Role of NADPH Oxidase and Calcium in Cerulein-Induced Apoptosis: Involvement of Apoptosis-Inducing Factor

2006 ◽  
Vol 1090 (1) ◽  
pp. 292-297 ◽  
Author(s):  
J. H. YU ◽  
K. H. KIM ◽  
H. KIM
Keyword(s):  
Nadph Oxidase ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor

scholarly journals Caspase-Independent Pathway is Related to Nilotinib Cytotoxicity in Cultured Cardiomyocytes

2017 ◽  
Vol 42 (6) ◽  
pp. 2182-2193 ◽  
Author(s):  
Qinghui Yang ◽  
Chunhui Zhang ◽  
Hong Wei ◽  
Zenghui Meng ◽  
Guangnan Li ◽  
...  
Keyword(s):  
Cathepsin B ◽  
Nuclear Translocation ◽  
Morphological Changes ◽  
H9c2 Cells ◽  
Mitochondrial Signaling ◽  
Leukemia Treatment ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor ◽  
Cultured Cardiomyocytes

Background/Aims: Cardiotoxicity is a predominant side-effect of nilotinib during chronic myeloid leukemia treatment. The underlying molecular mechanism remains unclear. The role of autophagy and mitochondrial signaling was investigated in nilotinib-treated cardiac H9C2 cells. Methods: Cytotoxicity was assessed using Cell Death Detection kit. Immunoblot and immunofluorescence staining was performed, and cathepsin B and caspase3 activity was assessed in nilotinib-treated H9C2 cells with or without distinct pathway inhibitor or specific siRNA. Results: Nilotinib time- and dose-dependently induced H9C2 apoptosis, which was not completely prevented by the pan caspase inhibitor z-VAD-fmk. Following nilotinib treatment, mitochondrial membrane potential decreased significantly accompanied with remarkable morphological changes. Nuclear translocation of mitochondrial apoptosis inducing factor (AIF) and increased p53 was detected in nilotinib-treated cells. AIF knockdown prevented nilotinib-induced increase of p53 and apoptosis. Additionally, increased cathepsin B activity was detected, and inhibition of cathepsin B by CA-074Me prevented nilotinib-induced apoptosis and nuclear translocation of AIF. Moreover, increased Atg5 and transition of LC3-I to LC3-II was revealed following nilotinib treatment. Increased cathepsin B activity and apoptosis by nilotinib was significantly prohibited by specific autophagy inhibitor bafilomycin A and Atg5 knockdown. Conclusion: Our findings demonstrate that nilotinib increases autophagy and cathepsin B activity, leading to mitochondrial AIF release and nuclear translocation, which is responsible for p53 and apoptosis induction in H9C2 cells.

scholarly journals Role of caspases and apoptosis-inducing factor (AIF) in cladribine-induced apoptosis of B cell chronic lymphocytic leukemia

Leukemia ◽  
2002 ◽  
Vol 16 (10) ◽  
pp. 2106-2114 ◽  
Author(s):  
P Pérez-Galán ◽  
I Marzo ◽  
P Giraldo ◽  
D Rubio-Félix ◽  
P Lasierra ◽  
...  
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Lymphocytic Leukemia ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor ◽  
Cell Chronic Lymphocytic Leukemia

Inhibitory effect of selaginellin on high glucose-induced apoptosis in differentiated PC12 cells: Role of NADPH oxidase and LOX-1

2012 ◽  
Vol 694 (1-3) ◽  
pp. 60-68 ◽  
Author(s):  
Wei-Fang Zhang ◽  
Ya-Yong Xu ◽  
Kang-Ping Xu ◽  
Wei-Hua Wu ◽  
Gui-Shan Tan ◽  
...  
Keyword(s):  
Nadph Oxidase ◽  
Pc12 Cells ◽  
High Glucose ◽  
Inhibitory Effect ◽  
Differentiated Pc12 Cells ◽  
Induced Apoptosis

scholarly journals Selenite-induced cell death in Saccharomyces cerevisiae: protective role of glutaredoxins

