title: Phosphorylation of PRAS40-Thr246 involved in renal lipid accumulation of diabetes.
abstract: Lipid accumulation of kidney is a threat to renal physiological function of diabetes. The previous studies on diabetic nephropathy have demonstrated that activated Akt was involved in renal lipogenesis through enhancing transcription factor SREBP-1. PRAS40 is one of the downstream targets of activated Akt that was reported to involve in lipid metabolism in hepatic cells. However, it is still not clear whether PRAS40 is also involved in the renal lipogenesis of diabetes. Our study revealed that phosphorylation of PRAS40-Thr246 known as inactivated style increased in renal tubular cells of diabetic rats accompanied with over-expression of phospho-Akt, SREBP-1, and ADRP. In addition, in vitro experiment also found that high glucose enhanced expression of phospho-PRAS40-Thr246 followed by increased SREBP-1 and lipid droplets in HKC cells. After treated with LY294002, high glucose-induced HKC cells showed decreased phospho-PRAS40-Thr246, phospho-Akt-Ser473, and SREBP-1. Furthermore, wild type PRAS40 vector-caused increased phospho-PRAS40-Thr246 exaggerated lipid deposits in high glucose-treated HKC cells, which was effectively prevented in cells transfected with mutant PRAS40 vector (T246A). These above data suggested that phosphorylation of PRAS40-Thr246 mediated abnormal lipid metabolism in kidney of diabetes and might be the potential target for treating lipogenesis of diabetic nephropathy.
authors.affiliation: Department of Pathology, Hebei Medical University, Shijiazhuang City, Hebei Province, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Hao
authors.forename: Fan
authors.initials: F
authors.lastname: Li
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.forename: Qingjuan
authors.initials: Q
authors.lastname: Liu
authors.forename: Shuxia
authors.initials: S
authors.lastname: Liu
authors.forename: Hongbo
authors.initials: H
authors.lastname: Li
authors.forename: Huijun
authors.initials: H
authors.lastname: Duan
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D003921:Diabetes Mellitus, Experimental / Q000150:complications* / Q000378:metabolism; D003928:Diabetic Nephropathies; D005786:Gene Expression Regulation / Q000502:physiology; D007328:Insulin / Q000627:therapeutic use; D007668:Kidney / Q000378:metabolism*; D050356:Lipid Metabolism / Q000502:physiology*; D008297:Male; D010766:Phosphorylation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C516104:Akt1s1 protein, rat; D007328:Insulin