Protein Kinase C Isoform Expression in Normal and Failing Rabbit Hearts
作者:Patricia Rouet‐Benzineb, Kamiar Mohammadi, J. Perennec, Madeleine Poyard, Nour El Houda Bouanani, Bertrand Crozatier · 发表于:Circulation Research · 年份:1996 · DOI:10.1161/01.res.79.2.153 · 被引用次数:72 · 研究领域:Protein Kinase Regulation and GTPase Signaling、Signaling Pathways in Disease、Cell death mechanisms and regulation
Protein kinase C (PKC) is activated by alpha-adrenergic stimulation. Molecular analysis showed that PKC consists of a family of at least 12 isozymes. Studies of their distribution in the heart showed conflicting results. The first goal of our study was thus to characterize cardiac PKC in normal rabbits. PKC plays an important role in gene expression, cell growth, and differentiation and is involved in the hypertrophy phase of cardiac overload, but since its expression has never been evaluated in heart failure, the second goal of our study was to evaluate PKC activity and isoform expression in rabbits with heart failure induced by a double hemodynamic overload (aortic insufficiency followed by an aortic stenosis). In the first part of the study, PKC isoform expression analyzed in normal rabbits by immunoblotting showed that isoforms alpha, beta, epsilon, and zeta were expressed along with PKC gamma, which had never been detected in the heart. PKC gamma expression was also identified by polymerase chain reaction, and immunofluorescence techniques showed a localization on intercalated disks associated with the membrane localization observed with the other isoforms. In the second part of the study, PKC activity, content, and isoform expression showed a decrease of 37% in the failing group. PKC immunodetection with a monoclonal antibody (Mab 1.9) recognizing the catalytic domain of all PKC isoforms revealed a 20% decrease in the failing ventricles compared with normal left ventric...