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Aldose reductase inhibition increases CNTF-like bioactivity and protein in sciatic nerves from galactose-fed and normal rats
- Source :
- Diabetes. 46(4)
- Publication Year :
- 1997
-
Abstract
- The impact of exaggerated polyol pathway flux on ciliary neurotrophic factor (CNTF)-like bioactivity and expression of CNTF in rat sciatic nerve was examined after 2 months of galactose intoxication. Polyol content was elevated (P < 0.001) and motor nerve conduction velocity reduced (P < 0.05) in galactose-fed rats compared with control animals or control and galactose-fed rats treated with the aldose reductase inhibitor (ARI) Ponalrestat. CNTF-like bioactivity in the galactose-fed group was reduced to 30% of that assayed in the control group (P < 0.001). ARI treatment significantly increased CNTF-like bioactivity by 60% compared with the untreated galactose group (P < 0.05) but did not restore it to control levels. Unexpectedly, bioactivity in ARI-treated control animals was increased by nearly 250% compared with untreated controls (P < 0.005). In addition to the deficit in CNTF bioactivity in untreated galactose rats, the expression of protein, but not of mRNA, was reduced (P < 0.05). In ARI-treated control and galactose-fed rats, the expression of CNTF peptide was significantly enhanced above control levels (both P < 0.05). Concomitant with the reduction in CNTF levels, there was a shift in the axonal size-frequency distribution of myelinated fibers toward smaller axons in galactose-fed rats that was prevented by ARI treatment. Since galactose feeding has little impact on levels of CNTF mRNA, these observations suggest that deficits in CNTF-like bioactivity may result from a posttranscriptional modification of neurotrophic protein expression or turnover. Unlike other functional and structural disorders in galactose neuropathy, factors other than polyol accumulation may contribute to the deficit in CNTF-like bioactivity.
- Subjects :
- medicine.medical_specialty
Endocrinology, Diabetes and Metabolism
Enzyme-Linked Immunosorbent Assay
Nerve Tissue Proteins
Ciliary neurotrophic factor
Rats, Sprague-Dawley
chemistry.chemical_compound
Polyol pathway
Aldehyde Reductase
Internal medicine
Gene expression
Internal Medicine
medicine
Animals
Ciliary Neurotrophic Factor
Nerve Growth Factors
RNA, Messenger
Enzyme Inhibitors
Aldose reductase
biology
Galactose
Blotting, Northern
Aldose reductase inhibitor
Sciatic Nerve
Rats
Endocrinology
chemistry
biology.protein
Phthalazines
Biological Assay
Female
Sciatic nerve
medicine.drug
Neurotrophin
Subjects
Details
- ISSN :
- 00121797
- Volume :
- 46
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- Diabetes
- Accession number :
- edsair.doi.dedup.....2dacd35ce7b65ef34c7983ef51f24484