Redox stress and the contributions of BH3-only proteins to infarction

Keith A Webster, Regina M Graham, John W. Thompson, Maria Grazia Spiga, Donna P. Frazier, Amber Wilson, Nanette Bishopric

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed death has been shown to be a significant component of infarction, and evidence indicates that multiple pathways are initiated during both ischemia and reperfusion phases. Major infarction is preceded by severe ischemia that includes hypoxia, intracellular acidosis, glucose depletion, loss of ATP, and elevation of cytoplasmic calcium. The superimposition of a reactive oxygen surge on the latter condition provides the impetus for maximal damage. Compelling evidence implicates mitochondria not only as the source of initiating ROS but also as the focal sensors that translate the redox stress signal into a cellular-death response. Pivotal to this response are the BH3-only proteins that are activated by death signals and regulate mitochondrial communication with executioner proteins in the cytoplasm. The BH3-only proteins do this by controlling the activity of pores and channels in the outer mitochondrial membrane. To date at least six BH3-only proteins have been shown to contribute to ischemia-reperfusion death pathways in heart and/or brain; these include Bnip3, PUMA, Bid, Bad, HGTD-P, and Noxa. Here we review the evidence for these cell-death pathways and discuss their relevance to ischemic disease and infarction.

Original languageEnglish
Pages (from-to)1667-1676
Number of pages10
JournalAntioxidants and Redox Signaling
Volume8
Issue number9-10
DOIs
StatePublished - Sep 1 2006

Fingerprint

Infarction
Oxidation-Reduction
Ischemia
Reperfusion
Mitochondria
Proteins
Noxae
Cell death
Mitochondrial Membranes
Reactive Oxygen Species
Brain
Electron Transport
Acidosis
Adenosine Triphosphate
Tissue
Oxygen
Calcium
Membranes
Cytoplasm
Glucose

ASJC Scopus subject areas

  • Biochemistry

Cite this

Webster, K. A., Graham, R. M., Thompson, J. W., Spiga, M. G., Frazier, D. P., Wilson, A., & Bishopric, N. (2006). Redox stress and the contributions of BH3-only proteins to infarction. Antioxidants and Redox Signaling, 8(9-10), 1667-1676. https://doi.org/10.1089/ars.2006.8.1667

Redox stress and the contributions of BH3-only proteins to infarction. / Webster, Keith A; Graham, Regina M; Thompson, John W.; Spiga, Maria Grazia; Frazier, Donna P.; Wilson, Amber; Bishopric, Nanette.

In: Antioxidants and Redox Signaling, Vol. 8, No. 9-10, 01.09.2006, p. 1667-1676.

Research output: Contribution to journalArticle

Webster, KA, Graham, RM, Thompson, JW, Spiga, MG, Frazier, DP, Wilson, A & Bishopric, N 2006, 'Redox stress and the contributions of BH3-only proteins to infarction', Antioxidants and Redox Signaling, vol. 8, no. 9-10, pp. 1667-1676. https://doi.org/10.1089/ars.2006.8.1667
Webster, Keith A ; Graham, Regina M ; Thompson, John W. ; Spiga, Maria Grazia ; Frazier, Donna P. ; Wilson, Amber ; Bishopric, Nanette. / Redox stress and the contributions of BH3-only proteins to infarction. In: Antioxidants and Redox Signaling. 2006 ; Vol. 8, No. 9-10. pp. 1667-1676.
@article{d0b0d826d0d545b2bf72185072988a56,
title = "Redox stress and the contributions of BH3-only proteins to infarction",
abstract = "Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed death has been shown to be a significant component of infarction, and evidence indicates that multiple pathways are initiated during both ischemia and reperfusion phases. Major infarction is preceded by severe ischemia that includes hypoxia, intracellular acidosis, glucose depletion, loss of ATP, and elevation of cytoplasmic calcium. The superimposition of a reactive oxygen surge on the latter condition provides the impetus for maximal damage. Compelling evidence implicates mitochondria not only as the source of initiating ROS but also as the focal sensors that translate the redox stress signal into a cellular-death response. Pivotal to this response are the BH3-only proteins that are activated by death signals and regulate mitochondrial communication with executioner proteins in the cytoplasm. The BH3-only proteins do this by controlling the activity of pores and channels in the outer mitochondrial membrane. To date at least six BH3-only proteins have been shown to contribute to ischemia-reperfusion death pathways in heart and/or brain; these include Bnip3, PUMA, Bid, Bad, HGTD-P, and Noxa. Here we review the evidence for these cell-death pathways and discuss their relevance to ischemic disease and infarction.",
author = "Webster, {Keith A} and Graham, {Regina M} and Thompson, {John W.} and Spiga, {Maria Grazia} and Frazier, {Donna P.} and Amber Wilson and Nanette Bishopric",
year = "2006",
month = "9",
day = "1",
doi = "10.1089/ars.2006.8.1667",
language = "English",
volume = "8",
pages = "1667--1676",
journal = "Antioxidants and Redox Signaling",
issn = "1523-0864",
publisher = "Mary Ann Liebert Inc.",
number = "9-10",

