Additive effects of hypertension and diabetes on renal cortical expression of PKC-alpha and -epsilon, and alpha-tubulin but not PKC-beta(1) and -beta(2)

Objective This study examined the separate and combined effects of hypertension and diabetes on renal cortical expression of protein kinase C (PKC) isoforms-beta(1), -beta(2), -alpha and -epsilon, to determine whether albuminuria is the result of an increase in the expression of one or a combination of PKC isoforms. Corresponding changes in renal microtubules were also assessed. Methods Diabetes (D) was induced in Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR) by streptozotocin. After 24 weeks, PKC expression was determined by Western blot and microtubules were assessed by immunohistochemistry for alpha-tubulin protein. Results Diabetes was characterized by significant increases in glycated haemoglobin (HbA(1c)) as compared to controls (C). There was a significant increase of three- to four-fold in PKC protein content for all four isoforms in renal cortex from SHR-C and WKY-D, and similar and significant levels of albuminuria (similar to 10 mg/24 h) observed in these groups in comparison to WKY-C (similar to 1 mg/24 h). Interestingly, PKC-alpha and -epsilon but not PKC-beta(1) and -beta(2) protein content was doubled in SHR-D, and albuminuria increased tenfold (similar to 100 mg/24 h) in comparison to SHR-C and WKY-D. These changes were paralleled by a significant decrease in alpha-tubulin protein content of similar to 50% in SHR-C and similar to 33% in WKY-D compared to WKY-C, with a further decrease of similar to 67% in SHR-D compared to WKY-C. Conclusion These findings indicate that PKC expression can be increased by either diabetes or hypertension, and that there are further specific increases in the expression of PKC isoforms -alpha and -epsilon in the model of combined diabetes and hypertension. In addition, the degree of disruption in microtubular cytoskeleton appears to be correlated with PKC activation and levels of albuminuria. (c) 2003 Lippincott Williams C Wilkins.