scholarly journals Baculovirus P35 inhibits NO-induced apoptosis in activated macrophages by inhibiting cytochrome c release

2004 ◽  
Vol 117 (14) ◽  
pp. 3031-3039 ◽  
Author(s):  
P. Ranjan
Keyword(s):  
Cytochrome C ◽  
Activated Macrophages ◽  
Cytochrome C Release ◽  
Baculovirus P35 ◽  
Induced Apoptosis

Prevention of TNF-α-induced apoptosis in polyamine-depleted IEC-6 cells is mediated through the activation of ERK1/2

2004 ◽  
Vol 286 (3) ◽  
pp. G479-G490 ◽  
Author(s):  
Sujoy Bhattacharya ◽  
Ramesh M. Ray ◽  
Leonard R. Johnson
Keyword(s):  
Epithelial Cells ◽  
Cytochrome C ◽  
Critical Role ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Cytochrome C Release ◽  
Erk Phosphorylation ◽  
Tnf Α ◽  
Induced Apoptosis ◽  
Jnk Activation

It has been documented that polyamines play a critical role in the regulation of apoptosis in intestinal epithelial cells. We have recently reported that protection from TNF-α/cycloheximide (CHX)-induced apoptosis in epithelial cells depleted of polyamines is mediated through the inactivation of a proapoptotic mediator, JNK. In this study, we addressed the involvement of the MAPK pathway in the regulation of apoptosis after polyamine depletion of IEC-6 cells. Polyamine depletion by α-difluromethylornithine (DFMO) resulted in the sustained activation of ERK in response to TNF-α/CHX treatment. Pretreatment of polyamine-depleted IEC-6 cells with a cell membrane-permeable MEK1/2 inhibitor, U-0126, significantly inhibited TNF-α/CHX-induced ERK phosphorylation and significantly increased DNA fragmentation, JNK activity, and caspase-3 activity in response to TNF-α/CHX. Moreover, the dose dependency of U-0126-mediated inhibition of TNF-α/ CHX-induced ERK phosphorylation correlated with the reversal of the antiapoptotic effect of DFMO. IEC-6 cells expressing constitutively active MEK1 had decreased TNF-α/CHX-induced JNK phosphorylation and were significantly protected from apoptosis. Conversely, a dominant-negative MEK1 resulted in high basal activation of JNK, cytochrome c release, and spontaneous apoptosis. Polyamine depletion of the dominant-negative MEK1 cells did not prevent JNK activation or cytochrome c release and failed to confer protection from both TNF-α/CHX and camptothecin-induced apoptosis. Finally, expression of a dominant-negative mutant of JNK significantly protected IEC-6 cells from TNF-α/CHX-induced apoptosis. These data indicate that polyamine depletion results in the activation of ERK, which inhibits JNK activation and protects cells from 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 Sirt5 Attenuates Cisplatin-Induced Acute Kidney Injury through Regulation of Nrf2/HO-1 and Bcl-2

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Wei Li ◽  
Yuanyuan Yang ◽  
You Li ◽  
Yueyue Zhao ◽  
Hong Jiang
Keyword(s):  
Acute Kidney Injury ◽  
Cytochrome C ◽  
Kidney Injury ◽  
Human Kidney ◽  
Dependent Manner ◽  
Cytochrome C Release ◽  
Bax Protein ◽  
Intracellular Ros ◽  
Induced Apoptosis ◽  
Mitotracker Red

Cisplatin- (CDDP) induced acute kidney injury (AKI) limits the clinical use of cisplatin. Several sirtuin (SIRT) family proteins are involved in AKI, while the roles of Sirt5 in cisplatin-induced AKI remain unknown. In the present study, we characterized the role and mechanism of Sirt5 in cisplatin-induced apoptosis using the human kidney 2 (HK-2) cell line. CDDP treatment decreased Sirt5 expression of HK-2 cells in a dose-dependent manner. In addition, Sirt5 overexpression enhanced the metabolic activity in CDDP-treated HK-2 cells while Sirt5 siRNA attenuated it. Forced expression of Sirt5 inhibited CDDP-induced apoptosis while Sirt5 siRNA showed the opposite effects. Accordingly, Sirt5 overexpression inhibited the level of caspase 3 cleavage and cytochrome c levels. Furthermore, we found that Sirt5 increased mitochondrial membrane potentials and ameliorated intracellular ROS production. Mitotracker Red staining indicated that Sirt5 overexpression was able to maintain the mitochondrial density during CDDP treatment. We also investigated possible downstream targets of Sirt5 and found that Sirt5 increased Nrf2, HO-1, and Bcl-2 while it decreased Bax protein expression. Sirt5 siRNA showed the opposite effect on these proteins. The levels of Nrf2, HO-1, and Bcl-2 proteins in HK-2 cells were also decreased after CDDP treatment. Moreover, Nrf2 and Bcl-2 siRNA partly abolished the protecting effect of Sirt5 on CDDP-induced apoptosis and cytochrome c release. Catalase inhibitor 3-AT also abolished the cytoprotective effect of Sirt5. Together, the results demonstrated that Sirt5 attenuated cisplatin-induced apoptosis and mitochondrial injury in human kidney HK-2 cells, possibly through the regulation of Nrf2/HO-1 and Bcl-2.

