Upregulation of PKC genes and isozymes in cardiovascular tissues during early stages of experimental diabetes.

The protein kinase C (PKC) pathway has recently been recognized as an important mechanism in the development of diabetic complications including cardiomyopathy and angiopathy. Although an increase in PKC kinase activity has been detected in the cardiovascular system of diabetic patients and animals, it is unclear whether the same pathological condition alters PKC at the transcriptional and translational levels. In this study we assessed quantitatively the mRNA and protein expression profiles of PKC isozymes in the heart and vascular tissues from streptozotocin-induced diabetic pigs. Partial regions of the porcine PKCalpha, beta1, and beta2 mRNAs were sequenced, and real-time RT-PCR assays were developed for PKC mRNA quantification. The results showed a significant increase in the mRNA levels of PKCalpha, beta1, and beta2 in the heart at 4-8 wk of diabetes. In concomitance, the PKCbeta1 and beta2 genes, but not the PKCalpha gene, were upregulated in the diabetic aorta. Correspondingly, there was a significant increase in the protein expression of PKCalpha and beta2 in the heart and PKCbeta2 in the aorta with a time course correlated to that of mRNA expression. In summary, PKCbeta2 was significantly upregulated in the heart and aorta at both the transcriptional and translational levels during early stages of experimental diabetes, suggesting that PKCbeta2 may be a prominent target of diabetic injury in the cardiovascular system.