Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress

David J. McConkey; Pia Hartzell; Pierluigi Nicotera; Andrew H. Wyllie; Sten Orrenius

doi:10.1016/0378-4274(88)90069-0

Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress

David J. McConkey, Pia Hartzell, Pierluigi Nicotera, Andrew H. Wyllie, Sten Orrenius

Research output: Contribution to journal › Article › peer-review

152 Scopus citations

Abstract

Incubation of freshly isolated rat hepatocytes with moderately toxic concentrations of menadione [2-methyl-1,4-naphthoquinone) resulted in chromatin condensation and progressive DNA fragmentation, suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in programmed cell death (apoptosis). Endonuclease activation followed upon a sustained increase in cytosolic Ca²⁺ concentration and preceded cell killing by 1-2 h. It is concluded that generation of oxidative stress in hepatocytes can activate processes similar to those observed during programmed cell death.

Original language	English (US)
Pages (from-to)	123-130
Number of pages	8
Journal	Toxicology Letters
Volume	42
Issue number	2
DOIs	https://doi.org/10.1016/0378-4274(88)90069-0
State	Published - Aug 1988
Externally published	Yes

Keywords

Calcium
DNA fragmentation
Isolated hepatocytes
Menadione

ASJC Scopus subject areas

Toxicology

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10.1016/0378-4274(88)90069-0

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title = "Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress",

abstract = "Incubation of freshly isolated rat hepatocytes with moderately toxic concentrations of menadione [2-methyl-1,4-naphthoquinone) resulted in chromatin condensation and progressive DNA fragmentation, suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in programmed cell death (apoptosis). Endonuclease activation followed upon a sustained increase in cytosolic Ca2+ concentration and preceded cell killing by 1-2 h. It is concluded that generation of oxidative stress in hepatocytes can activate processes similar to those observed during programmed cell death.",

keywords = "Calcium, DNA fragmentation, Isolated hepatocytes, Menadione",

author = "McConkey, {David J.} and Pia Hartzell and Pierluigi Nicotera and Wyllie, {Andrew H.} and Sten Orrenius",

note = "Funding Information: This study was supportedb y grantsf rom the SwedishM edical ResearchC ouncil (Proj. No. 03X-2471)a nd the SwedishC ouncil for the Planning and Coordination of Researcha nd by a fellowship from the American-ScandinavianF oundation (D.J.M.).",

year = "1988",

month = aug,

doi = "10.1016/0378-4274(88)90069-0",

language = "English (US)",

volume = "42",

pages = "123--130",

journal = "Toxicology Letters",

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TY - JOUR

T1 - Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress

AU - McConkey, David J.

AU - Hartzell, Pia

AU - Nicotera, Pierluigi

AU - Wyllie, Andrew H.

AU - Orrenius, Sten

N1 - Funding Information: This study was supportedb y grantsf rom the SwedishM edical ResearchC ouncil (Proj. No. 03X-2471)a nd the SwedishC ouncil for the Planning and Coordination of Researcha nd by a fellowship from the American-ScandinavianF oundation (D.J.M.).

PY - 1988/8

Y1 - 1988/8

N2 - Incubation of freshly isolated rat hepatocytes with moderately toxic concentrations of menadione [2-methyl-1,4-naphthoquinone) resulted in chromatin condensation and progressive DNA fragmentation, suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in programmed cell death (apoptosis). Endonuclease activation followed upon a sustained increase in cytosolic Ca2+ concentration and preceded cell killing by 1-2 h. It is concluded that generation of oxidative stress in hepatocytes can activate processes similar to those observed during programmed cell death.

AB - Incubation of freshly isolated rat hepatocytes with moderately toxic concentrations of menadione [2-methyl-1,4-naphthoquinone) resulted in chromatin condensation and progressive DNA fragmentation, suggestive of the stimulation of an endogenous endonuclease activity previously found to be involved in programmed cell death (apoptosis). Endonuclease activation followed upon a sustained increase in cytosolic Ca2+ concentration and preceded cell killing by 1-2 h. It is concluded that generation of oxidative stress in hepatocytes can activate processes similar to those observed during programmed cell death.

KW - Calcium

KW - DNA fragmentation

KW - Isolated hepatocytes

KW - Menadione

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DO - 10.1016/0378-4274(88)90069-0

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JO - Toxicology Letters

JF - Toxicology Letters

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ER -

Stimulation of endogenous endonuclease activity in hepatocytes exposed to oxidative stress

Abstract

Keywords

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