Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion

Chun Mei Cao, Wing Yee Yan, Jing Liu, Kenneth WL Kam, Shi Zhong Zhan, James Sham, Tak Ming Wong

Research output: Contribution to journalArticle

Abstract

Aim: Attenuation of mitochondrial Ca2+ ([Ca2+] m), but not cytosolic Ca2+ ([Ca2+] c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+] c, overload confers cardioprotection against ischemia/reperfusion- induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca 2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca 2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca 2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.

Original languageEnglish (US)
Pages (from-to)911-918
Number of pages8
JournalActa Pharmacologica Sinica
Volume27
Issue number7
DOIs
StatePublished - Jul 2006

Fingerprint

Ruthenium Red
Reperfusion Injury
Recovery
Reperfusion
Rats
Ischemia
Chelating Agents
Muscle Cells
Cell Survival
Cells
Wounds and Injuries
1,2-bis(2-aminophenoxy)ethane N,N,N',N'-tetraacetic acid acetoxymethyl ester

Keywords

  • BAPTA-AM
  • Cardiac myocytes
  • Electrically-induced Ca transient
  • Infarct size
  • Isolated perfused rat heart
  • Ruthenium red

ASJC Scopus subject areas

  • Chemistry(all)
  • Pharmacology

Cite this

Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion. / Cao, Chun Mei; Yan, Wing Yee; Liu, Jing; WL Kam, Kenneth; Zhan, Shi Zhong; Sham, James; Wong, Tak Ming.

In: Acta Pharmacologica Sinica, Vol. 27, No. 7, 07.2006, p. 911-918.

Research output: Contribution to journalArticle

Cao, Chun Mei ; Yan, Wing Yee ; Liu, Jing ; WL Kam, Kenneth ; Zhan, Shi Zhong ; Sham, James ; Wong, Tak Ming. / Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion. In: Acta Pharmacologica Sinica. 2006 ; Vol. 27, No. 7. pp. 911-918.
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abstract = "Aim: Attenuation of mitochondrial Ca2+ ([Ca2+] m), but not cytosolic Ca2+ ([Ca2+] c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+] c, overload confers cardioprotection against ischemia/reperfusion- induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca 2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca 2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca 2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.",
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T1 - Attenuation of mitochondrial, but not cytosolic, Ca2+ overload reduces myocardial injury induced by ischemia and reperfusion

AU - Cao, Chun Mei

AU - Yan, Wing Yee

AU - Liu, Jing

AU - WL Kam, Kenneth

AU - Zhan, Shi Zhong

AU - Sham, James

AU - Wong, Tak Ming

PY - 2006/7

Y1 - 2006/7

N2 - Aim: Attenuation of mitochondrial Ca2+ ([Ca2+] m), but not cytosolic Ca2+ ([Ca2+] c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+] c, overload confers cardioprotection against ischemia/reperfusion- induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca 2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca 2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca 2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.

AB - Aim: Attenuation of mitochondrial Ca2+ ([Ca2+] m), but not cytosolic Ca2+ ([Ca2+] c), overload improves contractile recovery. We hypothesized that attenuation of [Ca2+]m, but not [Ca2+] c, overload confers cardioprotection against ischemia/reperfusion- induced injury. Methods: Infarct size from isolated perfused rat heart, cell viability, and electrically-induced Ca2+ transient in isolated rat ventricular myocytes were measured. We determined the effects of BAPTA-AM, a Ca2+ chelator, at concentrations that abolish the overload of both [Ca2+]c and [Ca2+]m, and ruthenium red, an inhibitor of mitochondrial uniporter of Ca2+ transport, at concentrations that abolish the overload of [Ca2+]m, but not [Ca2+]c, on cardiac injury induced by ischemia/reperfusion. Results: Attenuation of both [Ca2+]m and [Ca2+]c by BAPTA-AM, and attenuation of [Ca 2+]m, but not [Ca2+]c, overload by ruthenium red, reduced the cardiac injury observations, indicating the importance of [Ca2+]m in cardioprotection and contractile recovery in response to ischemia/reperfusion. Conclusion: The study has provided unequivocal evidence using a cause-effect approach that attenuation of [Ca 2+]m, but not [Ca2+]c, overload is responsible for cardioprotection against ischemia/reperfusion-induced injury. We also confirmed the previous observation that attenuation of [Ca 2+]m, but not [Ca2+]c, by ruthenium red improves contractile recovery following ischemia/reperfusion.

KW - BAPTA-AM

KW - Cardiac myocytes

KW - Electrically-induced Ca transient

KW - Infarct size

KW - Isolated perfused rat heart

KW - Ruthenium red

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