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학술연구/단체지원/교육 등 연구자 활동을 지속하도록 DBpia가 지원하고 있어요.
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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2020.1
- 수록면
- 264 - 275 (12page)
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Reactive oxygen species (ROS) play a significant role in intracellular signaling and regulation, particularly when they are maintained at physiologic levels. However, excess ROS can cause cell damage and induce cell death. We recently reported that eIF2α phosphorylation protects hepatocytes from oxidative stress and liver fibrosis induced by fructose metabolism. Here, we found that hepatocyte-specific eIF2α phosphorylation-deficient mice have significantly reduced expression of the epidermal growth factor receptor (EGFR) and altered EGFR-mediated signaling pathways. EGFR-mediated signaling pathways are important for cell proliferation, differentiation, and survival in many tissues and cell types. Therefore, we studied whether the reduced amount of EGFR is responsible for the eIF2α phosphorylationdeficient hepatocytes’ vulnerability to oxidative stress. ROS such as hydrogen peroxide and superoxides induce both EGFR tyrosine phosphorylation and eIF2α phosphorylation. eIF2α phosphorylation-deficient primary hepatocytes, or EGFR knockdown cells, have decreased ROS scavenging ability compared to normal cells. Therefore, these cells are particularly susceptible to oxidative stress. However, overexpression of EGFR in these eIF2α phosphorylationdeficient primary hepatocytes increased ROS scavenging ability and alleviated ROS-mediated cell death. Therefore, we hypothesize that the reduced EGFR level in eIF2α phosphorylation-deficient hepatocytes is one of critical factors responsible for their susceptibility to oxidative stress.
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참고문헌 (52)
참고문헌 신청
Abdelmohsen, K. / 2003 / Epidermal growth factor receptor is a common mediator of quinone-induced signaling leading to phosphorylation of connexin-43 : role of glutathione and tyrosine phosphatases / J. Biol. Chem 278:38360~38367
Back, S. H. / 2009 / Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells / Cell Metab 10:13~26
Berasain, C. / 2014 / The EGFR signalling system in the liver : from hepatoprotection to hepatocarcinogenesis / J. Gastroenterol 49:9~23
Brunet, A. / 1999 / Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor / Cell 96:857~868
Carballo, M. / 1999 / Oxidative stress triggers STAT3 tyrosine phosphorylation and nuclear translocation in human lymphocytes / J. Biol. Chem 274:17580~17586
Back, S. H. / 2009 / Translation attenuation through eIF2alpha phosphorylation prevents oxidative stress and maintains the differentiated state in beta cells / Cell Metab 10:13~26
Berasain, C. / 2014 / The EGFR signalling system in the liver : from hepatoprotection to hepatocarcinogenesis / J. Gastroenterol 49:9~23
Brunet, A. / 1999 / Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor / Cell 96:857~868
Carballo, M. / 1999 / Oxidative stress triggers STAT3 tyrosine phosphorylation and nuclear translocation in human lymphocytes / J. Biol. Chem 274:17580~17586
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