Mahali, S.K. and Verma, N. and Manna, S.K. (2014) Advanced Glycation End Products Induce Lipogenesis: Regulation by Natural Xanthone through Inhibition of ERK and NF-kappa B. Journal of Cellular Physiology, 229 (12). pp. 1972-1980. ISSN 1097-4652

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Abstract

Advanced glycation end products (AGE) accumulate in diabetic patients and aged persons due to high amounts of 3- or 4-carbon derivatives of glucose. Understanding the mechanism of AGE-mediated signaling leading to these consequences, like oxidative stress, inflammation, apoptosis, etc. and its regulation would be a viable strategy to control diabetic complication and age-related diseases. We have detected the probable mechanism by which AGE increases lipogenesis, the cause of fatty liver in diabetic patients. AGE increased lipid accumulation in different cells as shown by Oil Red O staining. AGE-mediated regulation of several transcription factors was determined by gel shift assay. Antioxidants like NAC, PDTC, and vitamin C, except mangiferin, were unable to protect AGE-induced activation of SREBP and subsequent lipid accumulation. AGE increased the phosphorylation of ERK, and IKK and also DNA binding ability of SREBP, thereby its dependent gene transcription. AGE induces NF-B which might suppress PPAR activity, in turn reducing lipid breakdown and mobilization. Mangiferin not only inhibits AGE-mediated ROI generation that requires NF-B activation, but also inhibits ERK and IKK activity, thereby suppression of SREBP activity and lipogenesis. Mangiferin has shown a double-edged sword effect to suppress AGE-mediated ailments by reducing ROI-mediated responses as antioxidant and inhibiting SREBP activation thereby lipogenesis, suggesting its potential efficacy against diabetes and obesity-related diseases. J. Cell. Physiol. 229: 1972-1980, 2014. (c) 2014 Wiley Periodicals, Inc.

Item Type:	Article
Uncontrolled Keywords:	Antioxidants NF-kappa B PPAR gamma
Subjects:	Molecular Biology
Depositing User:	Unnamed user with email alok@urdip.res.in
Date Deposited:	31 Mar 2015 07:01
Last Modified:	18 May 2015 17:56
URI:	http://cdfd.sciencecentral.in/id/eprint/7

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