GPx-1-encoded adenoviral vector attenuates dopaminergic impairments induced by methamphetamine in GPx-1 knockout mice through modulation of NF-KB transcription factor
- 주제(키워드) GPx-1 gene-encoded adenoviral vector , GPx-1 knockout mice , GPx-1 overexpressing transgenic mice , NF-KB inhibitor , Striatum , Methamphetamine-induced dopaminergic  , toxicity
- 주제(기타) Food Science & Technology
- 주제(기타) Toxicology
- 설명문(일반) [Sharma, Naveen; Shin, Eun-Joo; Duc Toan Pham; Sharma, Garima; Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 24341, South Korea; [Sharma, Naveen; Jeong, Ji Hoon] Chung Ang Univ, Grad Sch, Coll Med, Dept Global Innovat Drugs, Seoul 06974, South Korea; [Duy-Khanh Dang; Chu Xuan Duong] Can Tho Univ Med & Pharm, Pharm Fac, Can Tho City 900000, Vietnam; [Kang, Sang Won] Ewha Womans Univ, Coll Nat Sci, Dept Life Sci, Seoul 03760, South Korea; [Nah, Seung-Yeol] Konkuk Univ, Coll Vet Med, Ginsentol Res Lab, Seoul 05029, South Korea; [Nah, Seung-Yeol] Konkuk Univ, Coll Vet Med, Dept Physiol, Seoul 05029, South Korea; [Nah, Seung-Yeol] Konkuk Univ, Bio Mol Informat Ctr, Seoul 05029, South Korea; [Jang, Choon-Gon] Sungkyunkwan Univ, Sch Pharm, Dept Pharmacol, Suwon 440746, South Korea; [Lei, Xin Gen] Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA; [Nabeshima, Toshitaka] Fujita Hlth Univ, Adv Diagnost Syst Res Lab, Grad Sch Hlth Sci, Toyoake, Aichi 4701192, Japan; [Bing, Guoying] Univ Kentucky, Med Ctr, Anat & Neurobiol, MN208 800 Rose Strees, Lexington, KY 40536 USA
- 등재 SCIE, SCOPUS
- 발행기관 PERGAMON-ELSEVIER SCIENCE LTD
- 발행년도 2021
- 총서유형 Journal
- URI http://www.dcollection.net/handler/ewha/000000182325
- 본문언어 영어
- Published As http://dx.doi.org/10.1016/j.fct.2021.112313
초록/요약
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-KB) 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-KB 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-KB and GPx-1 is critical for dopaminergic protection. Thus, NF-KB 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-1associated therapeutic interventions may be important against dopaminergic toxicity.
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