A Point Mutant of Apolipoprotein A-I (V156K) Showed Enhancement of Cellular Insulin Secretion and Potent Activity of Facultative Regeneration in Zebrafish

作者：Yoon Jeong Hye; Cho Kyung Hyun^*

来源：Rejuvenation Research, 2012, 15(3): 313-321.

DOI：10.1089/rej.2011.1246

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 5mM) 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 beta-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.

• 出版日期2012-6