}

TY - JOUR

T1 - Redox stress and the contributions of BH3-only proteins to infarction

AU - Webster, Keith A

AU - Graham, Regina M

AU - Thompson, John W.

AU - Spiga, Maria Grazia

AU - Frazier, Donna P.

AU - Wilson, Amber

AU - Bishopric, Nanette

PY - 2006/9/1

Y1 - 2006/9/1

N2 - Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed death has been shown to be a significant component of infarction, and evidence indicates that multiple pathways are initiated during both ischemia and reperfusion phases. Major infarction is preceded by severe ischemia that includes hypoxia, intracellular acidosis, glucose depletion, loss of ATP, and elevation of cytoplasmic calcium. The superimposition of a reactive oxygen surge on the latter condition provides the impetus for maximal damage. Compelling evidence implicates mitochondria not only as the source of initiating ROS but also as the focal sensors that translate the redox stress signal into a cellular-death response. Pivotal to this response are the BH3-only proteins that are activated by death signals and regulate mitochondrial communication with executioner proteins in the cytoplasm. The BH3-only proteins do this by controlling the activity of pores and channels in the outer mitochondrial membrane. To date at least six BH3-only proteins have been shown to contribute to ischemia-reperfusion death pathways in heart and/or brain; these include Bnip3, PUMA, Bid, Bad, HGTD-P, and Noxa. Here we review the evidence for these cell-death pathways and discuss their relevance to ischemic disease and infarction.

AB - Ischemia followed by reperfusion is the primary cause of tissue injury and infarction during heart attack and stroke. The initiating stimulus is believed to involve reactive oxygen species that are produced during reperfusion when electron transport resumes in the mitochondria after suppression by ischemia. Programmed death has been shown to be a significant component of infarction, and evidence indicates that multiple pathways are initiated during both ischemia and reperfusion phases. Major infarction is preceded by severe ischemia that includes hypoxia, intracellular acidosis, glucose depletion, loss of ATP, and elevation of cytoplasmic calcium. The superimposition of a reactive oxygen surge on the latter condition provides the impetus for maximal damage. Compelling evidence implicates mitochondria not only as the source of initiating ROS but also as the focal sensors that translate the redox stress signal into a cellular-death response. Pivotal to this response are the BH3-only proteins that are activated by death signals and regulate mitochondrial communication with executioner proteins in the cytoplasm. The BH3-only proteins do this by controlling the activity of pores and channels in the outer mitochondrial membrane. To date at least six BH3-only proteins have been shown to contribute to ischemia-reperfusion death pathways in heart and/or brain; these include Bnip3, PUMA, Bid, Bad, HGTD-P, and Noxa. Here we review the evidence for these cell-death pathways and discuss their relevance to ischemic disease and infarction.

UR - http://www.scopus.com/inward/record.url?scp=33750901803&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=33750901803&partnerID=8YFLogxK

U2 - 10.1089/ars.2006.8.1667

DO - 10.1089/ars.2006.8.1667

M3 - Article

VL - 8

SP - 1667

EP - 1676

JO - Antioxidants and Redox Signaling

JF - Antioxidants and Redox Signaling

SN - 1523-0864

IS - 9-10

ER -