Deletion of Mitochondrial Translocator Protein (TSPO) gene decreases oxidative retinal pigment epithelial cell death via modulation of TRPM2 channel

Dilek Özkaya, Xinhua Shu, Mustafa Nazıroğlu*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Downloads (Pure)

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.
Original languageEnglish
Article number382
Number of pages18
JournalBiology
Volume10
Issue number5
DOIs
Publication statusPublished - 28 Apr 2021

Keywords

  • ARPE19 cells; cell death; mitochondrial translocator protein; mitochondrial oxidative cytotoxicity; TRPM2 channel

Fingerprint

Dive into the research topics of 'Deletion of Mitochondrial Translocator Protein (TSPO) gene decreases oxidative retinal pigment epithelial cell death via modulation of TRPM2 channel'. Together they form a unique fingerprint.

Cite this