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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Brehm, Reina Naval, Javier Wallich, Reinhard Müllbacher, Arno Anel, Alberto Bosque, Alberto Pardo, Julián Simon, Markus M. |
| Description | Author Affiliation: Pardo J ( Departmento de Bioquímica y Biología Molecular y Celular, Universidad de Zaragoza, E-50009 Zaragoza, Spain.) |
| Abstract | Purified cytolytic T lymphocyte (CTL) proteases granzyme (gzm)A and gzmB with sublytic dose of perforin (perf) initiate distinct proapoptotic pathways. Their physiological relevance in CTL-mediated target cell apoptosis is elusive. Using ex vivo virus-immune $CD8^{+}$ T cells from mice deficient in perf, gzmA and/or gzmB, and the Fas-resistant EL4.F15 tumor target cell, we show that (a) CTL from $gzmA^{−/−}$ or $gzmB^{−/−}$ mice similarly induced early proapoptotic features, such as phosphatidyl serine (PS) exposure on plasma membrane, $ΔΨ_{m}$ loss, and reactive oxygen radical generation, though with distinct kinetics; (b) CTL from $gzmA^{−/−}$ but not from $gzmB^{−/−}$ mice activate caspase 3 and 9; (c) PS exposure induced by CTL from $gzmA^{−/−}$ or $gzmB^{−/−}$ mice is prevented, respectively, by caspase inhibitors or by reactive oxygen scavengers without interfering with target cell death; and (d) all gzm-induced apoptotic features analyzed depend critically on perf. Thus, perf is the principal regulator in CTL-mediated and gzm-facilitated intracellular processes. The ability of gzmA and gzmB to induce multiple independent cell death pathways may be the hosts response to circumvent evasion strategies of pathogens and tumors. |
| ISSN | 00219525 |
| e-ISSN | 15408140 |
| Journal | The Journal of Cell Biology |
| Issue Number | 3 |
| Volume Number | 167 |
| Language | English |
| Publisher | Rockefeller University Press (United States) |
| Publisher Date | 2004-11-08 |
| Publisher Place | United States |
| Access Restriction | Open |
| Subject Keyword | Apoptosis Immunology Cytotoxicity, Immunologic Serine Endopeptidases Physiology T-Lymphocytes, Cytotoxic Enzymology Animals Cell Line, Tumor Cells, Cultured Granzymes Kinetics Membrane Glycoproteins Membrane Potentials Mice Mice, Knockout Perforin Phosphatidylserines Metabolism Pore Forming Cytotoxic Proteins Reactive Oxygen Species Deficiency Time Factors Research Support, Non-U.S. Gov't Cell Biology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Cell Biology Medicine |
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