Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c

Li, Feng; Srinivasan, Anu; Wang, Yu; Armstrong, Robert C.; Tomaselli, Kevin J.; Fritz, Lawrence C.

doi:10.1074/jbc.272.48.30299

Cited by 323 publications

(155 citation statements)

References 34 publications

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“…The resultant cleavage and activation of caspase 9 leads, in turn, to the activation of downstream executioner caspases (e.g., caspase 3) that cause DNA damage, disruption of cytoskeletal proteins and the stereotypical changes that characterize apoptotic cell death. 33 In the present study, every cell injected with cyC (n ¼ 450) initially showed signs of cell death within a short period (o30 min), while 1-2 h were required for complete degeneration following the injection.…”

Section: Cytochrome C-induced Cell Deathmentioning

confidence: 56%

“…The use of cyC to induce cell death is now a relatively common procedure, [4][5][6]19,20,33 and provides a convenient means to circumvent the need for various extracellular signaling molecules that activate membrane receptors of the death domain family. Cytoplasmic cyC is an important component of the apoptotic cascade, and its release from mitochondria precedes exposure of phosphatidylserine, the loss of plasma membrane integrity, and other indices of apoptosis.…”

Section: Cytochrome C-induced Cell Deathmentioning

confidence: 99%

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Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to ‘bystander’ cell killing

et al. 2006

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Previous reports have shown that gap junctions relay cell death in many cell types. However, changes in electrical coupling and their dynamics during cell death are poorly understood. We performed comprehensive studies of electrical coupling following induction of cell death by single-cell cytochrome c (cyC) injection in paired Xenopus oocytes. Cell death was rapidly induced by cyC in injected cells, and cell death was also observed in uninjected bystander cells electrically coupled to the cyC-injected oocytes. Gap junction currents either remained at pre-cyC injection levels or increased dramatically as the injected cell died. Nonjunctional currents increased in injected cells immediately following cyC injection; nonjunctional currents increased slowly in uninjected bystander cells. Bystander cell death occurred only when junctional conductance was B6 lS. Both 1,2-bis-(o-aminophenoxy)-ethane-N,N,-N 0 ,N 0 -tetraacetic acid tetraacetoxy-methyl ester and Xestospongin C inhibited bystander cell death in pairs that had reached the death conductance threshold, suggesting that Ca 2 þ and inositol 1,4,5 triphosphate are involved in the process.

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Section: Cytochrome C-induced Cell Deathmentioning

confidence: 56%

Section: Cytochrome C-induced Cell Deathmentioning

confidence: 99%

Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to ‘bystander’ cell killing

et al. 2006

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“…In order to determine the exact location of caspase-8 in the mitochondrial pathway, we used the human breast carcinoma cell line MCF7. Recently it has been demonstrated that MCF7 cells are de®cient in caspase-3 expression (JaÈ nicke et al, 1998) and this may account for the inability of micro-injected cytochrome c to induce apoptosis in these cells (Li et al, 1997a). Therefore, we reasoned that if caspase-8 is activated by caspase-3 downstream of caspase-9, it should not be activated by anticancer drugs.…”

Section: Caspase-8 Is Not Required For Anticancer Drug-mediated Apoptmentioning

confidence: 96%

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

et al. 2000

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Caspase-8 plays an essential role in apoptosis triggered by death receptors. Through the cleavage of Bid, a proapoptotic Bcl-2 member, it further activates the mitochondrial cytochrome c/Apaf-1 pathway. Because caspase-8 can be processed also by anticancer drugs independently of death receptors, we investigated its exact role and order in the caspase cascade. We show that in Jurkat cells either de®cient for caspase-8 or overexpressing its inhibitor c-FLIP apoptosis mediated by CD95, but not by anticancer drugs was inhibited. In the absence of active caspase-8, anticancer drugs still induced the processing of caspase-9, -3 and Bid, indicating that Bid cleavage does not require caspase-8. Overexpression of Bcl-x L prevented the processing of caspase-8 as well as caspase-9, -6 and Bid in response to drugs, but was less e ective in CD95-induced apoptosis. Similar responses were observed by overexpression of a dominant-negative caspase-9 mutant. To further determine the order of caspase-8 activation, we employed MCF7 cells lacking caspase-3. In contrast to caspase-9 that was cleaved in these cells, anticancer drugs induced caspase-8 activation only in caspase-3 transfected MCF7 cells. Thus, our data indicate that, unlike its proximal role in receptor signaling, in the mitochondrial pathway caspase-8 rather functions as an amplifying executioner caspase.

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“…27,28,30 ± 32 Microinjected cytochrome c causes apoptosis of HeLa carcinoma and embryonic kidney 293 cells, but not of caspase-3-defective MCF-7 cells. 33 Transformation of MCF-7 cells with CASP-3 cDNA restores cytochrome c sensitivity, demonstrating that cytochrome c-mediated apoptosis requires caspase-3. 33 There is evidence that caspase-3 activation can also occur independently of mitochondrial cytochrome c release.…”

Section: The Cytochrome C ± Caspase-3 Connectionmentioning

confidence: 99%

Emerging roles of caspase-3 in apoptosis

1999

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Caspases are crucial mediators of programmed cell death (apoptosis). Among them, caspase-3 is a frequently activated death protease, catalyzing the specific cleavage of many key cellular proteins. However, the specific requirements of this (or any other) caspase in apoptosis have remained largely unknown until now. Pathways to caspase-3 activation have been identified that are either dependent on or independent of mitochondrial cytochrome c release and caspase-9 function. Caspase-3 is essential for normal brain development and is important or essential in other apoptotic scenarios in a remarkable tissue-, cell type-or death stimulus-specific manner. Caspase-3 is also required for some typical hallmarks of apoptosis, and is indispensable for apoptotic chromatin condensation and DNA fragmentation in all cell types examined. Thus, caspase-3 is essential for certain processes associated with the dismantling of the cell and the formation of apoptotic bodies, but it may also function before or at the stage when commitment to loss of cell viability is made.

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Cell-specific Induction of Apoptosis by Microinjection of Cytochrome c

Cited by 323 publications

References 34 publications

Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to ‘bystander’ cell killing

Gap junctions remain open during cytochrome c-induced cell death: relationship of conductance to ‘bystander’ cell killing

Caspase-8/FLICE functions as an executioner caspase in anticancer drug-induced apoptosis

Emerging roles of caspase-3 in apoptosis

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