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Gene expression of antioxidant enzymes in experimental diabetic neuropathy
Y Kishi1, K K Nickander, J D Schmelzer
1Department of Neurology, Mayo Clinic and Foundation, Rochester, Minnesota 55905, USA.
Abstract:
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.
Insights
In diabetic neuropathy, antioxidant enzyme gene expression in nerves remains unchanged, even with nerve damage. Enzyme activity may vary with diabetes duration or modifications.
Area of Science:
- Biochemistry
- Neuroscience
- Endocrinology
Background:
- Chronic hyperglycemia in diabetes mellitus impairs nerve blood flow, leading to peripheral sensory neuropathy.
- Oxidative stress and lipid peroxidation are implicated in diabetic neuropathy, with potential reductions in antioxidant defenses.
- Limited data exists on antioxidant enzyme gene expression in long-term experimental diabetic neuropathy.
Purpose of the Study:
- To investigate the gene expression of key antioxidant enzymes (glutathione peroxidase, catalase, superoxide dismutase) in dorsal root and superior cervical ganglia.
- To assess the activity of glutathione peroxidase in the sciatic nerve.
- To evaluate nerve electrophysiology in experimental diabetic neuropathy over 3 and 12 months.
Main Methods:
- Streptozotocin-induced diabetic rat model with 3 and 12 months duration.
- Quantitative gene expression analysis (mRNA) for glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase.
- Enzyme activity assays for glutathione peroxidase in dorsal root ganglion and sciatic nerve.
- Nerve electrophysiological studies (nerve conduction velocity) of caudal, sciatic-tibial, and digital nerves.
Main Results:
- Significant nerve conduction deficits were observed in all tested nerves at both 3 and 12 months of experimental diabetic neuropathy.
- Gene expression levels for glutathione peroxidase, catalase, cuprozinc superoxide dismutase, and manganese superoxide dismutase were not reduced in diabetic neuropathy at either time point.
- Catalase mRNA expression was significantly increased at 12 months in diabetic neuropathy.
- Glutathione peroxidase enzyme activity in the sciatic nerve remained normal.
Conclusions:
- Peripheral nerve tissues in chronic experimental diabetic neuropathy do not exhibit reduced antioxidant enzyme gene expression.
- Observed changes in enzyme activity might be influenced by the duration of diabetes or post-translational modifications rather than gene expression levels.