Microbiology ◽  
2010 ◽  
Vol 156 (9) ◽  
pp. 2608-2620 ◽  
Author(s):  
Alicia Izquierdo ◽  
Celia Casas ◽  
Enrique Herrero
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Membrane Integrity ◽  
Protective Role ◽  
Protein Carbonylation ◽  
Yeast Cells ◽  
Yeast Cultures ◽  
High Concentrations ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor

Unlike in higher organisms, selenium is not essential for growth in Saccharomyces cerevisiae. In this species, it causes toxic effects at high concentrations. In the present study, we show that when supplied as selenite to yeast cultures growing under fermentative metabolism, its effects can be dissected into two death phases. From the time of initial treatment, it causes loss of membrane integrity and genotoxicity. Both effects occur at higher levels in mutants lacking Grx1p and Grx2p than in wild-type cells, and are reversed by expression of a cytosolic version of the membrane-associated Grx7p glutaredoxin. Grx7p can also rescue the high levels of protein carbonylation damage that occur in selenite-treated cultures of the grx1 grx2 mutant. After longer incubation times, selenite causes abnormal nuclear morphology and the appearance of TUNEL-positive cells, which are considered apoptotic markers in yeast cells. This effect is independent of Grx1p and Grx2p. Therefore, the protective role of the two glutaredoxins is restricted to the initial stages of selenite treatment. Lack of Yca1p metacaspase or of a functional mitochondrial electron transport chain only moderately diminishes apoptotic-like death by selenite. In contrast, selenite-induced apoptosis is dependent on the apoptosis-inducing factor Aif1p. In the absence of the latter, intracellular protein carbonylation is reduced after prolonged selenite treatment, supporting the supposition that part of the oxidative damage is contributed by apoptotic cells.

scholarly journals A Role of the Mitochondrial Apoptosis-Inducing Factor in Granulysin-Induced Apoptosis

2001 ◽  
Vol 167 (3) ◽  
pp. 1222-1229 ◽  
Author(s):  
Julián Pardo ◽  
Patricia Pérez-Galán ◽  
Susana Gamen ◽  
Isabel Marzo ◽  
Inmaculada Monleón ◽  
...  
Keyword(s):  
Mitochondrial Apoptosis ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor

scholarly journals Nuclear HKII–P-p53 (Ser15) Interaction is a Prognostic Biomarker for Chemoresponsiveness and Glycolytic Regulation in Epithelial Ovarian Cancer

Cancers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 3399
Author(s):  
Chae Han ◽  
David Patten ◽  
Se Kim ◽  
Jung Lim ◽  
David Chan ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Epithelial Ovarian Cancer ◽  
Prognostic Biomarker ◽  
Aerobic Glycolysis ◽  
Glycolytic Enzyme ◽  
Hexokinase Ii ◽  
Proximity Ligation ◽  
Induced Apoptosis ◽  
Apoptosis Inducing Factor

In epithelial ovarian cancer (EOC), carboplatin/cisplatin-induced chemoresistance is a major hurdle to successful treatment. Aerobic glycolysis is a common characteristic of cancer. However, the role of glycolytic metabolism in chemoresistance and its impact on clinical outcomes in EOC are not clear. Here, we show a functional interaction between the key glycolytic enzyme hexokinase II (HKII) and activated P-p53 (Ser15) in the regulation of bioenergetics and chemosensitivity. Using translational approaches with proximity ligation assessment in cancer cells and human EOC tumor sections, we showed that nuclear HKII–P-p53 (Ser15) interaction is increased after chemotherapy, and functions as a determinant of chemoresponsiveness as a prognostic biomarker. We also demonstrated that p53 is required for the intracellular nuclear HKII trafficking in the control of glycolysis in EOC, associated with chemosensitivity. Mechanistically, cisplatin-induced P-p53 (Ser15) recruits HKII and apoptosis-inducing factor (AIF) in chemosensitive EOC cells, enabling their translocation from the mitochondria to the nucleus, eliciting AIF-induced apoptosis. Conversely, in p53-defective chemoresistant EOC cells, HKII and AIF are strongly bound in the mitochondria and, therefore, apoptosis is suppressed. Collectively, our findings implicate nuclear HKII–P-p53(Ser15) interaction in chemosensitivity and could provide an effective clinical strategy as a promising biomarker during platinum-based therapy.

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