Antioxidants and phase 2 enzymes in cardiomyocytes: Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury

Zhuoxiao Cao, Hong Zhu, Li Zhang, Xue Zhao, Jay L. Zweier, Yunbo Li

Research output: Contribution to journalArticle

Abstract

The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, γ-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.

Original languageEnglish (US)
Pages (from-to)1353-1364
Number of pages12
JournalExperimental Biology and Medicine
Volume231
Issue number8
StatePublished - 2006
Externally publishedYes

Fingerprint

Thiones
Reperfusion Injury
Cardiac Myocytes
Oxidants
Antioxidants
Enzymes
Glutathione Reductase
Wounds and Injuries
Catalase
Reperfusion
Messenger RNA
Ischemia
Oxidative stress
Ligases
Glutathione
Rats
Oxidoreductases
Cells
Peroxidase
Oxygen

Keywords

  • 3H-1,2-dithiole-3-thione
  • Antioxidants
  • Cardiac cells
  • Cytotoxicity
  • Oxidants
  • Simulated ischemia-reperfusion

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Antioxidants and phase 2 enzymes in cardiomyocytes : Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury. / Cao, Zhuoxiao; Zhu, Hong; Zhang, Li; Zhao, Xue; Zweier, Jay L.; Li, Yunbo.

In: Experimental Biology and Medicine, Vol. 231, No. 8, 2006, p. 1353-1364.

Research output: Contribution to journalArticle

Cao, Zhuoxiao ; Zhu, Hong ; Zhang, Li ; Zhao, Xue ; Zweier, Jay L. ; Li, Yunbo. / Antioxidants and phase 2 enzymes in cardiomyocytes : Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury. In: Experimental Biology and Medicine. 2006 ; Vol. 231, No. 8. pp. 1353-1364.
@article{79518f91ab0f4ff4a59a7f72aeecccb5,
title = "Antioxidants and phase 2 enzymes in cardiomyocytes: Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury",
abstract = "The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, γ-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.",
keywords = "3H-1,2-dithiole-3-thione, Antioxidants, Cardiac cells, Cytotoxicity, Oxidants, Simulated ischemia-reperfusion",
author = "Zhuoxiao Cao and Hong Zhu and Li Zhang and Xue Zhao and Zweier, {Jay L.} and Yunbo Li",
year = "2006",
language = "English (US)",
volume = "231",
pages = "1353--1364",
journal = "Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)",
issn = "0037-9727",
publisher = "Society for Experimental Biology and Medicine",
number = "8",

}

TY - JOUR

T1 - Antioxidants and phase 2 enzymes in cardiomyocytes

T2 - Chemical inducibility and chemoprotection against oxidant and simulated ischemia-reperfusion injury

AU - Cao, Zhuoxiao

AU - Zhu, Hong

AU - Zhang, Li

AU - Zhao, Xue

AU - Zweier, Jay L.

AU - Li, Yunbo

PY - 2006

Y1 - 2006

N2 - The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, γ-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.

AB - The increasing recognition of the role for oxidative stress in cardiac disorders has led to extensive investigation on the protection by exogenous antioxidants against oxidative cardiac injury. On the other hand, another strategy for protecting against oxidative cardiac injury may be through upregulation of the endogenous antioxidants and phase 2 enzymes in the myocardium by chemical inducers. However, our current understanding of the chemical inducibility of cardiac cellular antioxidants and phase 2 enzymes is very limited. In this study, using rat cardiac H9c2 cells we have characterized the concentration- and time-dependent induction of cellular antioxidants and phase 2 enzymes by 3H-1,2-dithiole-3-thione (D3T), and the resultant chemoprotective effects on oxidative cardiac cell injury. Incubation of H9c2 cells with D3T resulted in a marked concentration-and time-dependent induction of a number of cellular antioxidants and phase 2 enzymes, including catalase, reduced glutathione (GSH), GSH peroxidase, glutathione reductase (GR), GSH S-transferase (GST), and NAD(P)H:quinone oxidoreductase-1 (NQO1). D3T treatment of H9c2 cells also caused an increase in mRNA expression of catalase, γ-glutamylcysteine ligase catalytic subunit, GR, GSTA1, M1 and P1, and NQO1. Moreover, both mRNA and protein expression of Nrf2 were induced in D3T-treated cells. D3T pretreatment led to a marked protection against H9c2 cell injury elicited by various oxidants and simulated ischemia-reperfusion. D3T pretreatment also resulted in decreased intracellular accumulation of reactive oxygen in H9c2 cells after exposure to the oxidants as well as simulated ischemia-reperfusion. This study demonstrates that a series of endogenous antioxidants and phase 2 enzymes in H9c2 cells can be induced by D3T in a concentration- and time-dependent fashion, and that the D3T-upregulated cellular defenses are accompanied by a markedly increased resistance to oxidative cardiac cell injury.

KW - 3H-1,2-dithiole-3-thione

KW - Antioxidants

KW - Cardiac cells

KW - Cytotoxicity

KW - Oxidants

KW - Simulated ischemia-reperfusion

UR - http://www.scopus.com/inward/record.url?scp=33748288140&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33748288140&partnerID=8YFLogxK

M3 - Article

C2 - 16946404

AN - SCOPUS:33748288140

VL - 231

SP - 1353

EP - 1364

JO - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

JF - Proceedings of the Society for Experimental Biology and Medicine. Society for Experimental Biology and Medicine (New York, N. Y.)

SN - 0037-9727

IS - 8

ER -