Nitric Oxide–Induced Apoptosis in Human Leukemic Lines Requires Mitochondrial Lipid Degradation and Cytochrome C Release

Blood ◽  
1999 ◽  
Vol 93 (7) ◽  
pp. 2342-2352 ◽  
Author(s):  
Alexey Ushmorov ◽  
Frank Ratter ◽  
Volker Lehmann ◽  
Wulf Dröge ◽  
Volker Schirrmacher ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Cytochrome C ◽  
Mitochondrial Protein ◽  
Jurkat Cells ◽  
Leukemic Cells ◽  
Human Leukemia ◽  
Cytochrome C Release ◽  
Mitochondrial Functions ◽  
Mitochondrial Lipid ◽  
Induced Apoptosis

Abstract We have previously shown that nitric oxide (NO) stimulates apoptosis in different human neoplastic lymphoid cell lines through activation of caspases not only via CD95/CD95L interaction, but also independently of such death receptors. Here we investigated mitochondria-dependent mechanisms of NO-induced apoptosis in Jurkat leukemic cells. NO donor glycerol trinitrate (at the concentration, which induces apoptotic cell death) caused (1) a significant decrease in the concentration of cardiolipin, a major mitochondrial lipid; (2) a downregulation in respiratory chain complex activities; (3) a release of the mitochondrial protein cytochrome c into the cytosol; and (4) an activation of caspase-9 and caspase-3. These changes were accompanied by an increase in the number of cells with low mitochondrial transmembrane potential and with a high level of reactive oxygen species production. Higher resistance of the CD95-resistant Jurkat subclone (APO-R) cells to NO-mediated apoptosis correlated with the absence of cytochrome c release and with less alterations in other mitochondrial parameters. An inhibitor of lipid peroxidation, trolox, significantly suppressed NO-mediated apoptosis in APO-S Jurkat cells, whereas bongkrekic acid (BA), which blocks mitochondrial permeability transition, provided only a moderate antiapoptotic effect. Transfection of Jurkat cells with bcl-2 led to a complete block of apoptosis due to the prevention of changes in mitochondrial functions. We suggest that the mitochondrial damage (in particular, cardiolipin degradation and cytochrome c release) induced by NO in human leukemia cells plays a crucial role in the subsequent activation of caspase and apoptosis.

scholarly journals Sensitization to CD95 ligand-induced apoptosis in human glioma cells by hyperthermia involves enhanced cytochrome c release

Oncogene ◽  
2000 ◽  
Vol 19 (19) ◽  
pp. 2338-2345 ◽  
Author(s):  
Mirjam Hermisson ◽  
Bettina Wagenknecht ◽  
Hartwig Wolburg ◽  
Tamara Glaser ◽  
Johannes Dichgans ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Glioma Cells ◽  
Human Glioma ◽  
Human Glioma Cells ◽  
Cytochrome C Release ◽  
Cd95 Ligand ◽  
Induced Apoptosis

Resistance of leukemic cells to 2-chlorodeoxyadenosine is due to a lack of calcium-dependent cytochrome c release

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 655-663 ◽  
Author(s):  
Joya Chandra ◽  
Emma Mansson ◽  
Vladimir Gogvadze ◽  
Scott H. Kaufmann ◽  
Freidoun Albertioni ◽  
...  
Keyword(s):  
Cytochrome C ◽  
Dna Fragmentation ◽  
Cell Lines ◽  
Resistant Cell ◽  
Leukemic Cells ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Deoxyguanosine Kinase ◽  
Induced Apoptosis ◽  
Resistant Cells

