Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E.

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Ganz MB, Seftel A

Glucose-induced changes in protein kinase C and nitric oxide are prevented by vitamin E.

Am J Physiol Endocrinol Metab. 2000 Jan;278(1):E146-52.

PubMed ID

10644549 [ View in PubMed

]

Abstract

Changes in activity or expression of protein kinase C (PKC), reactive oxygen products, and nitric oxide (NO) may account for the alteration in cell behavior seen in diabetes. These changes have been proposed to be part of the pathophysiology of erectile dysfunction. We sought to ascertain if corpus cavernosal vascular smooth muscle cells (CCSMC) grown in a high glucose milieu exhibit changes in the activity and expression of PKC isoforms, NO, and reactive oxygen products and to find out if these changes are prevented by alpha-tocopherol. Rat CCSMC were grown in 5, 15, and 30 mM glucose concentrations for 3, 7, and 14 days. PKC isoform expression was assayed with isoform-specific antibodies. In CCSMCs grown in 30 mM glucose for 2-wk, PKC-beta(2)-isoform was upregulated (n = 4; P < 0.01), whereas the expression of alpha-, delta-, epsilon-, and beta(1)-isoforms was unchanged. NO as measured by nitrate-to-nitrite ratio was greatly diminished at 14 days in 30 mM (n = 4; P < 0.002) compared with 5 mM glucose. Reactive oxygen products were upregulated at 14 days when they were assayed by the fluorescent probe dichlorofluorescein diacetate bis(acetoxy-methyl) (DCFH-DA) (n = 5; P < 0.01). When these same cells were exposed to alpha-tocopherol for 14 days, there was a reduction of PKC-beta(2) (57.8%; P < 0.01; n = 4) and a reduction in reactive oxygen product formation (71.1%; P < 0.001; n = 4), along with an increase in nitrate-to-nitrite ratio (43.9%; P < 0.01, n = 4). These results suggest that there may be an interrelationship between PKC, NO, and reactive oxygen product formation in CCSMC exposed to a high glucose environment.

DrugBank Data that Cites this Article

Drug Targets

Drug	Target	Kind	Organism	Pharmacological Action	Actions
alpha-Tocopherol succinate	Protein kinase C beta type	Protein	Humans	Unknown	Not Available	Details
D-alpha-Tocopherol acetate	Protein kinase C beta type	Protein	Humans	Unknown	Not Available	Details
Vitamin E	Protein kinase C beta type	Protein	Humans	Unknown	Not Available	Details