Cilostazol prevents impairment of slow axonal transport in streptozotocin-diabetic rats.
We studied the effects of cilostazol, an antiplatelet and vasodilating agent, on axonal transport patterns of cytoskeletal proteins in the motor fibers of sciatic nerve of streptozotocin-induced diabetic rats. Proteins labeled with L-[35S]methionine in 6-mm consecutive segments of the nerve were analyzed electrophoretically following fractionation into Triton-soluble and-insoluble subpopulations. Transport rates of proteins (particularly neurofilaments) in slow component a were reduced by 50% 2 weeks after labeling (4 weeks after streptozotocin). An apparent reduction of tubulin and actin was observed at later intervals after induction of diabetes. Actin transported in slow component b was also impaired, though to a lesser extent than in component a. Cilostazol prevented transport impairment of both slow components a and b without affecting hyperglycemia or reduction in body weight gain. These results suggest that in sciatic motor fibers early defects in slowly transported proteins are more marked in slow component a, and that impairment may be caused primarily by hemodynamic abnormalities.
Yamamoto
Y
Y
First Institute of New Drug Research, Otsuka Pharmaceutical Co., Ltd., Tokushima, Japan. y_yamamoto@tky.otsuka.co.jp
Yasuda
Y
Y
Komiya
Y
Y
D000818:Animals; D001370:Axonal Transport / Q000187:drug effects*; D001786:Blood Glucose / Q000378:metabolism; D001835:Body Weight / Q000187:drug effects; D000077407:Cilostazol; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000378:metabolism; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013777:Tetrazoles / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology*
D001786:Blood Glucose; D003598:Cytoskeletal Proteins; D010975:Platelet Aggregation Inhibitors; D013777:Tetrazoles; D014665:Vasodilator Agents; D008715:Methionine; D000077407:Cilostazol