1. AQP8 Modulates Mitochondrial H2O2 Transport to Influence Glioma Proliferation.
- Author
-
Shen, ZiHao, Sheng, HuaJun, Zhao, Jing, Xu, Jin, Cai, ZiLing, Zhang, Hao, Guo, Zhen, Liu, JunNan, Liang, Hang, Tan, LiHao, Gan, ShengWei, Huang, Juan, and Zhu, ShuJuan
- Subjects
BRAIN tumor genetics ,FLOW cytometry ,GLIOMAS ,MITOCHONDRIA ,RESEARCH funding ,CELL proliferation ,CELLULAR signal transduction ,FLUORESCENT antibody technique ,DESCRIPTIVE statistics ,REACTIVE oxygen species ,CELL lines ,GENES ,GASTROINTESTINAL hormones ,MEMBRANE potential ,HYDROGEN peroxide ,TECHNOLOGY ,BRAIN tumors ,MEMBRANE proteins - Abstract
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 H
2 O2 , 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. 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 H2 O2 , mitochondrial membrane potential (MMP) and NAD+/NADH ratio to assess mitochondrial function and protein blotting to detect p53 and p21 expression. We found that AQP8 co-localised with mitochondria and that knockdown of AQP8 inhibited the release of H2 O2 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. This finding provides further evidence for mechanistic studies of AQP8 as a prospective target for the treatment of gliomas. [ABSTRACT FROM AUTHOR]- Published
- 2024
- Full Text
- View/download PDF