Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner

Chae, Han-Jung; So, Hong-Seob; Chae, Soo‐Wan; Park, Ji-Sun; Kim, Myung‐Sun; Oh, Ji Hyun; Chung, Yeun Tai; Yang, Sei‐Hoon; Jeong, Eun Taik; Kim, Hyung-min; Park, Raekil; Kim, Hyung‐Ryong

doi:10.1016/s1567-5769(01)00033-9

Cited by 23 publications

(19 citation statements)

References 35 publications

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“…The finding of SNP-induced cell death in this study was consistent with previous reports in cardiomyocytes [23,[35][36][37] . SNP-induced cell death is mediated through NO, hydrogen peroxide and resultant peroxynitrite generated from the combination of NO and superoxide [23] .…”

Section: Discussionsupporting

confidence: 93%

Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death

Rabkin

Tsang²

2008

Pharmacology

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Aim: The objective of this study was to examine the interaction ofa 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitor (statin) with a nitric oxide (NO) donor from the perspective of the impact on cardiomyocyte cell viability. Methods: Embryonic chick cardiomyocytes in culture were treated with a wide range of concentrations of sodium nitroprusside (SNP), which releases NO and also generates toxic reactive nitrogen species. SNP was combined with the HMG-CoA reductase inhibitor lovastatin and cell viability was assessed by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide] assay. Results: SNP and lovastatin each produced a significant (p < 0.01) concentration-dependent increase in cell death. Using SNP concentrations at or below the ED₅₀, SNP (0.01, 0.1 or 0.5 mmol/l) increased the amount of cell death when combined with lovastatin (1, 10, 50 and 100 µmol/l). At lovastatin concentrations of 50 µmol/l and less, the amount of cell death was consistently similar to the arithmetic sum of SNP and lovastatin, suggesting that there was an additive and not synergistic relationship between SNP and lovastatin. In combination with lovastatin (100 µmol/l), however, the amount of cell death was consistently lower than the calculated expected value and suggested saturation of a common mechanism. The combination of SNP and lovastatin produced the characteristic microscopic changes of apoptosis. Considering that both SNP and lovastatin can activate caspase-3, cells were treated with the caspase-3 inhibitor Ac-DEVD-CHO. This inhibitor produced a significant (p < 0.05) and consistent 30% reduction in the amount of cell death induced by SNP and lovastatin. Conclusion: These data suggest that the cardiomyocyte toxicity from NO continues to be evident uninterrupted by and not accentuated by the presence of an HMG-CoA inhibitor. The cardiac adverse effect of each of these agents utilizes a common pathway involving caspase-3 so that their cardiotoxicity can be blunted by a caspase-3 inhibitor.

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Section: Discussionsupporting

confidence: 93%

Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death

Rabkin

Tsang²

2008

Pharmacology

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“…Although our objective was not to determine the efficiency of the enzymatic transformation of TCE into TCAA, our experimental data show that the H9c2 cells are responsive to very low doses of TCE (10 ppb = 76 nmol/L) and TCAA (10 ppb = 6 nmol/L), have the enzymatic ability to metabolize TCE, and therefore can be used as a model to study sensitivity and responsiveness to these toxicants. The usefulness of this cell line as a model for studying the relationship between myogenic differentiation and exposure to toxicants has been documented by several other groups (Menard et al, 1999;Chae et al, 2001;Chen et al, 2003;Kashour et al, 2003). Our own findings confirm that the H9c2 cells provide a suitable model for study of the molecular mechanisms of TCE cardiac toxicity, especially when compared with the results obtained using the rat hepatoma cell line H4IIE.…”

Section: Discussionsupporting

confidence: 83%

Effects of trichloroethylene and its metabolite trichloroacetic acid on the expression of vimentin in the rat H9c2 cell line

et al. 2005

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Trichloroethylene (TCE) and its metabolite trichloroacetic acid (TCAA) are environmental contaminants with specific toxicity for the embryonic heart. In an effort to identify the cellular pathways disrupted by TCE and TCAA during heart development, we investigated their effects on expression of vimentin, a marker of cardiac differentiation. Previous studies had shown that the level of vimentin transcript was inhibited in rat embryonic heart after maternal exposure to TCE via drinking water. In the same study, maternal exposure to TCAA produced the opposite effect, inducing an increased level of vimentin mRNA. In this study, we selected an in vitro system, the rat cardiac myoblast cell line H9c2, to further characterize the molecular mechanisms used by TCE and TCAA to disrupt normal heart development. In particular, we investigated the effects of both toxicants on vimentin, at both the RNA and protein levels, using dose-response and time course curves. Our experimental findings indicate that vimentin expression is affected by TCE and TCAA in H9c2 cells similarly as in vivo. The work is significant because it provides a suitable in vitro model for studies looking at toxicant effects on myocardiac cells, and it suggests that vimentin is a good marker of TCE exposure in the embryonic heart.

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“…46 A gross simplification implies that p38 and/or JNK activation conveys a proapoptotic NO signal that will provoke p53 accumulation, caspase activation and cell dissolution. [47][48][49][50][51][52] Besides, protein kinase C modulates NO-elicited cell death. 53,54 Unfortunately, inhibition of PKC is either correlated with attenuated apoptosis or its enhancement, including p53 accumulation, in the case of PKCa or PKC-z inhibition, while PKC-e may promote NOinduced damage to colonic mucosal cells.…”

Section: No Evoked Accumulation Of P53mentioning

confidence: 99%

Nitric oxide: NO apoptosis or turning it ON?

2003

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Nitric oxide (NO) is known for its diverse activities throughout biology. Among signaling qualities, NO affects cellular decisions of life and death either by turning on apoptotic pathways or by shutting them off. Although copious reports support both notions, the dichotomy of NO actions remains unsolved. Proapoptotic pathways of NO are compatible with established signaling circuits appreciated for mitochondriadependent roads of death, with some emphasis on the involvement of the tumor suppressor p53 as a target during cell death execution. Antiapoptotic actions of NO are numerous, ranging from an immediate interference with proapoptotic signaling cascades to long-lasting effects based on expression of cell protective proteins with some interest on the ability of NO-redox species to block caspases by Snitrosylation/S-nitrosation. Summarizing emerging concepts to understand p53 accumulation on the one hand while proposing inhibition of procaspase processing on the other may help to define the pro-versus antiapoptotic roles of NO.

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Sodium nitroprusside induces apoptosis of H9C2 cardiac muscle cells in a c-Jun N-terminal kinase-dependent manner

Cited by 23 publications

References 35 publications

Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death

Interaction of the HMG-CoA Reductase Inhibitor Lovastatin and Nitric Oxide in Cardiomyocyte Cell Death

Effects of trichloroethylene and its metabolite trichloroacetic acid on the expression of vimentin in the rat H9c2 cell line

Nitric oxide: NO apoptosis or turning it ON?

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