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Differential regula...
Differential regulation and ATP requirement for caspase-8 and caspase-3 activation during CD95- and anticancer drug-induced apoptosis
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- Ferrari, D. (författare)
- Department of Internal Medicine I, Eberhard-Karls University, D-72076 Tübingen, Germany
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- Stepczynska, A. (författare)
- Department of Internal Medicine I, Eberhard-Karls University, D-72076 Tübingen, Germany
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- Los, Marek Jan (författare)
- Department of Internal Medicine I, Eberhard-Karls University, D-72076 Tübingen, Germany
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- Wesselborg, Sebastian (författare)
- Department of Internal Medicine I, Eberhard-Karls University, D-72076 Tübingen, Germany
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- Schulze-Osthoff, Klaus (författare)
- Department of Internal Medicine I, Eberhard-Karls University, D-72076 Tübingen, Germany
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(creator_code:org_t)
- 1998-09-07
- 1998
- Engelska.
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Ingår i: Journal of Experimental Medicine. - : Rockefeller University Press. - 0022-1007 .- 1540-9538. ; 188:5, s. 979-984
- Relaterad länk:
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https://liu.diva-por... (primary) (Raw object)
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http://jem.rupress.o...
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Apoptosis is induced by different stimuli, among them triggering of the death receptor CD95, staurosporine, and chemotherapeutic drugs. In all cases, apoptosis is mediated by caspases, although it is unclear how these diverse apoptotic stimuli cause protease activation. Two regulatory pathways have been recently identified, but it remains unknown whether they are functionally independent or linked to each other. One is mediated by recruitment of the proximal regulator caspase-8 to the death receptor complex. The other pathway is controlled by the release of cytochrome c from mitochondria and the subsequent ATP-dependent activation of the death regulator apoptotic protease-activating factor 1 (Apaf-1). Here, we report that both pathways can be dissected by depletion of intracellular ATP. Prevention of ATP production completely inhibited caspase activation and apoptosis in response to chemotherapeutic drugs and staurosporine. Interestingly, caspase-8, whose function appeared to be restricted to death receptors, was also activated by these drugs under normal conditions, but not after ATP depletion. In contrast, inhibition of ATP production did not affect caspase activation after triggering of CD95. These results suggest that chemotherapeutic drug-induced caspase activation is entirely controlled by a receptor-independent mitochondrial pathway, whereas CD95-induced apoptosis can be regulated by a separate pathway not requiring Apaf-1 function.
Ämnesord
- NATURVETENSKAP -- Biologi -- Biokemi och molekylärbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Biochemistry and Molecular Biology (hsv//eng)
- NATURVETENSKAP -- Biologi -- Cellbiologi (hsv//swe)
- NATURAL SCIENCES -- Biological Sciences -- Cell Biology (hsv//eng)
Nyckelord
- anticancer drugs
- apo-1/fas receptor/ligand system
- Apoptosis
- atp
- Bcl-2
- CD95 (APO-1/Fas)
- cell-death
- crma-inhibitable protease
- cytochrome c
- cytochrome-c
- fas-mediated apoptosis
- flice
- Mitochondria
- signaling complex disc
- wild-type
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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