TAILIEUCHUNG - Báo cáo khoa học: SREBPs: physiology and pathophysiology of the SREBP family

Sterol regulatory element-binding proteins (SREBPs) have been established as physiological regulators of lipid synthesis. The molecular mechanisms by which cellular sterol balance and nutritional states regulate SREBP acti-vities are the current research focus of this field. | MINIREVIEW SREBPs physiology and pathophysiology of the SREBP family Hitoshi Shimano Department of InternalMedicine Endocrinoglogy and Metabolism Graduate Schoolof Comprehensive Human Sciences University of Tsukuba Japan Keywords cholesterol diabetes dyslipidemia fatty acids fatty liver insulin resistance lipotoxicity metabolic syndrome SREBP trigylcerides Correspondence H. Shimano Department of Internal Medicine Endocrinoglogy and Metabolism Graduate School of Comprehensive Human Sciences University of Tsukuba 1-1-1 Tennodai Tsukuba 305-8575 Japan Fax 81 29 853 3174 Tel 81 29 853 3053 E-mail shimano-tky@ hshimano@ Received 2 August 2008 revised 11 November 2008 accepted 18 November 2008 doi Sterol regulatory element-binding proteins SREBPs have been established as physiological regulators of lipid synthesis. The molecular mechanisms by which cellular sterol balance and nutritional states regulate SREBP activities are the current research focus of this field. Meanwhile it has been shown that overnutrition or disturbed energy balance causes accumulation of tissue lipids leading to metabolic disorders often referred to as lipotox-icity . In this overview I discuss the pathological aspects of SREBPs which contribute to lipotoxicity in a wide variety of organs including hepatic insulin resistance in hepatosteatosis impaired insulin secretion in pancreatic b-cells diabetic nephropathy cardiac arrythmiasis and obesity. SREBP-2 and sterol regulation The sterol regulatory element-binding protein SREBP family originally identified as basic helix-loop-helix bHLH leucine zipper transcription factors by Goldstein and Brown is involved in the regulation of genes participating in cholesterol biosynthesis and low-density lipoprotein receptor synthesis 1 2 . They are now established as global regulators of lipid synthesis. What makes this bHLH family unique is that SREBPs are synthesized and located on the endoplasmic .

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