Caspase-independent cell death mediated by apoptosis-inducing factor (AIF) nuclear translocation is involved in ionizing radiation induced HepG2 cell death

2016 ◽  
Vol 472 (1) ◽  
pp. 137-143 ◽  
Author(s):  
Hengwen Sun ◽  
Shana Yang ◽  
Jianhua Li ◽  
Yajie Zhang ◽  
Dongsheng Gao ◽  
...  
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Hepg2 Cell ◽  
Nuclear Translocation ◽  
Radiation Induced ◽  
Apoptosis Inducing Factor

scholarly journals Inhibition of Rac1 attenuates radiation-induced lung injury while suppresses lung tumor in mice

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Ni An ◽  
Zhenjie Li ◽  
Xiaodi Yan ◽  
Hainan Zhao ◽  
Yajie Yang ◽  
...  
Keyword(s):  
Ionizing Radiation ◽  
Lung Injury ◽  
Mouse Model ◽  
Tumor Cells ◽  
Nuclear Translocation ◽  
Lung Tumor ◽  
Lung Epithelial Cells ◽  
Normal Lung ◽  
Limiting Factor ◽  
Radiation Induced

AbstractThe lung is one of the most sensitive tissues to ionizing radiation, thus, radiation-induced lung injury (RILI) stays a key dose-limiting factor of thoracic radiotherapy. However, there is still little progress in the effective treatment of RILI. Ras-related C3 botulinum toxin substrate1, Rac1, is a small guanosine triphosphatases involved in oxidative stress and apoptosis. Thus, Rac1 may be an important molecule that mediates radiation damage, inhibition of which may produce a protective effect on RILI. By establishing a mouse model of radiation-induced lung injury and orthotopic lung tumor-bearing mouse model, we detected the role of Rac1 inhibition in the protection of RILI and suppression of lung tumor. The results showed that ionizing radiation induces the nuclear translocation of Rac1, the latter then promotes nuclear translocation of P53 and prolongs the residence time of p53 in the nucleus, thereby promoting the transcription of Trp53inp1 which mediates p53-dependent apoptosis. Inhibition of Rac1 significantly reduce the apoptosis of normal lung epithelial cells, thereby effectively alleviating RILI. On the other hand, inhibition of Rac1 could also significantly inhibit the growth of lung tumor, increase the radiation sensitivity of tumor cells. These differential effects of Rac1 inhibition were related to the mutation and overexpression of Rac1 in tumor cells.

scholarly journals Nuclear Translocation of Apoptosis-Inducing Factor after Focal Cerebral Ischemia

2004 ◽  
Vol 24 (4) ◽  
pp. 458-466 ◽  
Author(s):  
Nikolaus Plesnila ◽  
Changlian Zhu ◽  
Carsten Culmsee ◽  
Moritz Gröger ◽  
Michael A. Moskowitz ◽  
...  
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Cytochrome C ◽  
Nuclear Translocation ◽  
Focal Cerebral Ischemia ◽  
Mitochondrial Protein ◽  
Neuronal Cell ◽  
Experimental Stroke ◽  
Cytochrome C Release ◽  
Apoptosis Inducing Factor

Signaling cascades associated with apoptosis contribute to cell death after focal cerebral ischemia. Cytochrome c release from mitochondria and the subsequent activation of caspases 9 and 3 are critical steps. Recently, a novel mitochondrial protein, apoptosis-inducing factor (AIF), has been implicated in caspase-independent programmed cell death following its translocation to the nucleus. We, therefore, addressed the question whether AIF also plays a role in cell death after focal cerebral ischemia. We detected AIF relocation from mitochondria to nucleus in primary cultured rat neurons 4 and 8 hours after 4 hours of oxygen/glucose deprivation. In ischemic mouse brain, AIF was detected within the nucleus 1 hour after reperfusion after 45 minutes occlusion of the middle cerebral artery. AIF translocation preceded cell death, occurred before or at the time when cytochrome c was released from mitochondria, and was evident within cells showing apoptosis-related DNA fragmentation. From these findings, we infer that AIF may be involved in neuronal cell death after focal cerebral ischemia and that caspase-independent signaling pathways downstream of mitochondria may play a role in apoptotic-like cell death after experimental stroke.

scholarly journals Pharmacologic Profiling of Phosphoinositide 3-Kinase Inhibitors as Mitigators of Ionizing Radiation–Induced Cell Death

2013 ◽  
Vol 347 (3) ◽  
pp. 669-680 ◽  
Author(s):  
John S. Lazo ◽  
Elizabeth R. Sharlow ◽  
Michael W. Epperly ◽  
Ana Lira ◽  
Stephanie Leimgruber ◽  
...  
Keyword(s):  
Cell Death ◽  
Ionizing Radiation ◽  
Kinase Inhibitors ◽  
Radiation Induced ◽  
Phosphoinositide 3 Kinase

Chemical chaperones reduce ionizing radiation-induced endoplasmic reticulum stress and cell death in IEC-6 cells

2014 ◽  
Vol 450 (2) ◽  
pp. 1005-1009 ◽  
Author(s):  
Eun Sang Lee ◽  
Hae-June Lee ◽  
Yoon-Jin Lee ◽  
Jae-Hoon Jeong ◽  
Seongman Kang ◽  
...  
Keyword(s):  
Endoplasmic Reticulum ◽  
Cell Death ◽  
Ionizing Radiation ◽  
Endoplasmic Reticulum Stress ◽  
Chemical Chaperones ◽  
Radiation Induced
Sign in / Sign up

Export Citation Format

Share Document