Apoptosis and oxidants in the heart

Kumar, Dinesh; Jugdutt, Bodh I.

doi:10.1016/s0022-2143(03)00148-3

Cited by 207 publications

(142 citation statements)

References 61 publications

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“…After myocardial infarction and reperfusion, reactive oxygen species (ROS) are generated in the ischemic myocardium and directly cause apoptosis. The in vivo oxidative stressinduced apoptosis can be simulated in vitro by H 2 O 2 treatment of both isolated adult cardiomyocytes and MSCs (Kumar and Jugdutt, 2003;Pasha et al, 2008). In the present study, we have shown that SDF-1 pretreatment can protect MSCs from H 2 O 2 -induced damages.…”

Section: Discussionsupporting

confidence: 54%

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

et al. 2011

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Bone marrow mesenchymal stem cells (MSCs) are considered as a promising cell source to treat the acute myocardial infarction. However, over 90% of the stem cells usually die in the first three days of transplantation. Survival potential, migration ability and paracrine capacity have been considered as the most important three factors for cell transplantation in the ischemic cardiac treatment. We hypothesized that stromal-derived factor-1 (SDF-1)/CXCR4 axis plays a critical role in the regulation of these processes. In this study, apoptosis was induced by exposure of MSCs to H 2 O 2 for 2 h. After re-oxygenation, the SDF-1 pretreated MSCs demonstrated a significant increase in survival and proliferation. SDF-1 pretreatment also enhanced the migration and increased the secretion of pro-survival and angiogenic cytokines including basic fibroblast growth factor and vascular endothelial growth factor. Western blot and RT-PCR demonstrated that SDF-1 pretreatment significantly activated the pro-survival Akt and Erk signaling pathways and up-regulated Bcl-2/Bax ratio. These protective effects were partially inhibited by AMD3100, an antagonist of CXCR4. We conclude that the SDF-1/CXCR4 axis is critical for MSC survival, migration and cytokine secretion.

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Section: Discussionsupporting

confidence: 54%

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

et al. 2011

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“…ROS have been proven to be one of the stimulators of myocyte apoptosis (35)(36)(37). Treatment with the antioxidants has been indicated to attenuate oxidative stress and cardiomyocyte apoptosis (38)(39)(40). Following MI, myocardial hypertrophy is developed in non-infarcted left ventricle, which is most evident at week 4.…”

Section: Discussionmentioning

confidence: 99%

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Zhao¹,

Zhao²,

Yan³

et al. 2009

Cardiovascular Pathology

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Background-There is growing recognition that oxidative stress plays a role in the pathogeneses of myocardial repair/remodeling following infarction (MI). NADPH oxidase is a major source for cardiac reactive oxygen species production. Herein, we studied the importance of NADPH oxidase in development of cardiac oxidative stress and its induced molecular and cellular changes related to myocardial repair/remodeling.

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“…Increased production of ROS is implicated in loss of mitochondrial membrane potential (MP) (ΔΨ m ) [Leist et al, 1997;Crompton, 1999] and induction of members of Bcl 2 protein family. Mitochondrial releases cytochrome-c and caspases that leads to eventual endothelial cell apoptosis and cardiac dysfunction [Kumar and Jugdutt, 2003].Apoptosis or programmed cell death, an evolutionarily conserved and genetically controlled active cell suicide process, maintains cellular and tissue homeostasis of multicellular organisms. Apoptosis can be initiated through two pathways.…”

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confidence: 99%

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confidence: 99%

Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia

Tyagi

Ovechkin

Lominadze

et al. 2006

J of Cellular Biochemistry

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An elevated level of homocysteine (Hcy) limits the growth and induces apoptosis. However, the mechanism of Hcy-induced programmed cell death in endothelial cells is largely unknown. We hypothesize that Hcy induces intracellular reactive oxygen species (ROS) production that leads to the loss of transmembrane mitochondrial potential (Δψ m ) accompanied by the release of cytochrome-c from mitochondria. Cytochrome-c release contributes to caspase activation, such as caspase-9, caspase-6, and caspase-3, which results in the degradation of numerous nuclear proteins including poly (ADP-ribose) polymerase (PARP), which subsequently leads to the internucleosomal cleavage of DNA, resulting cell death. In this study, rat heart microvascular endothelial cells (MVEC) were treated with different doses of Hcy at different time intervals. Apoptosis was measured by DNA laddering and transferase-mediated dUTP nick-end labeling (TUNEL) assay. ROS production and MP were determined using florescent probes (2,7-dichlorofluorescein (DCFH-DA) and 5,5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzamidazolocarbocyanin iodide (JC-1), respectively, by confocal microscopy. Differential gene expression for apoptosis was analyzed by cDNA array. The results showed that Hcy-mediated ROS production preceded the loss of MP, the release of cytochrome-c, and the activation of caspase-9 and -3. Moreover the Hcy treatment resulted in a decrease in Bcl 2 /Bax ratio, evaluated by mRNA levels. Caspase-9 and -3 were activated, causing cleavage of PARP, a hallmark of apoptosis and internucleosomal DNA fragmentation. The cytotoxic effect of Hcy was blocked by using small interfering RNA (siRNA)-mediated suppression of caspase-9 in MVEC. Suppressing the activation of caspase-9 inhibited the activation of caspase -3 and enhanced the cell viability and MP. Our data suggested that Hcy-mediated ROS production promotes endothelial cell death in part by disturbing MP, which results in subsequent release of cytochrome-c and activation of caspase-9 and 3, leading to cell death. KeywordsPARP; cytochrome-c; reactive oxygen species; siRNA; cardiac microvascular endothelial cells; oxidative stress; mitochondrial membrane potential; siRNA; cDNA array; TUNEL; Bax; Bcl 2 ; caspase Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, stroke, and peripheral vascular disease [Jacobsen, 1998;Hankey and Eikelboom, 1999;Fallon et al., 2001;Suhara et al., 2004] [Tsai et al., 1994].Hcy is a thiol-containing amino acid formed during the intracellular demethylation of methionine and causes multifold effects through the reactivity of its sufhydryl group. Increase in levels of Hcy impairs cellular function and leads to loss of endothelial antithrombotic function, lipid peroxidation, impairment of platelet aggregation, enhanced oxidative stress, and apoptosis (programmed cell death) [Blom et al., 1995;Tawakol et al., 1997;Carsten and Kenneth, 2004]. These unfavorable vascular effects of Hcy are a result of the generation of reactive oxygen species (ROS) [...

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Apoptosis and oxidants in the heart

Cited by 207 publications

References 61 publications

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

SDF-1/CXCR4 axis modulates bone marrow mesenchymal stem cell apoptosis, migration and cytokine secretion

Cardiac oxidative stress and remodeling following infarction: role of NADPH oxidase

Mitochondrial mechanism of microvascular endothelial cells apoptosis in hyperhomocysteinemia

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