Programmed cell death in mature erythrocytes: a model for investigating death effector pathways operating in the absence of mitochondria View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2001-12

AUTHORS

D Bratosin, J Estaquier, F Petit, D Arnoult, B Quatannens, J-P Tissier, C Slomianny, C Sartiaux, C Alonso, J-J Huart, J Montreuil, J C Ameisen

ABSTRACT

Human mature erythrocytes have been considered as unable to undergo programmed cell death (PCD), due to their lack of mitochondria, nucleus and other organelles, and to the finding that they survive two conditions that induce PCD in vitro in all human nucleated cells, treatment with staurosporine and serum deprivation. Here we report that mature erythrocytes can undergo a rapid self-destruction process sharing several features with apoptosis, including cell shrinkage, plasma membrane microvesiculation, phosphatidylserine externalization, and leading to erythrocyte disintegration, or, in the presence of macrophages, to macrophage ingestion of dying erythrocytes. This regulated form of PCD was induced by Ca(2+) influx, and prevented by cysteine protease inhibitors that allowed erythrocyte survival in vitro and in vivo. The cysteine proteinases involved seem not to be caspases, since (i) proforms of caspase 3, while present in erythrocytes, were not activated during erythrocyte death; (ii) cytochrome c, a critical component of the apoptosome, was lacking; and (iii) cell-free assays did not detect activated effectors of nuclear apoptosis in dying erythrocytes. Our findings provide the first identification that a death program can operate in the absence of mitochondria. They indicate that mature erythrocytes share with all other mammalian cell types the capacity to self-destruct in response to environmental signals, and imply that erythrocyte survival may be modulated by therapeutic intervention. More... »

PAGES

4400946

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/sj.cdd.4400946

DOI

http://dx.doi.org/10.1038/sj.cdd.4400946

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1010213587

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/11753563


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