본문 바로가기
KERD
논문KCI 등재

Dipenyleneiodonium Induces Growth Inhibition of Toxoplasma gondii through ROS Induction in ARPE-19 Cells

2

조회

0

다운로드

0

인용

0

참고문헌

키워드

초록

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)

  1. Tenter AM, "Toxoplasma gondii : from animals to humans", Int J Parasitol, 30, pp.1217~1258 (2000)
  2. Young-Hoon Park, "Clinical Features and Treatment of Ocular Toxoplasmosis", Parasites, Hosts and Diseases, 51(4), pp.393~399 (2013), 대한기생충학ㆍ열대의학회
  3. Cai J, "Oxidative damage and protection of the RPE", Prog Retin Eye Res, 19, pp.205~221 (2000)
  4. 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)
  5. Birben E, "Oxidative stress and antioxidant defense", World Allergy Organ J, 5, pp.9~19 (2012)
  6. 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)
  7. Massart C, "Diphenyleneiodonium, an inhibitor of NOXes and DUOXes, is also an iodide-specific transporter", FEBS Open Bio, 4, pp.55~59 (2013)
  8. Szilagyi JT, "Selective targeting of heme protein in cytochrome P450 and nitric oxide synthase by diphenyleneiodonium", Toxicol Sci, 151, pp.150~159 (2016)
  9. 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)
  10. 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]
  11. Kučera J, "Apocynin and diphenyleneiodonium induce oxidative stress and modulate PI3K", Akt and MAPK, Oxid Med Cell Longev, pp.2016, 2016[DOI]
  12. Li N, "DPI induces mitochondrial superoxide-mediated apoptosis", Free Radic Biol Med, 34, pp.465~477 (2003)
  13. Clough B, "K63-linked ubiquitination targets Toxoplasma gondii for endo-lysosomal destruction in IFNγ-stimulated human cells", PLoS Pathog, 12, pp.e1006027~ (2016)
  14. 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)
  15. Park SE, "Diphenyleneiodonium induces ROS-independent p53 expression and apoptosis in human RPE cells", FEBS Lett, 581, pp.180~186 (2007)
  16. Riganti C, "Diphenyleneiodonium inhibits the cell redox metabolism and induces oxidative stress", J Biol Chem, 279, pp.47726~47731 (2004)
  17. Stowe DF, "Mitochondrial reactive oxygen species production in excitable cells : modulators of mitochondrial and cell function", Antioxid Redox Signal, 11, pp.1373~1414 (2009)

관련 논문AI추천

The Role of PI3K/AKT Pathway and NADPH Oxidase 4 in Host ROS Manipulation by Toxoplasma gondii육재민, 이영하, 차광호, GAOFEIFEI, Hei Gwon Choi, Pu-Reum Sun, Wei Zhou대한기생충학ㆍ열대의학회 · Parasites, Hosts and Diseases2020 · 제58권 제3호Modulated Gene Expression of Toxoplasma gondii Infected Retinal Pigment Epithelial Cell Line (ARPE-19) via PI3K/Akt or mTOR Signal Pathway이영하, 차광호, GAOFEIFEI, Hassan Ahmed Hassan Ahmed Ismail, Juan-Hua Quan, Wei Zhou대한기생충학ㆍ열대의학회 · Parasites, Hosts and Diseases2018 · 제56권 제2호In Vitro and in Vivo Effects of Nitrofurantoin on Experimental ToxoplasmosisChunMei Jin, Hyun Park, Seon-Ju Yeo, SungYeon Kim대한기생충학ㆍ열대의학회 · Parasites, Hosts and Diseases2016 · 제54권 제2호Suppressors for Human Epidermal Growth Factor Receptor 2/4 (HER2/4): A New Family of Anti-Toxoplasmic Agents in ARPE-19 Cells김영훈, 남호우, 안혜진, 이원규, Lokraj Bhatt, Zhaoshou Yang대한기생충학ㆍ열대의학회 · Parasites, Hosts and Diseases2017 · 제55권 제5호In Vitro Activity of Diphenyleneiodonium toward Multidrug-Resistant Helicobacter pylori Strains김수영, 김인기, 박장호, 박희정, 이선미, 이진혁, 이희우, 정준원, 정진용, 청장수거트앤리버 소화기연관학회협의회 · Gut and Liver2017 · 제11권 제5호Diphenyleneiodonium Inhibits Apoptotic Cell Death of Gastric Epithelial Cells Infected with Helicobacter pylori in a Korean Isolate김혜영, 임주원, 조순옥연세대학교의과대학 · Yonsei Medical Journal2015 · 제56권 제4호

이 간행물의 다른 논문 (16건)