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Polyol pathway and protein kinase C activity of rat Schwannoma cells
Author(s) -
Kamiya Hideki,
Nakamura Jiro,
Hamada Yoji,
Nakashima Eitaro,
Naruse Keiko,
Kato Koichi,
Yasuda Yutaka,
Hotta Nigishi
Publication year - 2002
Publication title -
diabetes/metabolism research and reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.307
H-Index - 110
eISSN - 1520-7560
pISSN - 1520-7552
DOI - 10.1002/dmrr.354
Subject(s) - protein kinase c , polyol pathway , aldose reductase inhibitor , endocrinology , medicine , aldose reductase , chemistry , signal transduction , microbiology and biotechnology , diabetes mellitus , biology , biochemistry
Background Polyol pathway hyperactivity‐induced decreases in protein kinase C (PKC) activities have been proposed as a pathogenic mechanism of diabetic neuropathy. Increased PKC activities have recently been invoked in the pathogenesis of other diabetic complications, especially retinopathy, nephropathy, and macroangiopathy. However, it remains unclear whether PKC activities in neural cells such as Schwann cells are increased, decreased, or unchanged. This study investigated the effects of high glucose and increased polyol pathway activity on neural cell growth and PKC activities. Methods Rat Schwannoma cells were cultured in 5.5 or 20 mM glucose in the presence or absence of an aldose reductase inhibitor, epalrestat (1 µM) for 14 days. Proliferation activities, PKC activities, and the protein expression of PKC isoforms were measured. Results Proliferation and PKC activities under the 20 mM glucose condition were significantly decreased compared to those under the 5.5 mM glucose condition and were prevented by epalrestat. Among PKC isoforms, the protein expression of PKC‐α under the 20 mM glucose condition was significantly reduced compared to that under the 5.5 mM glucose condition. Epalrestat significantly inhibited the decreased expression of PKC‐α protein. There were no significant changes in the protein expression of PKC‐β. Conclusions These results suggest that PKC, especially PKC‐α activity, is decreased in Schwann cells exposed to high glucose and that this deficit is mediated through polyol pathway hyperactivity. Copyright © 2002 John Wiley & Sons, Ltd.