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Extracellular ATP as a trigger for apoptosis or programmed cell death
Journal of Cell Biology
  • Li-Mou Zheng, The Rockefeller University
  • Arturo Zychlinsky, The Rockefeller University
  • Chau-Ching Liu, The Rockefeller University
  • David M. Ojcius, The Rockefeller University
  • John Ding-E. Young, The Rockefeller University
David M. Ojcius: 0000-0003-1461-4495
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Extracellular ATP is shown here to induce programmed cell death (or apoptosis) in thymocytes and certain tumor cell lines. EM studies indicate that the ATP-induced death of thymocytes and susceptible tumor cells follows morphological changes usually associated with glucocorticoid-induced apoptosis of thymocytes. These changes include condensation of chromatin, blebbing of the cell surface, and breakdown of the nucleus. Cytotoxicity assays using double-labeled cells show that ATP-mediated cell lysis is accompanied by fragmentation of the target cell DNA. DNA fragmentation can be set off by ATP but not the nonhydrolysable analogue ATP gamma S nor other nucleoside-5'-triphosphates. ATP-induced DNA fragmentation but not ATP-induced 51Cr release can be blocked in cells pretreated with inhibitors of protein or RNA synthesis or the endonuclease inhibitor, zinc; whereas pretreatment with calmidazolium, a potent calmodulin antagonist, blocks both DNA fragmentation and 51Cr release. The biochemical and morphological changes caused by ATP are preceded by a rapid increase in the cytoplasmic calcium of the susceptible cell. Calcium fluxes by themselves, however, are not sufficient to cause apoptosis, as the pore-forming protein, perforin, causes cell lysis without DNA fragmentation or the morphological changes associated with apoptosis. Taken together, these results indicate that ATP can cause cell death through two independent mechanisms, one of which, requiring an active participation on the part of the cell, takes place through apoptosis.
Citation Information
Li-Mou Zheng, Arturo Zychlinsky, Chau-Ching Liu, David M. Ojcius, et al.. "Extracellular ATP as a trigger for apoptosis or programmed cell death" Journal of Cell Biology Vol. 112 Iss. 2 (1991) p. 279 - 288 ISSN: 0021-9525
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