Impaired reductive regeneration of ascorbic acid in the Goto–Kakizaki diabetic rat
| Autor: | Masayasu Inoue, Misato Kashiba, Jun Oka, Takayo Inayama, Morimitsu Nishikimi, Takahiro Ishikawa, Haruaki Kageyama, Asako Kageyama, Rumi Ichikawa, Shuji Inoue |
|---|---|
| Rok vydání: | 2000 |
| Předmět: |
chemistry.chemical_classification
medicine.medical_specialty Antioxidant medicine.medical_treatment Cell Biology medicine.disease Ascorbic acid medicine.disease_cause Biochemistry Cytosol chemistry.chemical_compound Enzyme Endocrinology chemistry Diabetes mellitus Internal medicine medicine Dehydroascorbic acid Northern blot Molecular Biology Oxidative stress |
| Zdroj: | Biochemical Journal. 351:313-318 |
| ISSN: | 1470-8728 0264-6021 |
| Popis: | Ascorbic acid (AA) is a naturally occurring major antioxidant that is essential for the scavenging of toxic free radicals in both plasma and tissues. AA levels in plasma and tissues have been reported to be significantly lower than normal in diabetic animals and humans, and might contribute to the complications found at the late stages of diabetes. In this study, plasma and hepatic AA levels and AA regeneration were studied in the Goto–Kakizaki diabetic rat (GK rat) to elucidate the mechanism of decreasing plasma and hepatic AA levels in diabetes. AA concentrations in the plasma and liver were significantly lower in GK than in control rats. AA levels in primary cultured hepatocytes derived from GK rats were lower than those derived from control Wistar rats with or without dehydroascorbic acid (DHA) in the medium. Among various enzyme activities that reduce DHA to AA, the NADPH-dependent regeneration of AA in the liver was significantly suppressed in GK rats. Northern blot analysis revealed that only the expression of 3-α-hydroxysteroid dehydrogenase (AKR) was significantly suppressed in these rats. These results suggest that decreased AA-regenerating activity, probably through decreased expression of AKR, contributes to the decreased AA levels and increased oxidative stress in GK rats. |
| Databáze: | OpenAIRE |
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