心筋ギャップ結合Cx43のPKC依存性リン酸化による退行変性
詳細
It is well accepted that gap junctions (GJs) play a pivotal role in the intercellular spread of electrical flows between cardiac myocytes. Dysfunction of GJs can thus be one of major arrhythmogenic factors. In this study, we have obtained the evidence that in both type I and II diabetic hearts, myocardial intercellular communication through GJs is impaired via PKC-mediated hyper-phosphorylation of the GJ protein Cx43. Western blot and immunohistochemical analyses of the PKC-activated diabetic hearts indicated that the expression level of Cx43 is significantly reduced compared with control hearts, with altered distribution of sparse or sporadic pattern at the intercalated disk. These alterations were ameliorated by treatment with lysosomal inhibitors as well as PKC inhibitors, but could not be prevented by the proteosmal inhibitor ALLN. These results strongly suggest that facilitated lysosomal degradation of Cx43 via PKC-mediated hyper-phosphorylation may underlie the down-regulation of Cx43 protein in rat diabetic hearts. This mechanism may in part account for the reported vulnerability of rat diabetic hearts to ventricular fibrillation. [J Physiol Sci. 2006;56 Suppl:S73]
