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Tissue Homocysteine Levels are Negatively Correlated with Mitochondrial ETC Complex I Gene Expression in Mice
Author(s) -
Cueto Ramon,
Shan Huimin,
Yang Xiaofeng,
Wang Hong
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.884.65
Subject(s) - gene , hyperhomocysteinemia , biology , gene expression , homocysteine , microbiology and biotechnology , genetics , biochemistry
Hyperhomocysteinemia (HHcy) is an independent risk factor for cardiovascular disease (CVD). It has been suggested that HHcy may cause mitochondrial (Mt) damage which leads to increased oxidative stress resulting in CVD. However, the mechanism of how HHcy damages Mt remains to be elucidated. Our goal is to identify HHcy‐responsive genes in Mt electron transport chain (ETC). We established tissue expression profile of 97 Mt ETC genes in 20 human and 19 mouse tissues using the NCBI UniGene profile database by database mining. We measured homocysteine (Hcy) metabolite (Hcy, SAH and SAM) concentrations in 6 tissues (heart, liver, lung, kidney, spleen and brain) from C57BL/6J mice by mass spectrometry. We employed correlation analysis to identify the relationship of Hcy metabolite tissue concentrations with Mt ETC gene expression levels. We screened Hcy‐responsive genes using NCBI GEO profile database to consolidate the correlation between Hcy tissue concentrations and Mt ETC gene expression levels. We identified 15 Mt ETC genes which expression were negatively correlated with Hcy tissue levels, as the Hcy‐responsive genes, including 12 Mt Com I genes, 1 Com IV and 2 Com V genes. We established tissue expression profiles of Hcy‐responsive Mt ETC genes. We found that these genes are differentially expressed among human and mouse, but most interesting is that the expression patterns of five ETC genes in heart tissue are conserved in both species. We screened the Hcy‐responsive genes using GEO profile database and confirmed the correlation of some of the genes by Hcy. Our results demonstrate for the first time that HHcy may impair Mt Com I and disrupt Mt ETC, which contributes to increased Mt reactive oxygen species (ROS) and CVD.