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Hypomethylation of mitochondrial D-loop and ND6 with increased mitochondrial DNA copy number in the arsenic-exposed population

Author:
Sanyal, Tamalika, Bhattacharjee, Pritha, Bhattacharjee, Sandip, Bhattacharjee, Pritha
Source:
Toxicology 2018 v.408 pp. 54-61
ISSN:
0300-483X
Subject:
adverse effects, arsenic, case-control studies, electron transport chain, epigenetics, gene expression, genes, groundwater, groundwater contamination, human health, membrane potential, methylation, mitochondria, mitochondrial DNA, oxidative stress, quantitative polymerase chain reaction, reactive oxygen species, skin lesions, India
Abstract:
Groundwater arsenic contamination has become a serious global concern due to its adverse effects on human health. Arsenic-induced reactive oxygen species trigger oxidative stress inside mitochondria, which initiate a cascade of events including altered mitochondrial (mt) membrane potential, uncoupling of electron transport chain, and mtDNA damage. A case-control study was conducted to examine the association between arsenic exposure and differences in mtDNA methylation and to assess the downstream consequences. We recruited 221 arsenic-exposed individuals, including 106 individuals with skin lesions (WSL) and 115 subjects without any skin lesions (WOSL) from the Murshidabad district, West Bengal, India. The unexposed group included 101 individuals from the arsenic unexposed area in East Midnapore. We analyzed the status of mtDNA methylation in D-loop region and ND6 gene by methylation-specific PCR. Gene expression was studied by quantitative real-time PCR. Significant hypomethylation in both D-loop and ND6 was observed with a consequent increase in their target gene expression and higher mtDNA copy number in arsenic-exposed populations compared to controls. Further mechanistic insights regarding mitochondrial epigenetic alteration in arsenic exposure will be of critical importance for the prevention of adverse health effects.
Agid:
6144666