Abstract
Autophagy is activated by various stresses, including DNA damage, and previous studies of DNA damage-induced autophagy have focused on the response to chemotherapeutic drugs, ionizing radiation, and reactive oxygen species. In this study, we investigated the biological significance of autophagic response to ultraviolet (UV) irradiation in A549 and H1299 cells. Our results indicated that UV induces on-rate autophagic flux in these cells. Autophagy inhibition resulting from the knockdown of beclin-1 and Atg5 reduced cell viability and enhanced apoptosis. Moreover, we found that ATR phosphorylation was accompanied by microtubule-associated protein 1 light chain 3B II (LC3B-II) expression during the early phases following UV irradiation, which is a well-established inducer of ATR. Knocking down ATR further attenuated the reduction in LC3B-II at early stages in response to UV treatment. Despite the potential role of ATR in autophagic response, reduced ATR expression does not affect autophagy induction during late phases (24 and 48 h after UV treatment). The result is consistent with the reduced ATR phosphorylation at the same time points and suggests that autophagic response at this stage is activated via a distinct pathway. In conclusion, this study demonstrated that autophagy acts as a cytoprotective mechanism against UV-induced apoptosis and that autophagy induction accompanied with apoptosis at late stages is independent of ATR activation.
Highlights
IntroductionMacroautophagy (referred to as “autophagy” from this point onward) is an evolutionarily conserved process in which long-lived proteins and intact organelles are engulfed within double-membraned vacuoles (autophagosomes) and degraded after the vacuoles fuse with lysosomes (autophagolysosomes or autolysosomes)
Macroautophagy is an evolutionarily conserved process in which long-lived proteins and intact organelles are engulfed within double-membraned vacuoles and degraded after the vacuoles fuse with lysosomes
We examined whether UV irradiation could induce autophagy in the A549 and H1299 cells
Summary
Macroautophagy (referred to as “autophagy” from this point onward) is an evolutionarily conserved process in which long-lived proteins and intact organelles are engulfed within double-membraned vacuoles (autophagosomes) and degraded after the vacuoles fuse with lysosomes (autophagolysosomes or autolysosomes). At the end of the process, the degradation products are released into the cytosol and reutilized for metabolism. The molecular machinery of autophagy is tightly regulated by diverse signaling pathways that are activated in response to various stimuli. Autophagy can result in cell death if it is massively activated under certain stresses, an event which is referred to as programmed cell death type II [1]. Further evidence has indicated that autophagy functions as a cytoprotective response against various types of cellular stress by providing the cell with metabolic substrates
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