Abstract The purine nucleoside 2-chlorodeoxyadenosine (CdA) is often used in leukemia therapy. Its efficacy, however, is compromised by the emergence of resistant cells. In the present study, 3 CdA-resistant cell lines were generated and characterized. Their ability to accumulate 2-chloroadenosine triphosphate (CdATP) varied, reflecting differences in activities of deoxycytidine kinase (dCK) and deoxyguanosine kinase (dGK). Nonetheless, the selected lines were uniformly resistant to CdA-induced apoptosis, as assessed by caspase activation and DNA fragmentation. In contrast, cytosols from resistant cells were capable of robust caspase activation when incubated in the presence of cytochrome c and dATP. Moreover, replacement of dATP with CdATP also resulted in caspase activation in the parental and some of the resistant cell lines. Strikingly, CdA-induced decreases in mitochondrial transmembrane potential and release of cytochrome c from mitochondria were observed in the parental cells but not in any resistant lines. The lack of cytochrome c release correlated with an increased ability of mitochondria from resistant cells to sequester free Ca2+. Consistent with this enhanced Ca2+buffering capacity, an early increase in cytosolic Ca2+after CdA treatment of parental cells but not resistant cells was detected. Furthermore, CdA-resistant cells were selectively cross-resistant to thapsigargin but not to staurosporine- or Fas-induced apoptosis. In addition, CdA-induced caspase-3 activation and DNA fragmentation were inhibited by the Ca2+ chelator BAPTA-AM in sensitive cells. Taken together, the data indicate that the mechanism of resistance to CdA may be dictated by changes in Ca2+-sensitive mitochondrial events.

scholarly journals Cisplatin-induced apoptosis in p53-deficient renal cells via the intrinsic mitochondrial pathway

2009 ◽  
Vol 296 (5) ◽  
pp. F983-F993 ◽  
Author(s):  
Man Jiang ◽  
Cong-Yi Wang ◽  
Shuang Huang ◽  
Tianxin Yang ◽  
Zheng Dong
Keyword(s):  
Cytochrome C ◽  
Primary Cultures ◽  
Mitochondrial Pathway ◽  
Limiting Factor ◽  
Double Knockout ◽  
Cytochrome C Release ◽  
Renal Tubular Cells ◽  
In The Wild ◽  
Renal Tubular ◽  
Induced Apoptosis

Nephrotoxicity is the major limiting factor for the use of cisplatin in cancer therapy. Recent studies have demonstrated an important role for p53 in cisplatin-induced renal injury. Nevertheless, pharmacological and genetic blockade of p53 only provides partial renoprotective effects, suggesting the presence of p53-independent injury mechanisms. To understand the p53-independent mechanisms, we have now examined cisplatin-induced apoptosis in p53-deficient kidney cells. We show that cisplatin could induce Bax activation, cytochrome c release, and apoptosis in primary cultures of p53-deficient renal tubular cells, albeit at a level that was lower than in the wild-type cells. Cisplatin could also induce typical apoptosis in p53-deficient baby mouse kidney (BMK) cells. The apoptosis was caspase dependent and could be completely blocked by general caspase inhibitors. Bax and Bak, two key molecules in the mitochondrial pathway of apoptosis, were interdependently activated by cisplatin, with Bax translocation to and Bax/Bak oligomerization in mitochondria, leading to cytochrome c release. Importantly, cytochrome c release and apoptosis were diminished in Bax/Bak single or double-knockout BMK cells. Furthermore, overexpression of Bcl-2 could ameliorate cisplatin-induced cytochrome c release and apoptosis. Together, the results have demonstrated a p53-independent mechanism of cisplatin nephrotoxicity that involves the mitochondrial pathway of apoptosis.

scholarly journals Corrigendum to: Cytochrome c release and caspase activation in hydrogen peroxide- and tributyltin-induced apoptosis (FEBS 20394)

FEBS Letters ◽  
1998 ◽  
Vol 437 (1-2) ◽  
pp. 163-163 ◽  
Author(s):  
Hélène Stridh ◽  
Monica Kimland ◽  
Dean P. Jones ◽  
Sten Orrenius ◽  
Mark B. Hampton
Keyword(s):  
Hydrogen Peroxide ◽  
Cytochrome C ◽  
Caspase Activation ◽  
Cytochrome C Release ◽  
Induced Apoptosis
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