AQP8 Modulates Mitochondrial H₂O₂ Transport to Influence Glioma Proliferation

作者全名：Shen, ZiHao; Sheng, HuaJun; Zhao, Jing; Xu, Jin; Cai, ZiLing; Zhang, Hao; Guo, Zhen; Liu, JunNan; Liang, Hang; Tan, LiHao; Gan, ShengWei; Huang, Juan; Zhu, ShuJuan

作者地址：[Shen, ZiHao; Sheng, HuaJun; Xu, Jin; Cai, ZiLing; Zhang, Hao; Guo, Zhen; Liu, JunNan; Liang, Hang; Tan, LiHao; Gan, ShengWei; Huang, Juan; Zhu, ShuJuan] Chongqing Med Univ, Coll Basic Med, Dept Human Anat, 1st Yixueyuan Rd, Chongqing 400016, Peoples R China; [Shen, ZiHao; Sheng, HuaJun; Xu, Jin; Cai, ZiLing; Zhang, Hao; Guo, Zhen; Liu, JunNan; Liang, Hang; Tan, LiHao; Gan, ShengWei; Huang, Juan; Zhu, ShuJuan] Chongqing Med Univ, Neurosci Res Ctr, Chongqing, Peoples R China; [Zhao, Jing] Xian Hosp TCM, Xian, Peoples R China

通信作者：Zhu, SJ (通讯作者)，Chongqing Med Univ, Coll Basic Med, Dept Human Anat, 1st Yixueyuan Rd, Chongqing 400016, Peoples R China.

来源：CANCER INVESTIGATION

ESI学科分类：CLINICAL MEDICINE

WOS号：WOS:001222628100001

JCR分区：Q3

影响因子：1.8

年份：2024

卷号：42

期号：4

开始页：345

结束页：356

文献类型：Article

关键词：Aquaporin-8; glioma; mitochondria; ROS; p53/p21

摘要：Background: Aquaporin-8 (AQP8) is involved in impacting glioma proliferation and can effect tumour growth by regulating Intracellular reactive oxygen species (ROS) signalling levels. In addition to transporting H2O2, AQP8 has been shown to affect ROS signaling, but evidence is lacking in gliomas. In this study, we aimed to investigate how AQP8 affects ROS signaling in gliomas. Materials and methods: We constructed A172 and U251 cell lines with AQP8 knockdown and AQP8 rescue by CRISPR/Cas9 technology and overexpression of lentiviral vectors. We used CCK-8 and flow cytometry to test cell proliferation and cycle, immunofluorescence and Mito-Tracker CMXRos to observe the distribution of AQP8 expression in glioma cells, Amplex and DHE to study mitochondria release of H2O2, mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. Result: We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2O2 from mitochondria and led to increased levels of ROS in mitochondria, thereby impairing mitochondrial function. We also discovered that AQP8 knockdown resulted in suppression of cell proliferation and was blocked at the G0/G1 phase with increased expression of mitochondrial ROS signalling-related p53/p21. Conclusions: This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas.

基金机构： [cstc2014jcyjA10028]; [cstc2016jcyjA0229]

基金资助正文：The project was funded by ShuJuan Zhu [Grant ID: cstc2014jcyjA10028] and Jin Xu [Grant ID: cstc2016jcyjA0229].