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All-trans retinoic acid prevents angiotensin II- and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis.
J Cell Physiol. 2008 Apr; 215(1):172-81.JC

Abstract

Cardiomyocyte apoptosis has an important role in the transition from compensatory cardiac remodeling to heart failure. All-trans retinoic acid (RA), a bioactive vitamin A derivative, prevents stretch- and angiotensin II (Ang II)-induced cardiac hypertrophy. However, the anti-apoptotic potential of RA in the heart remains unexplored. Here, we demonstrate that stretch- and Ang II-induced apoptosis is prevented by RA in neonatal cardiomyocytes. RA improved mitochondrial function by inhibiting the stretch- and Ang II-induced reduction in mitochondrial membrane potential, cytochrome c release and by increasing the Bcl2/Bax ratio. RA inhibited stretch- and Ang II-induced intracellular reactive oxygen species (ROS) generation and upregulated the SOD2 level. Hydrogen peroxide-induced increases in the number of TUNEL-positive cells and percentage of Annexin V positive cells, were dose-dependently inhibited by RA. The thiol antioxidant, N-acetyl cysteine (NAC), completely inhibited stretch- and Ang II-induced apoptosis. Using diazoxide (mitochondrial ATP-sensitive K(+) channel opener) and SDS (NADPH oxidase activator), we confirmed that RA suppressed both mitochondrial- and NADPH oxidase-derived ROS. We also observed that both RAR and RXR were involved in preventing Ang II- and stretch-induced ROS production and apoptosis, by using selective retinoid receptor agonists and antagonists. Our data provide the first evidence that RA prevents Ang II and stretch induced apoptosis, by inhibiting ROS generation and increasing the anti-oxidant defense system, suggesting that RA-mediated signaling may provide a new therapeutic target for the prevention of the cardiac remodeling process.

Authors+Show Affiliations

Cardiovascular Research Institute, Texas A&M University System Health Science Center, College of Medicine, Temple, Texas 76504, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17941088

Citation

Choudhary, Rashmi, et al. "All-trans Retinoic Acid Prevents Angiotensin II- and Mechanical Stretch-induced Reactive Oxygen Species Generation and Cardiomyocyte Apoptosis." Journal of Cellular Physiology, vol. 215, no. 1, 2008, pp. 172-81.
Choudhary R, Baker KM, Pan J. All-trans retinoic acid prevents angiotensin II- and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis. J Cell Physiol. 2008;215(1):172-81.
Choudhary, R., Baker, K. M., & Pan, J. (2008). All-trans retinoic acid prevents angiotensin II- and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis. Journal of Cellular Physiology, 215(1), 172-81.
Choudhary R, Baker KM, Pan J. All-trans Retinoic Acid Prevents Angiotensin II- and Mechanical Stretch-induced Reactive Oxygen Species Generation and Cardiomyocyte Apoptosis. J Cell Physiol. 2008;215(1):172-81. PubMed PMID: 17941088.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - All-trans retinoic acid prevents angiotensin II- and mechanical stretch-induced reactive oxygen species generation and cardiomyocyte apoptosis. AU - Choudhary,Rashmi, AU - Baker,Kenneth M, AU - Pan,Jing, PY - 2007/10/18/pubmed PY - 2008/2/20/medline PY - 2007/10/18/entrez SP - 172 EP - 81 JF - Journal of cellular physiology JO - J Cell Physiol VL - 215 IS - 1 N2 - Cardiomyocyte apoptosis has an important role in the transition from compensatory cardiac remodeling to heart failure. All-trans retinoic acid (RA), a bioactive vitamin A derivative, prevents stretch- and angiotensin II (Ang II)-induced cardiac hypertrophy. However, the anti-apoptotic potential of RA in the heart remains unexplored. Here, we demonstrate that stretch- and Ang II-induced apoptosis is prevented by RA in neonatal cardiomyocytes. RA improved mitochondrial function by inhibiting the stretch- and Ang II-induced reduction in mitochondrial membrane potential, cytochrome c release and by increasing the Bcl2/Bax ratio. RA inhibited stretch- and Ang II-induced intracellular reactive oxygen species (ROS) generation and upregulated the SOD2 level. Hydrogen peroxide-induced increases in the number of TUNEL-positive cells and percentage of Annexin V positive cells, were dose-dependently inhibited by RA. The thiol antioxidant, N-acetyl cysteine (NAC), completely inhibited stretch- and Ang II-induced apoptosis. Using diazoxide (mitochondrial ATP-sensitive K(+) channel opener) and SDS (NADPH oxidase activator), we confirmed that RA suppressed both mitochondrial- and NADPH oxidase-derived ROS. We also observed that both RAR and RXR were involved in preventing Ang II- and stretch-induced ROS production and apoptosis, by using selective retinoid receptor agonists and antagonists. Our data provide the first evidence that RA prevents Ang II and stretch induced apoptosis, by inhibiting ROS generation and increasing the anti-oxidant defense system, suggesting that RA-mediated signaling may provide a new therapeutic target for the prevention of the cardiac remodeling process. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/17941088/All_trans_retinoic_acid_prevents_angiotensin_II__and_mechanical_stretch_induced_reactive_oxygen_species_generation_and_cardiomyocyte_apoptosis_ L2 - https://doi.org/10.1002/jcp.21297 DB - PRIME DP - Unbound Medicine ER -