Mitochondrial Oxidative Stress, DNA Damage, and Heart Failure

2006 ◽  
Vol 8 (9-10) ◽  
pp. 1737-1744 ◽  
Author(s):  
Hiroyuki Tsutsui ◽  
Tomomi Ide ◽  
Shintaro Kinugawa
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Dna Damage ◽  
Mitochondrial Oxidative Stress

scholarly journals Dynamic Compartmentalization of Base Excision Repair Proteins in Response to Nuclear and Mitochondrial Oxidative Stress

2008 ◽  
Vol 29 (3) ◽  
pp. 794-807 ◽  
Author(s):  
Lyra M. Griffiths ◽  
Dan Swartzlander ◽  
Kellen L. Meadows ◽  
Keith D. Wilkinson ◽  
Anita H. Corbett ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Damage ◽  
Dna Repair ◽  
Base Excision Repair ◽  
Oxidative Dna Damage ◽  
Excision Repair ◽  
Intracellular Localization ◽  
Genotoxic Stress ◽  
Mitochondrial Oxidative Stress ◽  
Base Excision

ABSTRACT DNAs harbored in both nuclei and mitochondria of eukaryotic cells are subject to continuous oxidative damage resulting from normal metabolic activities or environmental insults. Oxidative DNA damage is primarily reversed by the base excision repair (BER) pathway, initiated by N-glycosylase apurinic/apyrimidinic (AP) lyase proteins. To execute an appropriate repair response, BER components must be distributed to accommodate levels of genotoxic stress that may vary considerably between nuclei and mitochondria, depending on the growth state and stress environment of the cell. Numerous examples exist where cells respond to signals, resulting in relocalization of proteins involved in key biological transactions. To address whether such dynamic localization contributes to efficient organelle-specific DNA repair, we determined the intracellular localization of the Saccharomyces cerevisiae N-glycosylase/AP lyases, Ntg1 and Ntg2, in response to nuclear and mitochondrial oxidative stress. Fluorescence microscopy revealed that Ntg1 is differentially localized to nuclei and mitochondria, likely in response to the oxidative DNA damage status of the organelle. Sumoylation is associated with targeting of Ntg1 to nuclei containing oxidative DNA damage. These studies demonstrate that trafficking of DNA repair proteins to organelles containing high levels of oxidative DNA damage may be a central point for regulating BER in response to oxidative stress.

scholarly journals Oxidative Stress and Mitochondrial DNA Damage in Heart Failure

2008 ◽  
Vol 72 (SupplementA) ◽  
pp. A31-A37 ◽  
Author(s):  
Hiroyuki Tsutsui ◽  
Shintaro Kinugawa ◽  
Shouji Matsushima
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Dna Damage ◽  
Mitochondrial Dna ◽  
Mitochondrial Dna Damage

scholarly journals Mitochondrial Oxidative Stress Mediates Angiotensin II–Induced Cardiac Hypertrophy and Gαq Overexpression–Induced Heart Failure

2011 ◽  
Vol 108 (7) ◽  
pp. 837-846 ◽  
Author(s):  
Dao-Fu Dai ◽  
Simon C. Johnson ◽  
Jason J. Villarin ◽  
Michael T. Chin ◽  
Madeline Nieves-Cintrón ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Angiotensin Ii ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Oxidative Stress

scholarly journals Restore mitophagy is essential to prevent cardiac oxidative stress during hypertrophy

2021 ◽  
Author(s):  
Victoriane Peugnet ◽  
Maggy Chwastyniak ◽  
Steve Lancel ◽  
Laurent Bultot ◽  
Natacha Fourny ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Mitochondrial Biogenesis ◽  
Targeted Therapies ◽  
Superoxide Anion ◽  
Cardiomyocyte Hypertrophy ◽  
Mitochondrial Oxidative Stress ◽  
Mitochondrial Superoxide ◽  
The Impact

