Deletion of mitochondrial translocator protein (Tspo) gene decreases oxidative retinal pigment epithelial cell death via modulation of trpm2 channel

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Abstract

The current results indicated the possible protective actions of 18 kDa mitochondrial translocator protein (TSPO) deletion on TRPM2 stimulation, mitochondrial free ROS (Mito-fROS) and apoptotic harmful actions in the cells of adult retinal pigment epithelial19 (ARPE19). There was a direct relationship between TSPO and the disease of age-related macular degeneration. The nature of TSPO implicates upregulation of Mito-fROS and apoptosis via the activation of Ca2+ channels in ARPE19, although deletion of TSPO gene downregulates the activation. The decrease of oxidative cytotoxicity and apoptosis might induce in TSPO gene deleted cells by the inhibition of Mito-fROS and PARP-1 activation-induced TRPM2 cation channel activation. The ARPE19 cells were divided into two main groups as TSPO expressing (ARPE19) and non-expressing cells (ARPE19-KO). The levels of caspase-3 (Casp-3), caspase-9 (Casp-9), apoptosis, Mito-fROS, TRPM2 current and intracellular free Ca2+ were upregulated in the ARPE19 by the stimulations of H2O2 and ADP-ribose, although their levels were downregulated in the cells by the modulators of PARP-1 (DPQ and PJ34), TRPM2 (ACA and 2APB) and glutathione. However, the H2O2 and ADP-ribose-mediated increases were not observed in the ARPE19-KO. The expression levels of Bax, Casp-3, Casp-9 and PARP-1 were higher in the ARPE19 group as compared to the ARPE19-KO group. In summary, current results confirmed that TRPM2-mediated cell death and oxidative cytotoxicity in the ARPE19 cells were occurred by the presence of TSPO. The deletion of TSPO may be considered as a therapeutic way to TRPM2 activation-mediated retinal oxidative injury.

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Özkaya, D., Shu, X., & Nazıroğlu, M. (2021). Deletion of mitochondrial translocator protein (Tspo) gene decreases oxidative retinal pigment epithelial cell death via modulation of trpm2 channel. Biology, 10(5). https://doi.org/10.3390/biology10050382

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