Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 Apr;199(4):1356-1369.
doi: 10.1007/s12011-020-02556-3. Epub 2021 Jan 2.

Involvement of TRPM2 Channel on Hypoxia-Induced Oxidative Injury, Inflammation, and Cell Death in Retinal Pigment Epithelial Cells: Modulator Action of Selenium Nanoparticles

Dilek Özkaya  1 , Mustafa Nazıroğlu  2   3   4 , László Vanyorek  5 , Salina Muhamad  6
Affiliations

Involvement of TRPM2 Channel on Hypoxia-Induced Oxidative Injury, Inflammation, and Cell Death in Retinal Pigment Epithelial Cells: Modulator Action of Selenium Nanoparticles

Dilek Özkaya et al. Biol Trace Elem Res. 2021 Apr.

Abstract

Hypoxia (HYPX) in several eye diseases such as glaucoma and diabetic retinopathy causes oxidative cell death and inflammation. TRPM2 cation channel is activated by HYPX-induced ADP-ribose (ADPR) and oxidative stress. The protective role of selenium via inhibition of TRPM2 on the HYPX-induced oxidative cytotoxicity and inflammation values in the human kidney cell line was recently reported. However, the protective role of selenium nanoparticles (SeNP) on the values in the retinal pigment epithelial (ARPE-19) cells has not been clarified yet. In the current study, we investigated two subjects. First, we investigated the involvement of TRPM2 channel on the HYPX-induced oxidative injury, inflammation, and apoptosis in the ARPE-19 cells. Second, we investigated the protective role of SeNP via inhibition of TRPM2 channel on the HYPX-induced oxidative injury and apoptosis in the ARPE-19 cells. For the aims, the ARPE-19 cells were divided into four main groups as follows: Control (Ctr), SeNP (2.5 μg/ml for 24 h), HYPX (200 μM CoCl2 for 24 h), and HYPX+SeNP. The TRPM2 current density and Ca2+ fluorescence intensity with an increase of mitochondrial membrane depolarization and oxygen free radical (OFR) generations were increased in the ARPE-19 cells by the treatment of HYPX. There was no increase of Ca2+ fluorescence intensity in the pre-treated cells with PARP-1 inhibitors (DPQ and PJ34) or in the presence of Ca2+-free extracellular buffer. When HYPX-induced TRPM2 activity was treated by SeNP and TRPM2 (2-APB and ACA) blockers, the increases of OFR generation, cytokine (TNF-α and IL-1β) levels, TRPM2, and PARP-1 expressions were restored. In conclusion, the exposure of HYPX caused mitochondrial oxidative cell cytotoxicity and cell death via TRPM2-mediated Ca2+ signaling and may provide an avenue for treating HYPX-induced retinal diseases associated with the excessive OFR and Ca2+ influx.

Keywords: Hypoxia; Inflammation; Oxidative cytotoxicity; PARP-1; Retinal pigment epithelial cells; Selenium nanoparticles.

PubMed Disclaimer

References

    1. Masuda T, Shimazawa M, Hara H (2017) Retinal diseases associated with oxidative stress and the effects of a free radical scavenger (Edaravone). Oxidative Med Cell Longev 2017:9208489–9208414. https://doi.org/10.1155/2017/9208489 - DOI
    1. Al-Kharashi AS (2018) Role of oxidative stress, inflammation, hypoxia and angiogenesis in the development of diabetic retinopathy. Saudi J Ophthalmol 32(4):318–323. https://doi.org/10.1016/j.sjopt.2018.05.002 - DOI - PubMed - PMC
    1. Kovacs K, Vaczy A, Fekete K, Kovari P, Atlasz T, Reglodi D, Gabriel R, Gallyas F, Sumegi B (2019) PARP inhibitor protects against chronic hypoxia/reoxygenation-induced retinal injury by regulation of MAPKs, HIF1α, Nrf2, and NFκB. Invest Ophthalmol Vis Sci 60(5):1478–1490. https://doi.org/10.1167/iovs.18-25936 - DOI - PubMed
    1. Ren L, Tao J, Chen H, Bian Y, Yang X, Chen G, Zhang X, Liang G, Wu W, Song Z, Wang Y (2017) Myeloid differentiation protein 2-dependent mechanisms in retinal ischemia-reperfusion injury. Toxicol Appl Pharmacol 317:1–11. https://doi.org/10.1016/j.taap.2017.01.001 - DOI - PubMed
    1. Gorbatyuk MS, Starr CR, Gorbatyuk OS (2020, 2020) Endoplasmic reticulum stress: new insights into the pathogenesis and treatment of retinal degenerative diseases. Prog Retin Eye Res 6:100860. https://doi.org/10.1016/j.preteyeres.2020.100860

LinkOut - more resources