Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells
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Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investi- gated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the in- tracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, fol- lowed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.
Abstract
Based on the reactive oxygen species (ROS) regulatory properties of diphenyleneiodonium (DPI), we investi- gated the effects of DPI on host-infected T. gondii proliferation and determined specific concentration that inhibit the in- tracellular parasite growth but without severe toxic effect on human retinal pigment epithelial (ARPE-19) cells. As a result, it is observed that host superoxide, mitochondria superoxide and H2O2 levels can be increased by DPI, significantly, fol- lowed by suppression of T. gondii infection and proliferation. The involvement of ROS in anti-parasitic effect of DPI was confirmed by finding that DPI effect on T. gondii can be reversed by ROS scavengers, N-acetyl-L-cysteine and ascorbic acid. These results suggest that, in ARPE-19 cell, DPI can enhance host ROS generation to prevent T. gondii growth. Our study showed DPI is capable of suppressing T. gondii growth in host cells while minimizing the un-favorite side-effect to host cell. These results imply that DPI as a promising candidate material for novel drug development that can ameliorate toxoplasmosis based on ROS regulation.
참고문헌 (17)
- Tenter AM, "Toxoplasma gondii : from animals to humans", Int J Parasitol, 30, pp.1217~1258 (2000)
- Young-Hoon Park, "Clinical Features and Treatment of Ocular Toxoplasmosis", Parasites, Hosts and Diseases, 51(4), pp.393~399 (2013), 대한기생충학ㆍ열대의학회
- Cai J, "Oxidative damage and protection of the RPE", Prog Retin Eye Res, 19, pp.205~221 (2000)
- Espinosa A, "Reactive oxygen species and calcium signals in skeletal muscle : a crosstalk involved in both normal signaling and disease", Cell Calcium, 60, pp.172~179 (2016)
- Birben E, "Oxidative stress and antioxidant defense", World Allergy Organ J, 5, pp.9~19 (2012)
- Woods JR Jr, "An introduction to reactive oxygen species and their possible roles in substance abuse", Obstet Gynecol Clin North Am, 25, pp.219~236 (1998)
- Massart C, "Diphenyleneiodonium, an inhibitor of NOXes and DUOXes, is also an iodide-specific transporter", FEBS Open Bio, 4, pp.55~59 (2013)
- Szilagyi JT, "Selective targeting of heme protein in cytochrome P450 and nitric oxide synthase by diphenyleneiodonium", Toxicol Sci, 151, pp.150~159 (2016)
- Sharma M, "Diphenyleneiodonium enhances oxidative stress and inhibits Japanese encephalitis virus induced autophagy and ER stress pathways", Biochem Biophys Res Commun, 502, pp.232~237 (2018)
- Wei Zhou, "Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K", Akt or mTOR Signal Pathway, 2018, pp.56(2), 135~145[DOI]
- Kučera J, "Apocynin and diphenyleneiodonium induce oxidative stress and modulate PI3K", Akt and MAPK, Oxid Med Cell Longev, pp.2016, 2016[DOI]
- Li N, "DPI induces mitochondrial superoxide-mediated apoptosis", Free Radic Biol Med, 34, pp.465~477 (2003)
- Clough B, "K63-linked ubiquitination targets Toxoplasma gondii for endo-lysosomal destruction in IFNγ-stimulated human cells", PLoS Pathog, 12, pp.e1006027~ (2016)
- Li Y, "Diphenyleneiodonium, an NAD(P)H oxidase inhibitor, also potently inhibits mitochondrial reactive oxygen species production", Biochem Biophys Res Commun, 253, pp.295~299 (1998)
- Park SE, "Diphenyleneiodonium induces ROS-independent p53 expression and apoptosis in human RPE cells", FEBS Lett, 581, pp.180~186 (2007)
- Riganti C, "Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress", J Biol Chem, 279, pp.47726~47731 (2004)
- Stowe DF, "Mitochondrial reactive oxygen species production in excitable cells : modulators of mitochondrial and cell function", Antioxid Redox Signal, 11, pp.1373~1414 (2009)
