J.Jpn. Surg. Soc.. 100(10): 656-662, 1999

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Feature topic

MECHANISMS OF CELL DEATH IN HYPOXIC STRESS

The present article attempts to summarize and introduce the mechanisms of hypoxia-induced cell death. Necrosis is associated with rapid metabolic collapse that leads to cell swelling, early loss of plasma membrane integrity, and ultimate cell rupture, in which cytosolic contents leak from necrotic cells causing injury to and inflammation of the surrounding tissue. In contrast, apoptosis is an energy-requiring, gene-directed process, which results in cell suicide without any injury to surrounding tissues. Although apoptosis and necrosis are conceptually distinct pathways of cell death, recent advances have revealed that hypoxic cell damage can induce both necrosis and apoptosis simultaneously. Loss of the mitochondrial membrane potential (MMP) precedes the morphological changes in cell death, and overexpression of Bcl-2 or Bcl-XL blocks apoptosis as well as hypoxia-induced necrosis by maintaining MMP. These findings indicate that apoptosis and some types of necrosis share common features in the death signaling pathway. The factors that determine whether cells undergo apoptosis or necrosis are still unclear, but intracellular ATP levels and/or their rate of decline are considered to be one possible determinant of the manifestation of cell death.

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