Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway
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-{kappa}B (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-{kappa}B and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-{kappa}B activation. Taurine treatment suppressed these apoptoticmore »
- Authors:
-
- Division of Molecular Medicine, Bose Institute, P-1/12, CIT Scheme VII M, Kolkata-700054, West Bengal (India)
- Publication Date:
- OSTI Identifier:
- 21272667
- Resource Type:
- Journal Article
- Journal Name:
- Toxicology and Applied Pharmacology
- Additional Journal Information:
- Journal Volume: 240; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2009.07.008; PII: S0041-008X(09)00289-0; Copyright (c) 2009 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0041-008X
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; APOPTOSIS; ARSENIC; BIOLOGICAL MARKERS; CALCIUM; CARDIOVASCULAR DISEASES; DISEASE INCIDENCE; IN VIVO; MITOCHONDRIA; MORTALITY; MYOCARDIUM; PATHOGENESIS; PHOSPHORYLATION; STRESSES; TAURINE
Citation Formats
Ghosh, Jyotirmoy, Das, Joydeep, Manna, Prasenjit, and Sil, Parames C. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway. United States: N. p., 2009.
Web. doi:10.1016/j.taap.2009.07.008.
Ghosh, Jyotirmoy, Das, Joydeep, Manna, Prasenjit, & Sil, Parames C. Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway. United States. https://doi.org/10.1016/j.taap.2009.07.008
Ghosh, Jyotirmoy, Das, Joydeep, Manna, Prasenjit, and Sil, Parames C. 2009.
"Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway". United States. https://doi.org/10.1016/j.taap.2009.07.008.
@article{osti_21272667,
title = {Taurine prevents arsenic-induced cardiac oxidative stress and apoptotic damage: Role of NF-{kappa}B, p38 and JNK MAPK pathway},
author = {Ghosh, Jyotirmoy and Das, Joydeep and Manna, Prasenjit and Sil, Parames C.},
abstractNote = {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-{kappa}B (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-{kappa}B and IKK phosphorylation indicating that p38 and JNK MAPKs are mainly involved in arsenic-induced NF-{kappa}B 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-{kappa}B activation via IKK, p38 and JNK MAPK signaling pathways and could possibly provide a protection against As-induced cardiovascular burden.},
doi = {10.1016/j.taap.2009.07.008},
url = {https://www.osti.gov/biblio/21272667},
journal = {Toxicology and Applied Pharmacology},
issn = {0041-008X},
number = 1,
volume = 240,
place = {United States},
year = {Thu Oct 01 00:00:00 EDT 2009},
month = {Thu Oct 01 00:00:00 EDT 2009}
}