Dephosphorylation of ERK1/2 and DRP1 S585 regulates mitochondrial dynamics in glutamate toxicity of retinal neurons in vitro. (December 2022)

• Record Type: Journal Article
• Authors: Zeng, Zhou; Li, Haibo; You, Mengling; Rong, Rong; Xia, Xiaobo
• Is Part Of: Experimental eye research. Volume 225(2022)
• Publication Date: 2022-12
• Subjects: Glaucoma -- Glutamate excitatory toxicity -- Mitochondrial dynamics -- Retinal neurons -- DRP1; Ophthalmology -- Periodicals; Eye -- Periodicals; Œil -- Périodiques; Ophthalmology; Periodicals; Electronic journals; 612.8405
• DOI: 10.1016/j.exer.2022.109271
• Languages: English
• ISSNs: 0014-4835

Abstract

Abstract: There are many theories surrounding the pathogenesis of glaucoma, and glutamate excitatory toxicity has been suggested to play an important role. Some studies have shown that glutamate excitatory toxicity is associated with mitochondrial dynamics; however, the relationship between glutamate excitatory toxicity and mitochondrial dynamics in the pathogenesis of glaucoma remains unclear. In this study, the glutamate transporter inhibitor, threohydroxyaspartate, was used to simulate the glutamate excitatory toxicity cell model of rat retinal neurons in vitro, and the changes in the level of proteins related to mitochondrial dynamics, mitochondrial morphology, and length of neuronal axons were measured. We found that in the glutamate excitotoxicity model, retinal neurons can promote mitochondrial fusion by reducing the phosphorylation of ERK1/2 and its downstream protein DRP1 S585, and enhance its ability to resist the excitotoxicity of glutamate. At the same time, the DRP1-specific inhibitor, Mdivi-1, could promote the mitochondrial fusion of retinal neurons. Highlights: THA induces glutamate excitatory toxicity model of retinal neurons in vitro was successfully established. In retinal neurons, THA down-regulates the phosphoylation levels of ERK1/2 and DRP1serine 585. THA increased mitochondrial fusion in retinal neurons, thereby initiating compensatory neuroprotective effects. Mdivi-1 protects retinal neurons by downregulating the phosphorylation level of DRP1 serine 585.