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© The Rockefeller University Press, 0021-9525/2003/12/1185 $8.00
The Journal of Cell Biology, Volume 163, Number 6, 1185-1185

Death and the shrinking nucleus

PLA2 (right) shrinks nuclei during hypoxic death.

During heart disease and stroke, cells deprived of oxygen often die in a way that is distinct from caspase-dependent apoptosis. On page 1219, Shinzawa and Tsujimoto provide a first look at the molecular basis of this poorly understood process, showing that a phospholipase A₂ (PLA₂) enzyme causes the characteristic nuclear shrinkage that accompanies hypoxic cell death.

Using a novel permeabilized cell assay, the authors purified a protein that can cause nuclear shrinkage and identified it as PLA₂. Inhibitor studies confirmed that PLA₂ is essential for nuclear shrinkage in caspase-independent hypoxic cell death. In hypoxic cells, PLA₂ activity increases and the calcium-independent form of the enzyme accumulates in the nucleus. Blocking calcium-independent PLA₂ activity prevents both nuclear shrinkage and hypoxic cell death.

An increase in PLA₂ activity leads to the cleavage of nuclear lamins, which could explain how it causes nuclear shrinkage. Since PLA₂ cleaves phospholipids, it could also contribute to cell death by disrupting mitochondrial and plasma membranes, processes the authors now hope to study biochemically. The identification of PLA₂ as an important mediator of caspase-independent death should also help uncover additional components of the pathway, such as the regulators of PLA₂ activity and translocation.

Alan W. Dove

alanwdove{at}earthlink.net

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PLA₂ activity is required for nuclear shrinkage in caspase-independent cell death

Koei Shinzawa and Yoshihide Tsujimoto
J. Cell Biol. 2003 163: 1219-1230. [Abstract] [Full Text] [PDF]

This Article Full Text (PDF, 470K) PPT slides of all figures Alert me when this article is cited Services Email this article Similar articles in this journal Alert me to new content in the JCB Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Dove, A. W. Search for Related Content PubMed Articles by Dove, A. W. Related Collections Related Article Social Bookmarking                            What's this?