Fig. 5.

Summary of cross talk between OGD-induced Zn²⁺ and ROS increases that involve intracellular Zn²⁺ storage, mitochondria, and NADPH oxidase. A: schematic drawing of intracellular Zn²⁺ storage including metallothioneins (MT), organelle apparatus such as endoplasmic reticulum, and mitochondria, showing the release and uptake of Zn²⁺ by them in four described phases of Zn²⁺ rises during OGD. B: diagram of temporal relationship of OGD-induced Zn²⁺ and ROS accumulation during the course of prolonged hypoxic exposure (30 min in the present study). Green area represents Zn²⁺ increases; red line shows ROS accumulation. Roman numerals and vertical dashed lines show four phases of Zn²⁺ transient during OGD. C: schematic drawing showing mitochondrial Zn²⁺ storage and release during OGD in relationship with mitochondrial ROS production and NADPH oxidase-mediated ROS production. C,a: before OGD. C,b: mitochondria uptake and store Zn²⁺ during OGD. Drawing shows the positive feedback between mitochondrial Zn²⁺ stress facilitating ROS production, which further releases Zn²⁺. C,c: the large release of Zn²⁺ and ROS from mitochondria. Zn²⁺ may activate NADPH oxidase and consequently further increase ROS accumulation.