AbstractHeart failure, mostly associated with cardiac hypertrophy, is still a major cause of illness and death. Oxidative stress causes contractile failure and the accumulation of reactive oxygen species leads to mitochondrial dysfunction, associated with aging and heart failure, suggesting that mitochondria-targeted therapies could be effective in this context. The purpose of this work was to characterize how mitochondrial oxidative stress is involved in cardiac hypertrophy development and to determine if mitochondria-targeted therapies could improve cardiac phenotypes. We used neonatal and adult rat cardiomyocytes (NCMs and ACMs) hypertrophied by isoproterenol (Iso) to induce an increase of mitochondrial superoxide anion. Superoxide dismutase 2 activity and mitochondrial biogenesis were significantly decreased after 24h of Iso treatment. To counteract the mitochondrial oxidative stress induced by hypertrophy, we evaluated the impact of two different anti-oxidants, mitoquinone (MitoQ) and EUK 134. Both significantly decreased mitochondrial superoxide anion and hypertrophy in hypertrophied NCMs and ACMs. Conversely to EUK 134 which preserved cell functions, MitoQ impaired mitochondrial function by decreasing maximal mitochondrial respiration, mitochondrial membrane potential and mitophagy (particularly Parkin expression) and altering mitochondrial structure. The same decrease of Parkin was found in human cardiomyocytes but not in fibroblasts suggesting a cell specificity deleterious effect of MitoQ. Our data showed the importance of mitochondrial oxidative stress in the development of cardiomyocyte hypertrophy. Interestingly, we observed that targeting mitochondria by an anti-oxidant (MitoQ) impaired metabolism specifically in cardiomyocytes. Conversely, the SOD mimic (EUK 134) decreased both oxidative stress and cardiomyocyte hypertrophy and restored impaired cardiomyocyte metabolism and mitochondrial biogenesis.

Abstract 15796: Increased Cardiac Heme Levels Through Cardiac Overexpression of Delta-aminolevulinic Acid Synthase 2 (ALAS2) Lead to Exacerbated Ischemic Injury

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Konrad T Sawicki ◽  
Meng Shang ◽  
Rongxue Wu ◽  
Hsiang-Chun Chang ◽  
Arineh Khechaduri ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Cell Death ◽  
Transgenic Mice ◽  
Cardiac Function ◽  
Ischemic Cardiomyopathy ◽  
Aminolevulinic Acid ◽  
Causative Role ◽  
Mitochondrial Oxidative Stress ◽  
Coronary Ligation

Introduction: Heme is an essential iron-containing molecule for cardiovascular physiology, but in excess it may increase oxidative stress. Failing human hearts have increased heme levels, with upregulation of the rate-limiting enzyme in heme synthesis, δ-aminolevulinic acid synthase 2 (ALAS2), which is normally not expressed in cardiomyocytes. Hypothesis: We hypothesized that increased heme accumulation (through cardiac overexpression of ALAS2) leads to increased oxidative stress and cell death in the heart. Results: We first showed that ALAS2 and heme levels are increased in the hearts of mice subjected to coronary ligation. To determine the causative role of increased heme in the development of heart failure, we generated transgenic mice with cardiac-specific overexpression of ALAS2. While ALAS2 transgenic mice have normal cardiac function at baseline, their hearts display increased heme content, higher oxidative stress, exacerbated cell death, and worsened cardiac function after coronary ligation compared to non-transgenic littermates. We confirmed in cultured cardiomyoblasts that the increased oxidative stress and cell death by ALAS2 overexpression is mediated by increased heme accumulation. Furthermore, knockdown of ALAS2 in cultured cardiomyoblasts exposed to hypoxia reversed the increases in heme content and cell death. Administration of the mitochondrial antioxidant MitoTempo to ALAS2-overexpressing cardiomyoblasts normalized the elevated oxidative stress and cell death levels to baseline, indicating that the effects of increased ALAS2 and heme are through elevated mitochondrial oxidative stress. The clinical relevance of these findings was supported by the finding of increased ALAS2 induction and heme accumulation in failing human hearts from patients with ischemic cardiomyopathy compared to non-ischemic cardiomyopathy. Conclusions: Heme accumulation is detrimental to cardiac function under ischemic conditions, and reducing heme in the heart may be a novel approach for protection against the development of heart failure.

The influence of low-level laser therapy on parameters of oxidative stress and DNA damage on muscle and plasma in rats with heart failure

2014 ◽  
Vol 29 (6) ◽  
pp. 1895-1906 ◽  
Author(s):  
Micheli Biasibetti ◽  
Denise B. Rojas ◽  
Vítor S. Hentschke ◽  
Dinara Jaqueline Moura ◽  
Marlus Karsten ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Heart Failure ◽  
Dna Damage ◽  
Laser Therapy ◽  
Low Level Laser Therapy ◽  
Low Level ◽  
Low Level Laser ◽  
Level Laser
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