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Differential influence of increased polyol pathway on protein kinase C expressions between endoneurial and epineurial tissues in diabetic mice
Author(s) -
Yamagishi ShinIchiro,
Uehara Kenji,
Otsuki Saori,
Yagihashi Soroku
Publication year - 2003
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.2003.02011.x
Subject(s) - polyol pathway , endoneurium , protein kinase c , aldose reductase , endocrinology , medicine , epineurium , aldose reductase inhibitor , diabetes mellitus , streptozotocin , diabetic neuropathy , chemistry , kinase , biochemistry , sciatic nerve
To explore the relationship between polyol pathway and protein kinase C (PKC), we examined PKC activities and expressions of PKC isoforms separately in endoneurial and vessel‐rich epineurial tissues in diabetic mice transgenic for human aldose reductase (Tg). Tg and littermate control mice (Lm) were made diabetic by streptozotocin at 8 weeks of age and treated orally with aldose reductase inhibitor (ARI) (fidarestat 3–5 mg/kg/day) or placebo for 12 weeks. At the end, compared with non‐diabetic state, sorbitol contents were increased 6.4‐fold in endoneurium and 5.1‐fold in epineurium in diabetic Tg, whereas the increase was detected only in endoneurium in diabetic Lm. Endoneurial PKC activity was significantly reduced in diabetic Tg. By contrast, epineurial PKC activity was increased in both diabetic Lm and diabetic Tg and there was no significant difference between the two groups. These changes were all corrected by ARI treatment. Consistent with the changes of PKC activities, diabetic Tg showed decreased expression of PKCα in endoneurium, whereas there was an increased expression of PKCβII in epineurium in both diabetic Tg and diabetic Lm. These findings suggest the presence of dichotomous metabolic pathway between neural and vascular tissues in the polyol‐PKC‐related pathogenesis of diabetic neuropathy.