Gerald M. Cohen

MRC Toxicology Unit

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David Dinsdale

University of Leicester

M.G. Ormerod

Institute of Cancer Research

Howard O. Fearnhead

Ollscoil na Gaillimhe – University of Galway

Roger T. Snowden

Medical Research Council

Xiaoming Sun

Shanghai Jiao Tong University

Maciej Chwalinski

MRC Toxicology Unit

Jianguo Zhuang

University of Liverpool

Cooperative Institutions

MRC Toxicology Unit

University of Leicester

Medical Research Council

Leicester City Council

Shanghai Jiao Tong University

Shanghai Ninth People's Hospital

Jilin Business and Technology College

Jilin Province Science and Technology Department

Harbin University of Science and Technology

Shanghai Institute of Pollution Control and Ecological Security

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An interleukin‐1β‐converting enzyme‐like protease is a common mediator of apoptosis in thymocytes

FEBS Letters (1995)

Howard O. Fearnhead David Dinsdale Gerald M. Cohen

Apoptosis was induced in thymocytes using diverse stimuli in order to identify events within a common apoptotic pathway. Benzyloxycarbonyl‐valinyl‐alaninyl‐aspartyl fluoromethyl ketone (Z‐VAD.FMK), an interleukin‐1β‐converting enzyme (ICE)‐like protease inhibitor, inhibited apoptosis assessed by flow cytometry, proteolysis of poly (ADP)‐ribose polymerase (PARP), an early biochemical marker of apoptosis, and cleavage of DNA to both large kilobase pair fragments.(30–50 and 200–300 kbp) and to nucleosomal fragments. Z‐VAD.FMK also blocked all the classical ultrastructural features of apoptosis including chromatin condensation to one pole of the nucleus, nucleolar disintegration and cytoplasmic vacuolation. These results suggest the involvement of an ICE‐like protease as a common mediator of apoptosis in thymocytes.

Proteolysis

10.1016/0014-5793(95)01228-7

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Citations (102)

Redistribution of Cytochrome c Precedes the Caspase-Dependent Formation of Ultracondensed Mitochondria, with a Reduced Inner Membrane Potential, in Apoptotic Monocytes

American Journal Of Pathology (1999)

David Dinsdale Jianguo Zhuang Gerald M. Cohen

Mitochondrial apoptosis-induced channel

Apoptosome

Inner membrane

10.1016/s0002-9440(10)65156-5

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Critical Changes In Apoptosis In Thymocytes Precede Endonuclease Activation

CRC Press eBooks (2024)

Gerald M. Cohen Xiaoming Sun Roger T. Snowden M.G. Ormerod David Dinsdale

Apoptosis is a major form of cell death occurring in a wide variety of different biological systems including normal cell turnover, embryonic and T-cell development, metamorphosis, hormone-dependent atrophy, immune and toxic cell killing (Arends and Wyllie, 1991; Ellis et al., 1991 ; Cohen et al., 1992b). It is an active form of selfdestruction, which is characterized by condensation and fragmentation of nuclear chromatin, accompanied by compaction of cellular organelles, dilatation of the endoplasmic reticulum and a marked reduction in cell volume (Wyllie et al., 1980,- Arends and Wyllie, 1991). Volume reduction is such a prominent feature of apoptosis that initially this type of cell death was known as shrinkage necrosis (Kerr, 1971). The morphological changes of apoptosis have been associated with endonuclease cleavage of DNA into nucleosomal length fragments of 180-200 base pairs or multiples thereof (Wyllie, 1980). Here we report that key morphological changes of apoptosis in thymocytes, precede and can be dissociated experimentally from DNA fragmentation produced as a result of endonuclease activity. Thus internucleosomal cleavage of DNA is a late event in apoptosis.

10.1201/9781003580539-12

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Dexamethasone and etoposide induce apoptosis in rat thymocytes from different phases of the cell cycle

Biochemical Pharmacology (1994)

Howard O. Fearnhead Maciej Chwalinski Roger T. Snowden M.G. Ormerod Gerald M. Cohen

Thymocyte

10.1016/0006-2952(94)90142-2

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Citations (23)