Methylcobalamin effects on diabetic neuropathy and nerve protein kinase C in rats.
BACKGROUND
Methyl-base-attached cobalamin (Methycobalamin) (MC) has a special affinity for nerve tissues to promote myelination and transport of axonal cytoskeleton. It is not known, however, how MC influences on peripheral nerve in experimental diabetic neuropathy.


METHODS
We studied the effects of MC on expressions and activities of protein kinase C (PKC) in peripheral nerve of streptozotocin-induced diabetic rats. Wistar rats, 8 weeks of age, were rendered diabetic by streptozotocin (40 mg kg(-1), iv) and followed for 16 weeks. A half of diabetic animals were treated with MC (10 mg kg(-1) per every other day, im) after the induction of diabetes. Normal Wistar rats were served as control.


RESULTS
At the end, untreated diabetic animals developed significant delay of nerve conduction velocity (NCV), and MC treatment normalized the NCV. Nerve PKC activity was significantly suppressed in untreated diabetic rats, while the activity was normalized in treated animals. While PKCα located in Schwann cells, PKCβΙα and βII distributed in axoplasm, vascular walls and macrophages. The decreased PKC activity in diabetic nerve was associated with reduced expression of membrane PKCα and increased membrane expression of PKCβII, and MC treatment corrected these changes. Diabetic nerve contained an increased number of macrophages and 8-hydroxydeoxyguanosine-positive cells in the endoneurium, the latter of which was significantly suppressed by MC treatment. Elevated nerve polyol levels in diabetic nerve were partially corrected by MC treatment.


CONCLUSIONS
This study suggested that correction of impaired neural signalling of PKC and oxidative stress-induced damage may be a major attribute to the beneficial effects of MC on diabetic nerve.
Department of Pathology and Molecular Medicine, Hirosaki University Graduate School of Medicine, Hirosaki, Japan.
Hiroki
H
Mizukami
Saori
S
Ogasawara
Shin-Ichiro
S
Yamagishi
Kazunori
K
Takahashi
Soroku
S
Yagihashi
D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D003929:Diabetic Neuropathies / Q000378:metabolism*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009431:Neural Conduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D013223:Statistics as Topic; D014805:Vitamin B 12 / Q000031:analogs & derivatives* / Q000378:metabolism / Q000494:pharmacology
D009419:Nerve Tissue Proteins; C019476:mecobalamin; D011493:Protein Kinase C; D014805:Vitamin B 12