Curcumin Attenuates Hydroxychloroquine-mediated Apoptosis and Oxidative Stress Via the Inhibition of TRPM2 Channel Signalling Pathways in a Retinal Pigment Epithelium Cell Line

Overview

Journal Graefes Arch Clin Exp Ophthalmol

Specialty Ophthalmology

Date 2023 Apr 26

PMID 37099129

Authors

Alper Ertugrul

Dilek Ozkaya

Mustafa Naziroglu

Affiliations

Soon will be listed here.

Abstract

Purpose: Hydroxychloroquine (HCQ) is used in the treatment of several diseases, such as malaria, Sjögren's disease, Covid-19, and rheumatoid arthritis. However, HCQ induces retinal pigment epithelium death via the excessive increase of cytosolic (cROS) and mitochondrial (mROS) free oxygen radical production. The transient receptor potential melastatin 2 (TRPM2) cation channel is stimulated by ADP-ribose (ADPR), cROS, and mROS, although it is inhibited by curcumin (CRC). We aimed to investigate the modulating action of CRC on HCQ-induced TRPM2 stimulation, cROS, mROS, apoptosis, and death in an adult retinal pigment epithelial 19 (ARPE19) cell line model.

Material And Methods: ARPE19 cells were divided into four groups: control (CNT), CRC (5 µM for 24 h), HCQ (60 µM for 48 h), and CRC + HCQ groups.

Results: The levels of cell death (propidium iodide positive cell numbers), apoptosis markers (caspases -3, -8, and -9), oxidative stress (cROS and mROS), mitochondria membrane depolarization, TRPM2 current density, and intracellular free Ca and Zn fluorescence intensity were upregulated in the HCQ group after stimulation with hydrogen peroxide and ADPR, but their levels were downregulated by treatments with CRC and TRPM2 blockers (ACA and carvacrol). The HCQ-induced decrease in retinal live cell count and cell viability was counteracted by treatment with CRC.

Conclusion: HCQ-mediated overload Ca influx and retinal oxidative toxicity were induced in an ARPE19 cell line through the stimulation of TRPM2, although they were attenuated by treatment with CRC. Hence, CRC may be a potential therapeutic antioxidant for TRPM2 activation and HCQ treatment-induced retinal oxidative injury and apoptosis.

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References

Dima A, Jurcut C, Arnaud L . Hydroxychloroquine in systemic and autoimmune diseases: Where are we now?. Joint Bone Spine. 2021; 88(3):105143. DOI: 10.1016/j.jbspin.2021.105143. View

Ferreira P, de Sousa R, Ferreira J, Militao G, Bezerra D . Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms. Pharmacol Res. 2021; 168:105582. DOI: 10.1016/j.phrs.2021.105582. View

Hsu S, Ponugoti A, Deaner J, Vajzovic L . Update on Retinal Drug Toxicities. Curr Ophthalmol Rep. 2021; 9(4):168-177. PMC: 8688906. DOI: 10.1007/s40135-021-00277-x. View

Doyno C, Sobieraj D, Baker W . Toxicity of chloroquine and hydroxychloroquine following therapeutic use or overdose. Clin Toxicol (Phila). 2020; 59(1):12-23. DOI: 10.1080/15563650.2020.1817479. View

Ding H, Denniston A, Rao V, Gordon C . Hydroxychloroquine-related retinal toxicity. Rheumatology (Oxford). 2015; 55(6):957-67. DOI: 10.1093/rheumatology/kev357. View

Korthagen N, Bastiaans J, van Meurs J, van Bilsen K, van Hagen P, Dik W . Chloroquine and Hydroxychloroquine Increase Retinal Pigment Epithelial Layer Permeability. J Biochem Mol Toxicol. 2015; 29(7):299-304. DOI: 10.1002/jbt.21696. View

Dhillon B, Singh S, Keifer J, Kumar U, Shaikh S, Ho S . Ameliorating hydroxychloroquine induced retinal toxicity through cerium oxide nanoparticle treatments. J Biomater Appl. 2021; 36(6):1033-1041. DOI: 10.1177/08853282211030150. View

