report in this review that the anti-β1-ECII antibody increases intracellular Ca++ transients and exerts a direct apoptotic effect in cultured neonatal rat cardiomyocytes. Both Fab and Fc fragments are required for the full expression of the apoptotic effects of the anti-β1-ECII antibody. Our studies further suggest that the anti-β1-ECII-antibody acts primarily on the cardiac β1-adrenergic receptor and its post-receptor activation of Ca++/Calmodulin dependent protein kinase II (CaMKII) and p-38 mitogen-activated protein kinase (MAPK), leading to endoplasmic reticulum stress as evidenced by the increased expressions of GRP78 and CHOP, as well as the increased processing of the initiator procaspase-12. Also, observed with the apoptotic effect of anti-β1-ECII antibody is reduced activity of the phosphatidylinositol (PI) 3-kinase/Akt/STAT3 signaling pathway. Our results suggest that agents that block the activation of p38-MAPK/endoplasmic reticulum stress or reverse the suppression of the prosurvival PI3K/Akt/STAT3 pathway may be explored as potential novel therapeutic modalities in the treatment of dilated cardiomyopathy.