Direct Observation of Release of Cytochrome c from Lipid-Encapsulated Protein by Peroxide and Superoxide: A Possible Mechanism for Drug-Induced Apoptosis

2001 ◽  
Vol 286 (2) ◽  
pp. 311-314 ◽  
Author(s):  
Neeladri Das ◽  
Sayan Gupta ◽  
Shyamalava Mazumdar
Keyword(s):  
Cytochrome C ◽  
Direct Observation ◽  
Drug Induced ◽  
Induced Apoptosis

scholarly journals Contribution of Mitochondrial Ion Channels to Chemo-Resistance in Cancer Cells

Cancers ◽  
2019 ◽  
Vol 11 (6) ◽  
pp. 761 ◽  
Author(s):  
Roberta Peruzzo ◽  
Ildiko Szabo
Keyword(s):  
Ion Channels ◽  
Cytochrome C ◽  
Cancer Cells ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Point Of No Return ◽  
Different Types ◽  
Subsequent Activation ◽  
Induced Apoptosis ◽  
Potential Efficiency

Mitochondrial ion channels are emerging oncological targets, as modulation of these ion-transporting proteins may impact on mitochondrial membrane potential, efficiency of oxidative phosphorylation and reactive oxygen production. In turn, these factors affect the release of cytochrome c, which is the point of no return during mitochondrial apoptosis. Many of the currently used chemotherapeutics induce programmed cell death causing damage to DNA and subsequent activation of p53-dependent pathways that finally leads to cytochrome c release from the mitochondrial inter-membrane space. The view is emerging, as summarized in the present review, that ion channels located in this organelle may account in several cases for the resistance that cancer cells can develop against classical chemotherapeutics, by preventing drug-induced apoptosis. Thus, pharmacological modulation of these channel activities might be beneficial to fight chemo-resistance of different types of cancer cells.

scholarly journals Requirement of Apaf-1 for mitochondrial events and the cleavage or activation of all procaspases during genotoxic stress-induced apoptosis

2007 ◽  
Vol 405 (1) ◽  
pp. 115-122 ◽  
Author(s):  
Emily E. Franklin ◽  
John D. Robertson
Keyword(s):  
Cytochrome C ◽  
Genotoxic Stress ◽  
Jurkat Cells ◽  
Mitochondrial Outer Membrane ◽  
Cytochrome C Release ◽  
Drug Induced ◽  
Mitochondrial Outer Membrane Permeabilization ◽  
Caspase 2 ◽  
Induced Apoptosis

Sequential activation of caspases is critical for the execution of apoptosis. Recent evidence suggests caspase 2 is a significant upstream caspase capable of initiating mitochondrial events, such as the release of cytochrome c. In particular, in vitro studies using recombinant proteins have shown that cleaved caspase 2 can induce mitochondrial outer membrane permeabilization directly or by cleaving the BH3-only protein BID (BH3 interacting domain death agonist). However, whether interchain cleavage or activation of procaspase 2 occurs prior to Apaf-1-mediated procaspase 9 activation under more natural conditions remains unresolved. In the present study, we show that Apaf-1-deficient Jurkat T-lymphocytes and mouse embryonic fibroblasts were highly resistant to DNA-damage-induced apoptosis and failed to cleave or activate any apoptotic procaspase, including caspase 2. Significantly, drug-induced cytochrome c release and loss of mitochondrial membrane potential were inhibited in cells lacking Apaf-1. By comparison, procaspase proteolysis and apoptosis were only delayed slightly in Apaf-1-deficient Jurkat cells upon treatment with anti-Fas antibody. Our data support a model in which Apaf-1 is necessary for the cleavage or activation of all procaspases and the promotion of mitochondrial apoptotic events induced by genotoxic drugs.

scholarly journals Changes in Endoplasmic Reticulum Luminal Environment Affect Cell Sensitivity to Apoptosis

2000 ◽  
Vol 150 (4) ◽  
pp. 731-740 ◽  
Author(s):  
Kimitoshi Nakamura ◽  
Ella Bossy-Wetzel ◽  
Kimberly Burns ◽  
Marc P. Fadel ◽  
Mira Lozyk ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Internal Factor ◽  
Drug Induced ◽  
Cell Sensitivity ◽  
Hela Cell Lines ◽  
Increased Sensitivity ◽  
Low Levels ◽  
Drug Dependent ◽  
Induced Apoptosis

To test the role of ER luminal environment in apoptosis, we generated HeLa cell lines inducible with respect to calreticulin and calnexin and investigated their sensitivity to drug-dependent apoptosis. Overexpression of calreticulin, an ER luminal protein, resulted in an increased sensitivity of the cells to both thapsigargin- and staurosporine-induced apoptosis. This correlated with an increased release of cytochrome c from the mitochondria. Overexpression of calnexin, an integral ER membrane protein, had no significant effect on drug-induced apoptosis. In contrast, calreticulin-deficient cells were significantly resistant to apoptosis and this resistance correlated with a decreased release of cytochrome c from mitochondria and low levels of caspase 3 activity. This work indicates that changes in the lumen of the ER amplify the release of cytochrome c from mitochondria, and increase caspase activity, during drug-induced apoptosis. There may be communication between the ER and mitochondria, which may involve Ca2+ and play an important role in conferring cell sensitivity to apoptosis. Apoptosis may depend on both the presence of external apoptosis-activating signals, and, as shown in this study, on an internal factor represented by the ER.

Upon Drug-Induced Apoptosis Expression of Prostate-apoptosis-response-gene-4 Promotes Cleavage of Caspase-8, Bid and Mitochondrial Release of Cytochrome c

Hematology ◽  
2004 ◽  
Vol 9 (5-6) ◽  
pp. 425-431 ◽  
Author(s):  
Simone Boehrer ◽  
Natasa Kukoc-Zivojnov ◽  
Daniel Nowak ◽  
Marion Bergmann ◽  
Christine Baum ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Caspase 8 ◽  
Response Gene ◽  
Drug Induced ◽  
Induced Apoptosis ◽  
Gene 4

Implication of Raft Microdomains in Drug Induced Apoptosis

2003 ◽  
Vol 3 (4) ◽  
pp. 263-270 ◽  
Author(s):  
Christine Bezombes ◽  
Guy Laurent ◽  
Jean-Pierre Jaffrezou
Keyword(s):  
Drug Induced ◽  
Induced Apoptosis

scholarly journals Sensitization for death receptor- or drug-induced apoptosis by re-expression of caspase-8 through demethylation or gene transfer

Oncogene ◽  
2001 ◽  
Vol 20 (41) ◽  
pp. 5865-5877 ◽  
Author(s):  
Simone Fulda ◽  
Martin U Küfer ◽  
Eric Meyer ◽  
Frans van Valen ◽  
Barbara Dockhorn-Dworniczak ◽  
...  
Keyword(s):  
Gene Transfer ◽  
Death Receptor ◽  
Caspase 8 ◽  
Drug Induced ◽  
Or Gene ◽  
Induced Apoptosis
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