Guzel M, Akpinar O . Hydroxychloroquine Attenuates Acute Inflammation (LPS)-Induced Apoptosis via Inhibiting TRPV1 Channel/ROS Signaling Pathways in Human Monocytes. Biology (Basel). 2021; 10(10). PMC: 8533250. DOI: 10.3390/biology10100967. View

Nguyen Hoang A, Lee H, Lee S . Casein kinase I inhibitor D4476 influences autophagy and apoptosis in chloroquine-induced adult retinal pigment epithelial-19 cells. Exp Eye Res. 2022; 218:109004. DOI: 10.1016/j.exer.2022.109004. View

10.

Yoon Y, Cho K, Hwang J, Lee S, Choi J, Koh J . Induction of lysosomal dilatation, arrested autophagy, and cell death by chloroquine in cultured ARPE-19 cells. Invest Ophthalmol Vis Sci. 2010; 51(11):6030-7. DOI: 10.1167/iovs.10-5278. View

11.

Ozkaya D, Naziroglu M . Bevacizumab induces oxidative cytotoxicity and apoptosis via TRPM2 channel activation in retinal pigment epithelial cells: Protective role of glutathione. Graefes Arch Clin Exp Ophthalmol. 2021; 259(6):1539-1554. DOI: 10.1007/s00417-021-05074-7. View

12.

Ozkaya D, Shu X, Naziroglu M . Deletion of Mitochondrial Translocator Protein (TSPO) Gene Decreases Oxidative Retinal Pigment Epithelial Cell Death via Modulation of TRPM2 Channel. Biology (Basel). 2021; 10(5). PMC: 8145237. DOI: 10.3390/biology10050382. View

13.

Ozkaya D, Naziroglu M, Vanyorek L, Muhamad S . Involvement of TRPM2 Channel on Hypoxia-Induced Oxidative Injury, Inflammation, and Cell Death in Retinal Pigment Epithelial Cells: Modulator Action of Selenium Nanoparticles. Biol Trace Elem Res. 2021; 199(4):1356-1369. DOI: 10.1007/s12011-020-02556-3. View

14.

Bhattacharyya S, Sturgis J, Maminishkis A, Miller S, Bonilha V . Oxidation of DJ-1 Cysteines in Retinal Pigment Epithelium Function. Int J Mol Sci. 2022; 23(17). PMC: 9456479. DOI: 10.3390/ijms23179938. View

15.

Ozkaya D, Naziroglu M . Curcumin diminishes cisplatin-induced apoptosis and mitochondrial oxidative stress through inhibition of TRPM2 channel signaling pathway in mouse optic nerve. J Recept Signal Transduct Res. 2020; 40(2):97-108. DOI: 10.1080/10799893.2020.1720240. View

16.

Daldal H, Naziroglu M . Carvacrol protects the ARPE19 retinal pigment epithelial cells against high glucose-induced oxidative stress, apoptosis, and inflammation by suppressing the TRPM2 channel signaling pathways. Graefes Arch Clin Exp Ophthalmol. 2022; 260(8):2567-2583. DOI: 10.1007/s00417-022-05731-5. View

17.

Naziroglu M . New molecular mechanisms on the activation of TRPM2 channels by oxidative stress and ADP-ribose. Neurochem Res. 2007; 32(11):1990-2001. DOI: 10.1007/s11064-007-9386-x. View

18.

Perraud A, Fleig A, Dunn C, Bagley L, Launay P, Schmitz C . ADP-ribose gating of the calcium-permeable LTRPC2 channel revealed by Nudix motif homology. Nature. 2001; 411(6837):595-9. DOI: 10.1038/35079100. View

19.

Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T . LTRPC2 Ca2+-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell. 2002; 9(1):163-73. DOI: 10.1016/s1097-2765(01)00438-5. View

20.

Naziroglu M, Luckhoff A . A calcium influx pathway regulated separately by oxidative stress and ADP-Ribose in TRPM2 channels: single channel events. Neurochem Res. 2008; 33(7):1256-62. DOI: 10.1007/s11064-007-9577-5. View