Journal article
N. Tyagi, N. Narayanan, P. Mishra, Natia Qipshidze, S. Givvimani, Suresh Tyagi
2012
2012
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APA
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Tyagi, N., Narayanan, N., Mishra, P., Qipshidze, N., Givvimani, S., & Tyagi, S. (2012). Epigenetic Reprogramming of Mitochondrial Dysfunction in hyperhomocysteinemia.
Chicago/Turabian
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Tyagi, N., N. Narayanan, P. Mishra, Natia Qipshidze, S. Givvimani, and Suresh Tyagi. “Epigenetic Reprogramming of Mitochondrial Dysfunction in Hyperhomocysteinemia” (2012).
MLA
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Tyagi, N., et al. Epigenetic Reprogramming of Mitochondrial Dysfunction in Hyperhomocysteinemia. 2012.
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@article{n2012a,
title = {Epigenetic Reprogramming of Mitochondrial Dysfunction in hyperhomocysteinemia},
year = {2012},
author = {Tyagi, N. and Narayanan, N. and Mishra, P. and Qipshidze, Natia and Givvimani, S. and Tyagi, Suresh}
}
Abstract
An elevated level of homocysteine (Hyperhomocysteinemia) is associated with increased risk factor of neurological disorder. Homocysteine (Hcy) modulates cellular methylation reactions. Previously we have demonstrated that HHcy caused significant metabolic changes and altered mitochondrial function in mouse brain endothelial cells (bEND3). However, the mechanisms behind such alterations remain unclear. The present study examined if the effects of Hcy on mitochondria dysfunction are mediated through an epigenetic mechanism. Following exposure to Hcy for 72 h, global DNA methylation and histone H3 lysine 9 (H3K9) acetylation were examined using flow cytometric analysis. Total DNA methyltransferase activity (DNMT) and protein levels of DNMT 3 were measured. Mitochondrial respiratory capacity and mitochondrial permeability transition (MPT) were measured by fluorescence dye. The result suggested that HHcy caused global DNA hypomethylation and histone hyperacetylation. Total DNMT activity significantly decreased which was accompanied by a significant reduction in protein levels of DNMT 3 and loss of MPT. Treatment of bEND3 with the DNMT inhibitor, 5‐aza‐2′‐deoxycytidine, mimicked the functional changes induced by Hcy. This study suggests that the Hcy related metabolic changes including altered mitochondrial function may be mediated through an epigenetic mechanism.
