Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury

Elizabeth Murphy, Charles Jr Steenbergen

Research output: Contribution to journalArticle

Abstract

Mitochondria play an important role in cell death and cardioprotection. During ischemia, when ATP is progressively depleted, ion pumps cannot function resulting in a rise in calcium (Ca2+), which further accelerates ATP depletion. The rise in Ca2+ during ischemia and reperfusion leads to mitochondrial Ca2+ accumulation, particularly during reperfusion when oxygen is reintroduced. Reintroduction of oxygen allows generation of ATP; however, damage to the electron transport chain results in increased mitochondrial generation of reactive oxygen species (ROS). Mitochondrial Ca 2+ overload and increased ROS can result in opening of the mitochondrial permeability transition pore, which further compromises cellular energetics. The resultant low ATP and altered ion homeostasis result in rupture of the plasma membrane and cell death. Mitochondria have long been proposed as central players in cell death, since the mitochondria are central to synthesis of both ATP and ROS and since mitochondrial and cytosolic Ca2+ overload are key components of cell death. Many cardioprotective mechanisms converge on the mitochondria to reduce cell death. Reducing Ca2+ overload and reducing ROS have both been reported to reduce ischemic injury. Preconditioning activates a number of signaling pathways that reduce Ca 2+ overload and reduce activation of the mitochondrial permeability transition pore. The mitochondrial targets of cardioprotective signals are discussed in detail.

Original languageEnglish (US)
Pages (from-to)581-609
Number of pages29
JournalPhysiological Reviews
Volume88
Issue number2
DOIs
StatePublished - Apr 2008
Externally publishedYes

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Reperfusion Injury
Cell Death
Adenosine Triphosphate
Reactive Oxygen Species
Mitochondria
Reperfusion
Ischemia
Ion Pumps
Oxygen
Electron Transport
Plasma Cells
Rupture
Homeostasis
Cell Membrane
Ions
Calcium
Wounds and Injuries
mitochondrial permeability transition pore

ASJC Scopus subject areas

  • Physiology

Cite this

Mechanisms underlying acute protection from cardiac ischemia-reperfusion injury. / Murphy, Elizabeth; Steenbergen, Charles Jr.

In: Physiological Reviews, Vol. 88, No. 2, 04.2008, p. 581-609.

Research output: Contribution to journalArticle

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