title: A point mutant of apolipoprotein A-I (V156K) showed enhancement of cellular insulin secretion and potent activity of facultative regeneration in zebrafish.
abstract: 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.
authors.affiliation: School of Biotechnology, Aging-associated Vascular Disease Research Center, Yeungnam University, Gyeongsan, Republic of Korea.
authors.forename: Jeong-Hye
authors.initials: JH
authors.lastname: Yoon
authors.forename: Kyung-Hyun
authors.initials: KH
authors.lastname: Cho
mesh_terms: D019943:Amino Acid Substitution / Q000235:genetics*; D058500:Animal Fins / Q000254:growth & development / Q000502:physiology; D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016632:Apolipoprotein A-I / Q000235:genetics*; D006031:Glycosylation; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D017354:Point Mutation / Q000235:genetics*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism; D012038:Regeneration / Q000502:physiology*; D013997:Time Factors; D015027:Zebrafish / Q000378:metabolism*
chemical_list: D000975:Antioxidants; D016632:Apolipoprotein A-I; D007328:Insulin; D017382:Reactive Oxygen Species