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Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway.
Toxicol Appl Pharmacol. 2009 Oct 01; 240(1):73-87.TA

Abstract

Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-kappaB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-kappaB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-kappaB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-kappaB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden.

Authors+Show Affiliations

Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054, West Bengal, India.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article

Language

eng

PubMed ID

19616567

Citation

Ghosh, Jyotirmoy, et al. "Taurine Prevents Arsenic-induced Cardiac Oxidative Stress and Apoptotic Damage: Role of NF-kappa B, P38 and JNK MAPK Pathway." Toxicology and Applied Pharmacology, vol. 240, no. 1, 2009, pp. 73-87.
Ghosh J, Das J, Manna P, et al. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway. Toxicol Appl Pharmacol. 2009;240(1):73-87.
Ghosh, J., Das, J., Manna, P., & Sil, P. C. (2009). Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway. Toxicology and Applied Pharmacology, 240(1), 73-87. https://doi.org/10.1016/j.taap.2009.07.008
Ghosh J, et al. Taurine Prevents Arsenic-induced Cardiac Oxidative Stress and Apoptotic Damage: Role of NF-kappa B, P38 and JNK MAPK Pathway. Toxicol Appl Pharmacol. 2009 Oct 1;240(1):73-87. PubMed PMID: 19616567.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: role of NF-kappa B, p38 and JNK MAPK pathway. AU - Ghosh,Jyotirmoy, AU - Das,Joydeep, AU - Manna,Prasenjit, AU - Sil,Parames C, Y1 - 2009/07/17/ PY - 2009/06/03/received PY - 2009/07/03/revised PY - 2009/07/07/accepted PY - 2009/7/21/entrez PY - 2009/7/21/pubmed PY - 2009/9/30/medline SP - 73 EP - 87 JF - Toxicology and applied pharmacology JO - Toxicol Appl Pharmacol VL - 240 IS - 1 N2 - Cardiac dysfunction is a major cause of morbidity and mortality worldwide due to its complex pathogenesis. However, little is known about the mechanism of arsenic-induced cardiac abnormalities and the use of antioxidants as the possible protective agents in this pathophysiology. Conditionally essential amino acid, taurine, accounts for 25% to 50% of the amino acid pool in myocardium and possesses antioxidant properties. The present study has, therefore, been carried out to investigate the underlying mechanism of the beneficial role of taurine in arsenic-induced cardiac oxidative damage and cell death. Arsenic reduced cardiomyocyte viability, increased reactive oxygen species (ROS) production and intracellular calcium overload, and induced apoptotic cell death by mitochondrial dependent caspase-3 activation and poly-ADP ribose polymerase (PARP) cleavage. These changes due to arsenic exposure were found to be associated with increased IKK and NF-kappaB (p65) phosphorylation. Pre-exposure of myocytes to an IKK inhibitor (PS-1145) prevented As-induced caspase-3 and PARP cleavage. Arsenic also markedly increased the activity of p38 and JNK MAPKs, but not ERK to that extent. Pre-treatment with SP600125 (JNK inhibitor) and SB203580 (p38 MAPK inhibitor) attenuated NF-kappaB and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-kappaB activation. Taurine treatment suppressed these apoptotic actions, suggesting that its protective role in arsenic-induced cardiomyocyte apoptosis is mediated by attenuation of p38 and JNK MAPK signaling pathways. Similarly, arsenic intoxication altered a number of biomarkers related to cardiac oxidative stress and other apoptotic indices in vivo and taurine supplementation could reduce it. Results suggest that taurine prevented arsenic-induced myocardial pathophysiology, attenuated NF-kappaB activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden. SN - 1096-0333 UR - https://www.unboundmedicine.com/medline/citation/19616567/Taurine_prevents_arsenic_induced_cardiac_oxidative_stress_and_apoptotic_damage:_role_of_NF_kappa_B_p38_and_JNK_MAPK_pathway_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0041-008X(09)00289-0 DB - PRIME DP - Unbound Medicine ER -