Differential expression of protein kinase C isoforms in streptozotocin-induced diabetic rats

Abstract

Streptozotocin increased blood glucose from 117.0 +/- 3.6 to 510.0 +/- 19.4 mg/dl (N = 8, P < 0.01) and induced albuminuria. PKC isoforms alpha, beta, delta, epsilon, and zeta were all detected in control animals. Western blot showed increased PKC alpha expression in kidney and heart (160% and 170%, respectively). PKC betaI, betaII, and delta expression was not influenced by hyperglycemia. PKC zeta was decreased in diabetic animals in both tissues by 60%. The membrane association of PKC alpha and PKC epsilon was increased; however, the relative amount of PKC in the particulate fraction was not influenced by hyperglycemia. Immunohistochemistry revealed a marked increase in PKC alpha immunoreactivity in renal glomeruli and interstitial capillaries, cardiac capillaries, and skeletal muscle, as well as in the endothelial cells of larger arteries. PKC beta showed a small decrease in the glomeruli. PKC epsilon was increased in renal tubules in diabetic rats but was decreased in the myocardium. PKC zeta was expressed in both myocardial and glomerular cells but was decreased during hyperglycemia. Our results demonstrate that PKC isoforms are differentially regulated in kidney and heart in diabetes. High glucose increases PKC alpha expression, whereas PKC zeta is down-regulated. The finding that PKC alpha is mostly increased in endothelial cells supports a role for PKC alpha in functional endothelial disturbances observed in diabetes.

Angiotensin II Promotes Glucose-Induced Activation of Cardiac Protein Kinase C Isozymes and Phosphorylation of Troponin I

“…Our findings differ somewhat from those reported in whole heart tissue from STZ-induced diabetic rats, in which an increase in the membrane association of one or several of the PKC isozymes ␣, ␤ 2 , ␦, and ⑀ has been reported (13,14,35,36). Differences between our results and those reported in whole heart tissue from STZ diabetic rats may reflect the physiological changes associated with the in vivo diabetic state, such as increased PKC-␣ expression in the nonmyocyte compartment of the myocardium (36). It must also be acknowledged that chronic exposure to a high glucose concentration may result in downregulation in the expression of some, but not all, PKC isozymes.…”

GLUT2 protein at the rat proximal tubule brush border membrane correlates with protein kinase C (PKC)-βl and plasma glucose concentration

“…In keeping with our findings, Hsieh et al reported recently that glucose-induced damage to proximal tubule cells is dependent on PKC-βI [14]. In addition, although there are conflicting results on which isoform(s) is(are) increased in the glomeruli of STZ-diabetic animals, with reports of increased levels of PKC-α [2, 10, 39], -βI [2,39,40], -δ [41] and -ɛ [10,41], PKC-βI seems to be the pathophysiological isoform [40,42]. Indeed, there is strong evidence that diabetes-induced mesangial cell damage occurs as a result of increased glucose uptake by GLUT1, which correlates with increased PKC-βI activation and fibronectin and collagen accumulation [1].…”

“…Studies have also detected altered levels of PKC isoforms in proximal tubular cells following exposure to high glucose concentrations, e.g. PKC-α, -ɛ [10] and -βI [14] specifically were found to be increased. These findings suggest that diabetes-induced alterations in the levels and activity of PKC isoforms may affect proximal tubular cell function, as well as having their already established effects on glomerular cells.…”

“…Immunohistochemistry has localised different isoforms to specific nephron segments, and there are also distinct species differences. In rat kidney, the PKC isoforms α, βI, βII, δ, ɛ and ζ have been detected in the proximal tubule [10] with prominent staining for PKC-α [11,12] and -βI [12] at the BBM. In contrast, PKC-α and-β isoforms are undetectable in mouse proximal tubules, with PKC-ɛ being the predominant isoform in this species [13].…”

Aqueous and Methanolic Extracts of Palm Date Seeds and Fruits (Phoenix dactylifera) Protects against Diabetic Nephropathy in Type II Diabetic Rats

“…In consistence with these findings, previous studies demonstrated significant increase in plasma creatinine and BUN [32][33][34] and serum urea levels [35] in diabetic rats compared to normal. The elevation of serum creatinine, uric acid, urea and UAE are reflection to impairment of kidney functions with development of diabetic nephropathy and loss of glomerular membrane permeability [36].…”