A Point Mutant of Apolipoprotein A-I (V156K) Showed Enhancement of Cellular Insulin Secretion and Potent Activity of Facultative Regeneration in Zebrafish
| Autor: | Jeong-Hye Yoon, Kyung-Hyun Cho |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
Aging
medicine.medical_specialty Glycosylation Time Factors Antioxidant Apolipoprotein B medicine.medical_treatment Stimulation Antioxidants Fin regeneration chemistry.chemical_compound Glycation Insulin-Secreting Cells Internal medicine Insulin Secretion medicine Animals Insulin Point Mutation Regeneration Fragmentation (cell biology) Zebrafish Apolipoprotein A-I biology Regeneration (biology) Fructose Rats Endocrinology Amino Acid Substitution chemistry Animal Fins biology.protein Geriatrics and Gerontology Reactive Oxygen Species |
| Zdroj: | Rejuvenation Research. 15:313-321 |
| ISSN: | 1557-8577 1549-1684 |
| DOI: | 10.1089/rej.2011.1246 |
| Popis: | Sensitivity of glycation and functional changes were compared between wild-type (WT) and the V156K mutant of apolipoprotein A-I in the reconstituted high-density lipoproteins (rHDL) state. WT-rHDL showed increased production of advanced glycated end (AGE) products with proteolytic fragmentation by fructose treatment (final 5 mM) for 48 hr; however, V156K-rHDL was more resistant to the same fructosylation and protein cleavage. Glycated WT-rHDL severely lost antioxidant activity; in contrast, V156K-rHDL showed much less AGE production and retained stronger antioxidant properties in the glycated state. In both native and glycated states, V156K-rHDL showed significantly enhanced stimulation activity for insulin secretion from the rat pancreatic β-cell, whereas WT-rHDL induced less insulin secretion by glycation. In the zebrafish model, under diabetic and hyperlipidemic diet conditions, injection of native V156K-rHDL caused an approximate five-fold increase in fin regeneration activity compared to native WT-rHDL over 120 hr. Under the same conditions, injection of glycated WT-rHDL caused severe tissue damage in tail fins after 48 hr, whereas glycated V156K-rHDL showed normal regeneration. In conclusion, insulin secretion and tissue rejuvenation activities of WT-rHDL were nearly depleted by fructosylation, but V156K-rHDL did not lose its beneficial activity. These results suggest that V156K-rHDL can be applied to facilitate facultative regeneration in aging-related complications. |
| Databáze: | OpenAIRE |
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