GPx-1-encoded adenoviral vector attenuates dopaminergic impairments induced by methamphetamine in GPx-1 knockout mice through modulation of NF-κB transcription factor.

Autor: Sharma N; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea., Shin EJ; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea., Pham DT; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea., Sharma G; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea., Dang DK; Pharmacy Faculty, Can Tho University of Medicine and Pharmacy, Can Tho City, 900000, Viet Nam., Duong CX; Pharmacy Faculty, Can Tho University of Medicine and Pharmacy, Can Tho City, 900000, Viet Nam., Kang SW; Department of Life Science, College of Natural Science, Ewha Womans University, Seoul, 03760, Republic of Korea., Nah SY; Ginsentology Research Laboratory and Department of Physiology, College of Veterinary Medicine and Bio/Molecular Informatics Center, Konkuk University, Seoul, 05029, Republic of Korea., Jang CG; Department of Pharmacology, School of Pharmacy, Sungkyunkwan University, Suwon, 440-746, Republic of Korea., Lei XG; Department of Animal Science, Cornell University, Ithaca, NY, 14853, USA., Nabeshima T; Advanced Diagnostic System Research Laboratory, Fujita Health University Graduate School of Health Science, Toyoake, 470-1192, Japan., Bing G; Anatomy and Neurobiology, University of Kentucky Medical Center, Medical Center MN208 800 Rose Strees, Lexington, KY, 40536, USA., Jeong JH; Department of Global Innovative Drugs, Graduate School of Chung-Ang University, College of Medicine, Chung-Ang University, Seoul, 06974, Republic of Korea. Electronic address: jhjeong3@cau.ac.kr., Kim HC; Neuropsychopharmacology and Toxicology Program, College of Pharmacy, Kangwon National University, Chunchon, 24341, South Korea. Electronic address: kimhc@kangwon.ac.kr.
Jazyk: angličtina
Zdroj: Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association [Food Chem Toxicol] 2021 Aug; Vol. 154, pp. 112313. Date of Electronic Publication: 2021 Jun 01.
DOI: 10.1016/j.fct.2021.112313
Abstrakt: We suggested that selenium-dependent glutathione peroxidase (GPx) plays a protective role against methamphetamine (MA)-induced dopaminergic toxicity. We focused on GPx-1, a major selenium-dependent enzyme and constructed a GPx-1 gene-encoded adenoviral vector (Ad-GPx-1) to delineate the role of GPx-1 in MA-induced dopaminergic neurotoxicity. Exposure to Ad-GPx-1 significantly induced GPx activity and GPx-1 protein levels in GPx-1-knockout (GPx-1-KO) mice. MA-induced dopaminergic impairments [i.e., hyperthermia; increased nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) DNA-binding activity; and decreased dopamine levels, TH activity, and behavioral activity] were more pronounced in GPx-1-KO mice than in WT mice. In contrast, exposure to Ad-GPx-1 significantly attenuated MA-induced dopaminergic loss in GPx-1-KO mice. The protective effect exerted by Ad-GPx-1 was comparable to that exerted by pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor against MA insult. Consistently, GPx-1 overexpression significantly attenuated MA dopaminergic toxicity in mice. PDTC did not significantly impact the protective effect of GPx-1 overexpression, suggesting that interaction between NF-κB and GPx-1 is critical for dopaminergic protection. Thus, NF-κB is a potential therapeutic target for GPx-1-mediated dopaminergic protective activity. This study for the first time demonstrated that Ad-GPx-1 rescued dopaminergic toxicity in vivo following MA insult. Furthermore, GPx-1-associated therapeutic interventions may be important against dopaminergic toxicity.
(Copyright © 2021 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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