The reactive oxygen species-Src-Stat3 pathway provokes negative feedback inhibition of apoptosis induced by high-fluence low-power laser irradiation.
High-fluence low-power laser irradiation (HF-LPLI) can induce apoptosis by triggering mitochondrial oxidative stress. Signal transducer and activator of transcription 3 (Stat3) is an important transcription factor in the modulation of cell proliferation and apoptosis. Here, using real-time single-cell analysis and western blotting analysis, we investigated the changes in activities of Stat3 in COS-7 cells upon HF-LPLI (633 nm, 80 and 120 J·cm(-2)) and the underlying mechanisms involved. We found that Stat3 was significantly activated by HF-LPLI in a time-dependent and dose-dependent manner. Stat3 activation attenuated HF-LPLI-induced apoptosis, as shown by the fact that both dominant negative Stat3 (Y705F) and Stat3 small interfering RNA expression enhanced cellular apoptosis induced by HF-LPLI. Moreover, we also found that Src kinase was the major positive regulator of Stat3 activation induced by HF-LPLI. Reactive oxygen species (ROS) generation was essential for Stat3 and Src activation upon HF-LPLI, because scavenging of ROS by vitamin C or N-acetylcysteine totally abrogated the activation of Stat3 and Src. Taken together, these findings show that the ROS-Src-Stat3 pathway mediates a negative feedback inhibition of apoptosis induced by HF-LPLI in COS-7 cells. Our research will provide new insights into the mechanism of apoptosis caused by HF-LPLI, and also extend the functional study of Stat3.
MOE Key Laboratory of Laser Life Science & Institute of Laser Life Science, College of Biophotonics, South China Normal University, Guangzhou, China.
Xuegang
X
Sun
Shengnan
S
Wu
Da
D
Xing
D000818:Animals; D017209:Apoptosis / Q000528:radiation effects*; D019556:COS Cells; D002522:Chlorocebus aethiops; D004307:Dose-Response Relationship, Radiation; D025461:Feedback, Physiological; D031541:Fluorescence Resonance Energy Transfer; D017930:Genes, Reporter; D028022:Low-Level Light Therapy; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000528:radiation effects; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D050796:STAT3 Transcription Factor; D019061:src-Family Kinases