Gene expression of antioxidant enzymes in experimental diabetic neuropathy.
Chronic hyperglycemia results in a large deficit in nerve blood flow. Both autoxidative- and ischemia-induced lipid peroxidation occurs, with resultant peripheral sensory neuropathy in streptozotocin-induced diabetes in the rat. Free radical defenses, especially involving antioxidant enzymes, have been suggested to be reduced, but scant information is available on chronic hyperglycemia. We evaluated the gene expression of glutathione peroxidase, catalase, and superoxide dismutase (cuprozinc and manganese separately) in L4,5 dorsal root ganglion (DRG) and superior cervical ganglion, as well as enzyme activity of glutathione peroxidase in DRG and sciatic nerve in experimental diabetic neuropathy of 3 months and 12 months durations. We also evaluated nerve electrophysiology of caudal, sciatic-tibial, and digital nerves. A nerve conduction deficit was seen in all nerves in experimental diabetic neuropathy at both 3 and 12 months. Gene expression of glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in experimental diabetic neuropathy at either 3 or 12 months. Catalase mRNA was significantly increased in experimental diabetic neuropathy at 12 months. Glutathione peroxidase enzyme activity was normal in sciatic nerve. We conclude that gene expression is not reduced in peripheral nerve tissues in very chronic experimental diabetic neuropathy. Changes in enzyme activity may be related to duration of diabetes or due to post-translational modifications.
Kishi
Y
Y
Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Nickander
K K
KK
Schmelzer
J D
JD
Low
P A
PA
D000818:Animals; D001786:Blood Glucose; D015152:Blotting, Northern; D001835:Body Weight; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D003001:Cloning, Molecular; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000235:genetics; D003929:Diabetic Neuropathies / Q000201:enzymology* / Q000235:genetics; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000201:enzymology; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D006442:Glycated Hemoglobin / Q000032:analysis; D008297:Male; D009431:Neural Conduction / Q000502:physiology; D018384:Oxidative Stress / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000201:enzymology; D017783:Superior Cervical Ganglion / Q000201:enzymology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism
D001786:Blood Glucose; D002374:Catalase; D005979:Glutathione Peroxidase; D006442:Glycated Hemoglobin; D012333:RNA, Messenger; D013482:Superoxide Dismutase