Signalling mechanisms mediating Zn²⁺-induced TRPM2 channel activation and cell death in microglial cells.

ABSTRACT: Excessive Zn²⁺ causes brain damage via promoting ROS generation. Here we investigated the role of ROS-sensitive TRPM2 channel in H₂O₂/Zn²⁺-induced Ca²⁺ signalling and cell death in microglial cells. H₂O₂/Zn²⁺ induced concentration-dependent increases in cytosolic Ca²⁺ concentration ([Ca²⁺]_c), which was inhibited by PJ34, a PARP inhibitor, and abolished by TRPM2 knockout (TRPM2-KO). Pathological concentrations of H₂O₂/Zn²⁺ induced substantial cell death that was inhibited by PJ34 and DPQ, PARP inhibitors, 2-APB, a TRPM2 channel inhibitor, and prevented by TRPM2-KO. Further analysis indicate that Zn²⁺ induced ROS production, PARP

SUBMITTER: Mortadza SS 

PROVIDER: S-EPMC5359577 | biostudies-literature | 2017 Mar

REPOSITORIES: biostudies-literature