Mechanisms of cell death in hypoxia/reoxygenation injury

Pothana Saikumar, Zheng Dong, Joel M. Weinberg, M. A. Venkatachalam

Research output: Contribution to journalArticle

221 Scopus citations

Abstract

Investigation of death pathways during cell injury in vivo caused by ischemia and reperfusion is of clinical importance, but technically difficult. Heterogeneity of cell types, differences between organ systems, diversity of death paradigms and exacerbation of tissue damage caused by inflammation are only some of the variables that need to be taken into account. With respect to the identification of necrosis and apoptosis in affected organs, technical issues related to preparation artifacts, occurrence of internucleosomal DNA cleavage in necrotic as well as apoptotic cells and other overlaps in death pathways bear consideration. In that caspase independent as well as caspase dependent processes cause cell death and that caspase inhibitors can act as anti-inflammatory agents, evaluation of ischemic death mechanisms in parenchymal cells needs to be performed with caution. When the effects of inflammation are removed by appropriate in vitro studies using purified or cultured cells, several mitochondrial factors that lead to cell death can be studied. Substantial evidence exists for the participation of electron transport defects, mitochondrial permeability transitions (MPT) and release of cytochrome c from mitochondria, effected by pro-apoptotic proteins such as Bax. The anti-apoptotic protein Bcl-2 exerts an overriding protective role in this type of injury by preserving mitochondrial structure and function. In contrast, caspase inhibitors cannot offer long-term protection to ischemically injured parenchymal cells regardless of how effectively they can inhibit apoptotic events, if the cells have suffered permanent mitochondrial damage impairing respiration.

Original languageEnglish (US)
Pages (from-to)3341-3349
Number of pages9
JournalOncogene
Volume17
Issue number25
DOIs
Publication statusPublished - Jan 1 1998
Externally publishedYes

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Keywords

  • Apoptosis
  • Bax
  • Bcl-7
  • Hypoxia
  • Necrosis
  • Reoxygenation

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cancer Research

Cite this

Saikumar, P., Dong, Z., Weinberg, J. M., & Venkatachalam, M. A. (1998). Mechanisms of cell death in hypoxia/reoxygenation injury. Oncogene, 17(25), 3341-3349. https://doi.org/10.1038/sj.onc.1202579