MCT2激活Nrf2通路调控H/R视网膜神经节细胞凋亡与焦亡

doi:10.3969/j.issn.1006-6233.2022.09.04

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Abstract Objective: To explore the effect and mechanism of monocarboxylate transporters 2 (MCT2) on apoptosis and pyrolysis of retinal ganglion cells after hypoxia/reoxygenation (H/R). Methods: Retinal ganglion cells RGC-5 were randomly divided into control group, H/R group, MCT2 group, MCT2+ML385 group, and pcDNA3.1-MCT2 recombinant plasmid was transfected into RGC-5 cells via liposome to establish Cell H/R model, and treat cells with Nrf2 inhibitor ML385. After the cells were treated accordingly, transfection efficiency was measured by real-time fluorescence quantitative PCR and protein blotting (Western blot), cell proliferation activity was measured by CCK-8, apoptosis level was measured by flow cytometry, PI apoptosis index was measured by Hoechst/PI staining, expression levels of apoptosis-related and pyrolysis-related proteins were measured by Western blot, and expression of Nrf2 and Caspase-1 were observed by immunofluorescence staining. Results: After transfection of pcDNA3.1-MCT2 into RGC-5 cells, both intracellular MCT2 mRNA and protein relative expression were significantly upregulated (P<0.05); after H/R treatment, cell proliferation activity decreased, apoptosis rate increased, PI apoptosis index increased, intracellular Bax and Caspase-3 protein relative expression were both upregulated while Bcl-2 protein relative The relative expression of Bax and Caspase-3 proteins was upregulated while that of Bcl-2 protein was downregulated, the relative expression of GSDMD, Caspase-1, NLRP3, and IL-1β proteins were upregulated, the fluorescence intensity of Nrf2 was reduced and that of Caspase-1 was enhanced. After transfected with pcDNA3.1-MCT2 and then treated with H/R, cell proliferation activity increased, apoptosis rate decreased, PI apoptosis index decreased, relative expression of intracellular Bax and Caspase-3 proteins were down-regulated, relative expression of Bcl-2 protein was up-regulated. The relative expression of GSDMD, Caspase-1, NLRP3, and IL-1β were all down-regulated, the fluorescence intensity of Nrf2 was enhanced and that of Caspase-1 was diminished, all differences were statistically significant (P<0.05); while cells treated with transfected pcDNA3.1-MCT2 with H/R followed by Nrf2 inhibitor ML385 showed a decrease in cell proliferation activity, an increase in apoptosis rate and PI apoptosis index, intracellular Bax and Caspase-3 protein relative expression was upregulated, Bcl-2 protein relative expression was downregulated, GSDMD, Caspase-1, NLRP3, and IL-1β protein relative expression was upregulated, Nrf2 fluorescence intensity was diminished and Caspase-1 fluorescence intensity was enhanced, all differences were statistically significant (P<0.05). Conclusion: MCT2 inhibits H/R-induced apoptosis and focal death in retinal ganglion cells, and this mechanism of action may be related to the activation of the Nrf2 pathway.

Key words： Monocarboxylic acid transporter 2 Retinal ganglion cells Apoptosis Pyrolysis Nuclear factor E2 related factors

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	ZHANG Xiaomin
	LIU Wen
	CAI Aozhu

Cite this article:

ZHANG Xiaomin,LIU Wen,CAI Aozhu. Activation of the Nrf2 Pathway by MCT2 Regulates Apoptosis and Pyroptosis in H/R Retinal Ganglion Cells[J]. HeBei Med, 2022, 28(9): 1425-1430.

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http://www.hbyxzzs.cn/EN/10.3969/j.issn.1006-6233.2022.09.04 OR http://www.hbyxzzs.cn/EN/Y2022/V28/I9/1425

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