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Identification of Intracellular Signaling Events Induced in Viable Cells by Interaction with Neighboring Cells Undergoing Apoptotic Cell Death
Published on: December 27, 2016
Targeting protective autophagy exacerbates UV-triggered apoptotic cell death
Li-Hsin Chen1, Pei-Ming Chu2, Yi-Jang Lee3
1Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan.
International Journal of Molecular Sciences
|February 8, 2012
Summary
Ultraviolet (UV) irradiation triggers autophagy, a cellular process that protects cells from DNA damage-induced apoptosis. This protective autophagy response is mediated by ATR in early stages but becomes independent of ATR later on.
Area of Science:
- Cellular Biology
- Molecular Biology
- DNA Damage Response
Background:
- Autophagy is a cellular stress response activated by DNA damage.
- Previous research focused on chemotherapy, radiation, and oxidative stress-induced autophagy.
- The role of autophagy in response to ultraviolet (UV) irradiation requires further investigation.
Purpose of the Study:
- To investigate the biological significance of autophagic response to UV irradiation in human lung cancer cell lines (A549 and H1299).
- To elucidate the role of ATR (Ataxia Telangiectasia and Rad3-related) kinase in UV-induced autophagy.
Main Methods:
- UV irradiation of A549 and H1299 cells.
- Knockdown of autophagy-related genes (beclin-1, Atg5) and ATR.
- Assessment of autophagic flux using LC3B-II expression.
- Evaluation of cell viability and apoptosis.
Main Results:
- UV irradiation induced autophagic flux in A549 and H1299 cells.
- Inhibition of autophagy (beclin-1, Atg5 knockdown) reduced cell viability and increased apoptosis.
- ATR phosphorylation correlated with early-stage LC3B-II expression following UV exposure.
- ATR knockdown attenuated early-stage UV-induced LC3B-II reduction.
- ATR's role in autophagy induction diminished at later time points (24-48h post-UV), suggesting an ATR-independent pathway.
Conclusions:
- Autophagy functions as a cytoprotective mechanism against UV-induced apoptosis.
- Early-stage UV-induced autophagy involves ATR activation.
- Late-stage autophagy induction and apoptosis following UV irradiation are independent of ATR.
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