Mechanisms of cell death in hypoxia/reoxygenation injury

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

Research output: Contribution to journalArticle

218 Citations (Scopus)

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
StatePublished - Jan 1 1998

Fingerprint

Cell Death
Wounds and Injuries
Apoptosis Regulatory Proteins
Caspase Inhibitors
Caspases
Inflammation
DNA Cleavage
Electron Transport
Cytochromes c
Artifacts
Reperfusion
Hypoxia
Cause of Death
Cultured Cells
Permeability
Mitochondria
Respiration
Anti-Inflammatory Agents
Necrosis
Ischemia

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

Mechanisms of cell death in hypoxia/reoxygenation injury. / Saikumar, Pothana; Dong, Zheng; Weinberg, Joel M.; Venkatachalam, M. A.

In: Oncogene, Vol. 17, No. 25, 01.01.1998, p. 3341-3349.

Research output: Contribution to journalArticle

Saikumar, P, Dong, Z, Weinberg, JM & Venkatachalam, MA 1998, 'Mechanisms of cell death in hypoxia/reoxygenation injury', Oncogene, vol. 17, no. 25, pp. 3341-3349. https://doi.org/10.1038/sj.onc.1202579
Saikumar P, Dong Z, Weinberg JM, Venkatachalam MA. Mechanisms of cell death in hypoxia/reoxygenation injury. Oncogene. 1998 Jan 1;17(25):3341-3349. https://doi.org/10.1038/sj.onc.1202579
Saikumar, Pothana ; Dong, Zheng ; Weinberg, Joel M. ; Venkatachalam, M. A. / Mechanisms of cell death in hypoxia/reoxygenation injury. In: Oncogene. 1998 ; Vol. 17, No. 25. pp. 3341-3349.
@article{90b2240419904776b5ba49487dfae336,
title = "Mechanisms of cell death in hypoxia/reoxygenation injury",
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.",
keywords = "Apoptosis, Bax, Bcl-7, Hypoxia, Necrosis, Reoxygenation",
author = "Pothana Saikumar and Zheng Dong and Weinberg, {Joel M.} and Venkatachalam, {M. A.}",
year = "1998",
month = "1",
day = "1",
doi = "10.1038/sj.onc.1202579",
language = "English (US)",
volume = "17",
pages = "3341--3349",
journal = "Oncogene",
issn = "0950-9232",
publisher = "Nature Publishing Group",
number = "25",

}

TY - JOUR

T1 - Mechanisms of cell death in hypoxia/reoxygenation injury

AU - Saikumar, Pothana

AU - Dong, Zheng

AU - Weinberg, Joel M.

AU - Venkatachalam, M. A.

PY - 1998/1/1

Y1 - 1998/1/1

N2 - 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.

AB - 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.

KW - Apoptosis

KW - Bax

KW - Bcl-7

KW - Hypoxia

KW - Necrosis

KW - Reoxygenation

UR - http://www.scopus.com/inward/record.url?scp=0032409943&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032409943&partnerID=8YFLogxK

U2 - 10.1038/sj.onc.1202579

DO - 10.1038/sj.onc.1202579

M3 - Article

C2 - 9916996

AN - SCOPUS:0032409943

VL - 17

SP - 3341

EP - 3349

JO - Oncogene

JF - Oncogene

SN - 0950-9232

IS - 25

ER -