Cardiac Aging in Mice and Humans: The Role of Mitochondrial Oxidative Stress

Introduction: Cardiac aging is the major risk factor for advanced heart disease, which is the leading cause of death in developed countries, accounting for >30% of deaths worldwide. Objective: To discover the detailed mechanism of cardiac aging and develop an effective therapeutic candidate drug to treat or delay cardiac aging. Methods: We used D-galactose to induce cardiac aging in Nrf2+/+ and Nrf2–/– mice, and then treated these mice with vehicle or the Nrf2 activator, CDDO-imidazolide (CDDO-Im). Results and Conclusions: D-galactose injection significantly induced cardiac aging, cell apoptosis, and oxidative stress in Nrf2+/+ mice, all of which were further exacerbated in Nrf2–/– mice. CDDO-Im treatment can effectively weaken oxidative stress and enhance the activities of antioxidant enzymes, but CDDO-Im lost its antioxidative effect in the Nrf2–/– mice. Nrf2 activator CDDO-Im could therefore effectively protect against D-galactose-induced cardiac aging by inhibiting oxidative stress, suggesting that CDDO-Im might be a potential and promising therapeutic candidate drug to treat cardiac aging.

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The pathophysiological role of mitochondrial oxidative stress in lung diseases

Journal of Translational Medicine ◽

10.1186/s12967-017-1306-5 ◽

2017 ◽

Vol 15 (1) ◽

Cited By ~ 40

Author(s):

Xiaojing Liu ◽

Zhihong Chen

Keyword(s):

Oxidative Stress ◽

Lung Diseases ◽

Mitochondrial Oxidative Stress ◽

Pathophysiological Role

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Role of mitochondrial oxidative stress in the apoptosis induced by diospyrin diethylether in human breast carcinoma (MCF-7) cells

Molecular and Cellular Biochemistry ◽

10.1007/s11010-008-9920-4 ◽

2008 ◽

Vol 320 (1-2) ◽

pp. 185-195 ◽

Cited By ~ 14

Author(s):

Binod Kumar ◽

Amit Kumar ◽

B. N. Pandey ◽

K. P. Mishra ◽

Banasri Hazra

Keyword(s):

Oxidative Stress ◽

Breast Carcinoma ◽

Human Breast Carcinoma ◽

Human Breast ◽

Mitochondrial Oxidative Stress ◽

Mcf 7

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Mitochondrial Oxidative Stress-Induced Epigenetic Modif ications in Pancreatic Epithelial Cells

International Journal of Toxicology ◽

10.1177/1091581814524064 ◽

2014 ◽

Vol 33 (2) ◽

pp. 116-129 ◽

Cited By ~ 19

Author(s):

Pradyumna Kumar Mishra ◽

Gorantla Venkata Raghuram ◽

Deepika Jain ◽

Subodh Kumar Jain ◽

Naveen Kumar Khare ◽

...

Keyword(s):

Oxidative Stress ◽

Epithelial Cells ◽

Histone Modifications ◽

Expression Patterns ◽

Fragile Sites ◽

Gene Promoters ◽

Mitochondrial Oxidative Stress ◽

Altered Expression ◽

Posttranslational Histone Modifications

Emerging studies have linked prooxidative carbamate compound exposures with various human pathologies including pancreatic cancer. In these studies, our aim was to examine mitochondrial oxidative stress-mediated aberrant chromatin responses in human pancreatic ductal epithelial cells. Posttranslational histone modifications, promoter DNA methylation, and micro-RNA (miRNA) expression patterns were evaluated following induction of mitochondrial oxidative stress by N-succinimidyl N-methylcarbamate exposure. In treated cells, perturbation in mitochondrial machinery led to hypermethylation of p16 and smad4 gene promoters and downregulation of respective gene products. Posttranslational histone modifications that include hypoacetylation of acetylated histone (AcH) 3 and AcH4, hypermethylation of monomethylated histone 3 at lysine 9 and trimethylated histone 4 at lysine 20 ubiquitinated histone (uH) 2A/uH2B, and increased phosphorylation of H2AX and H3 were observed in the treated cells. Altered expression of miRNAs denoted possible location of corresponding genes at oxidatively damaged fragile sites. Collectively, our results provide a direct role of mitochondrial oxidative stress-mediated epigenetic imbalance to perturbed genomic integrity in oxygen radical-induced pancreatic injury. Further, identification and characterization of molecular switches that affect these epigenomic signatures and targets thereof will be imperative to understand the complex role of redox-regulatory network in pancreatic milieu.

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