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10 August 2018 Autophagy-Src Regulates Connexin43-Mediated Gap Junction Intercellular Communication in Irradiated HepG2 Cells
Xiaoyao Yang, Shengmin Xu, Yao Su, Biao Chen, Hang Yuan, An Xu, Lijun Wu
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Abstract

Connexin molecules are an important component of the gap junction, with connexin43 (Cx43) being the most abundantly expressed type. Src is a nonreceptor tyrosine-protein kinase that affects Cx43 activity by multiple mechanisms. However, it is not clear how Src regulates Cx43 to influence radiation-induced bystander effects (RIBEs). In this study, we demonstrated that Cx43 on Tyr265 was phosphorylated by activated Src in α-irradiated HepG2 cells, with the total expression of Cx43 unchanged. After inhibition of Cx43 phosphorylation in irradiated cells, the frequency of γ-H2AX foci formation in adjacent nonirradiated bystander cells was significantly enhanced. Furthermore, this study showed that autophagy regulated the activity of Src and phosphorylation of Cx43, and the level of autophagy was correlated with the radiation-induced reactive oxygen species (ROS). These results suggest that ROS and autophagy play an important role in regulating the Src-Cx43 axis to affect the RIBEs. Our findings provide new insights into the Cx43-mediated gap junction intercellular communication, as well as the underlying mechanism of RIBEs.

©2018 by Radiation Research Society.
Xiaoyao Yang, Shengmin Xu, Yao Su, Biao Chen, Hang Yuan, An Xu, and Lijun Wu "Autophagy-Src Regulates Connexin43-Mediated Gap Junction Intercellular Communication in Irradiated HepG2 Cells," Radiation Research 190(5), 494-503, (10 August 2018). https://doi.org/10.1667/RR15073.1
Received: 5 March 2018; Accepted: 11 July 2018; Published: 10 August 2018
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