Initiation of mitochondrial-mediated apoptosis during cardiac reperfusion

Kathleen Corrigan Lundberg, Luke I. Szweda

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

Reperfusion of myocardial tissue can result in programmed cell death. Nevertheless, relatively little information exists concerning pathways initiated in vivo that ultimately commit cardiac cells to apoptosis during ischemia/reperfusion. The goal of the present study was to determine whether mitochondrial-mediated mechanisms of apoptosis are initiated during in vivo cardiac ischemia/reperfusion. We provide evidence that the content of cytochrome c in the cytosol increases exclusively during reperfusion. Over the same time interval Bax, a pro-apoptotic protein implicated in release of cytochrome c from mitochondria, was found to disappear from cytosolic extracts. This was associated with the appearance of tightly associated Bax in the mitochondrial fraction. Cytochrome c from reperfused cytosolic extracts is present as a high molecular weight oligomer consistent with formation of the apoptosome. In addition, pro-caspase-9 was found to disappear exclusively during reperfusion. Therefore, the results of the current study indicate that the mitochondrial-mediated pathway of apoptosis is initiated as a result of in vivo cardiac ischemia/reperfusion.

Original languageEnglish (US)
Pages (from-to)50-57
Number of pages8
JournalArchives of Biochemistry and Biophysics
Volume432
Issue number1
DOIs
StatePublished - Dec 1 2004

Fingerprint

Cytochromes c
Reperfusion
Apoptosis
Ischemia
Apoptosis Regulatory Proteins
Mitochondria
Caspase 9
Cell death
Oligomers
Apoptosomes
Molecular weight
Myocardial Reperfusion
Tissue
Cytosol
Cell Death
Molecular Weight

Keywords

  • Apoptosis
  • Bax
  • Cytochrome c
  • Heart
  • Ischemia
  • Mitochondria
  • Reperfusion

ASJC Scopus subject areas

  • Biochemistry
  • Biophysics
  • Molecular Biology

Cite this

Initiation of mitochondrial-mediated apoptosis during cardiac reperfusion. / Lundberg, Kathleen Corrigan; Szweda, Luke I.

In: Archives of Biochemistry and Biophysics, Vol. 432, No. 1, 01.12.2004, p. 50-57.

Research output: Contribution to journalArticle

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N2 - Reperfusion of myocardial tissue can result in programmed cell death. Nevertheless, relatively little information exists concerning pathways initiated in vivo that ultimately commit cardiac cells to apoptosis during ischemia/reperfusion. The goal of the present study was to determine whether mitochondrial-mediated mechanisms of apoptosis are initiated during in vivo cardiac ischemia/reperfusion. We provide evidence that the content of cytochrome c in the cytosol increases exclusively during reperfusion. Over the same time interval Bax, a pro-apoptotic protein implicated in release of cytochrome c from mitochondria, was found to disappear from cytosolic extracts. This was associated with the appearance of tightly associated Bax in the mitochondrial fraction. Cytochrome c from reperfused cytosolic extracts is present as a high molecular weight oligomer consistent with formation of the apoptosome. In addition, pro-caspase-9 was found to disappear exclusively during reperfusion. Therefore, the results of the current study indicate that the mitochondrial-mediated pathway of apoptosis is initiated as a result of in vivo cardiac ischemia/reperfusion.

AB - Reperfusion of myocardial tissue can result in programmed cell death. Nevertheless, relatively little information exists concerning pathways initiated in vivo that ultimately commit cardiac cells to apoptosis during ischemia/reperfusion. The goal of the present study was to determine whether mitochondrial-mediated mechanisms of apoptosis are initiated during in vivo cardiac ischemia/reperfusion. We provide evidence that the content of cytochrome c in the cytosol increases exclusively during reperfusion. Over the same time interval Bax, a pro-apoptotic protein implicated in release of cytochrome c from mitochondria, was found to disappear from cytosolic extracts. This was associated with the appearance of tightly associated Bax in the mitochondrial fraction. Cytochrome c from reperfused cytosolic extracts is present as a high molecular weight oligomer consistent with formation of the apoptosome. In addition, pro-caspase-9 was found to disappear exclusively during reperfusion. Therefore, the results of the current study indicate that the mitochondrial-mediated pathway of apoptosis is initiated as a result of in vivo cardiac ischemia/reperfusion.

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