title: A distinct pathway of cell-mediated apoptosis initiated by granulysin.
abstract: Granulysin is an antimicrobial and tumoricidal molecule expressed in granules of CTL and NK cells. In this study, we show that granulysin damages cell membranes based upon negative charge, disrupts the transmembrane potential (Deltapsi) in mitochondria, and causes release of cytochrome c. Granulysin-induced apoptosis is blocked in cells overexpressing Bcl-2. Despite the release of cytochrome c, procaspase 9 is not processed. Nevertheless, activation of caspase 3 is observed in granulysin-treated cells, suggesting that granulysin activates a novel pathway of CTL- and NK cell-mediated death distinct from granzyme- and death receptor-induced apoptosis.
authors: Division of Immunology and Transplantation Biology, Department of Pediatrics, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors: A A
authors: AA
authors: Kaspar
authors: S
authors: S
authors: Okada
authors: J
authors: J
authors: Kumar
authors: F R
authors: FR
authors: Poulain
authors: K A
authors: KA
authors: Drouvalakis
authors: A
authors: A
authors: Kelekar
authors: D A
authors: DA
authors: Hanson
authors: R M
authors: RM
authors: Kluck
authors: Y
authors: Y
authors: Hitoshi
authors: D E
authors: DE
authors: Johnson
authors: C J
authors: CJ
authors: Froelich
authors: C B
authors: CB
authors: Thompson
authors: D D
authors: DD
authors: Newmeyer
authors: A
authors: A
authors: Anel
authors: C
authors: C
authors: Clayberger
authors: A M
authors: AM
authors: Krensky
mesh_terms: D000945:Antigens, Differentiation, T-Lymphocyte / Q000502:physiology* / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects / Q000276:immunology*; D003574:Cytochrome c Group / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D006801:Humans; D007425:Intracellular Membranes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D008563:Membrane Lipids / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects / Q000276:immunology; D008928:Mitochondria / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000276:immunology*; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
chemical_list: D000945:Antigens, Differentiation, T-Lymphocyte; D003574:Cytochrome c Group; C075005:GNLY protein, human; D008563:Membrane Lipids