دورية أكاديمية
Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity.
| العنوان: | Thimerosal inhibits Drosophila melanogaster tyrosine hydroxylase (DmTyrH) leading to changes in dopamine levels and impaired motor behavior: implications for neurotoxicity. |
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| المؤلفون: | Bianchini MC; Universidade Federal do Pampa - Campus Uruguaiana, Programa de Pós-Graduação em Bioquímica (PPGBioq), BR-472 Km 7, CEP 97500-970, Uruguaiana, RS, Brazil. robson_puntel@yahoo.com.br., Gularte COA, Nogara PA, Krum BN, Gayer MC, Bridi JC, Roos DH, Roehrs R, Fachinetto R, Pinton S, Ávila DS, Hirth F, Rocha JBT, Puntel RL |
| المصدر: | Metallomics : integrated biometal science [Metallomics] 2019 Feb 20; Vol. 11 (2), pp. 362-374. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Oxford University Press Country of Publication: England NLM ID: 101478346 Publication Model: Print Cited Medium: Internet ISSN: 1756-591X (Electronic) Linking ISSN: 17565901 NLM ISO Abbreviation: Metallomics Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: 2021- : [Oxford] : Oxford University Press Original Publication: Cambridge : RSC Publishing, c2009- |
| مواضيع طبية MeSH: | Dopamine/*metabolism , Thimerosal/*pharmacology , Tyrosine 3-Monooxygenase/*metabolism, Animals ; Drosophila melanogaster ; Female ; Glutathione Transferase/metabolism ; Male ; Thiobarbituric Acid Reactive Substances/metabolism ; Thioredoxin-Disulfide Reductase/metabolism |
| مستخلص: | Thimerosal (THIM) is a well-established antifungal and antiseptic agent widely used as a preservative in vaccines. Recent studies identified the neurotoxic effects of THIM, including malfunction of the monoaminergic system. However, the underlying cytotoxic mechanisms are not well understood. Here we used the fruit fly Drosophila melanogaster to investigate the mechanisms of THIM-induced neurotoxicity. We focused on the dopaminergic system, and the rate-limiting enzyme tyrosine hydroxylase (DmTyrH), to test the hypothesis that THIM can impair dopamine (DA) homeostasis and subsequently cause dysfunction. We studied the effect of THIM by feeding 1-2 day old flies (both sexes) food supplemented with 25 μM THIM for 4 days and determined THIM-induced effects on survival, oxidative stress, and metabolic activity based on MTT assay and acetylcholinesterase (AChE) activity. Our results demonstrate that D. melanogaster exposed to THIM present changes in DmTyrH expression and activity, together with altered DA levels that led to impaired motor behavior. These phenotypes were accompanied by an increase in oxidative stress, with a decrease in MTT reduction, in AChE activity, and also in survival rate. These findings suggest an initiating and primary role for THIM-mediated DmTyrH dysfunction that leads to impaired DA function and behavioral abnormalities, ultimately causing oxidative stress-related neurotoxicity. |
| معلومات مُعتمدة: | HIRTH/OCT13/868-792 United Kingdom MNDA_ Motor Neurone Disease Association; G-0714 United Kingdom PUK_ Parkinson's UK; HIRTH/OCT16/890-792 United Kingdom MNDA_ Motor Neurone Disease Association; G0701498 United Kingdom MRC_ Medical Research Council; MR/L010666/1 United Kingdom MRC_ Medical Research Council; BB/N001230/1 United Kingdom BB_ Biotechnology and Biological Sciences Research Council |
| المشرفين على المادة: | 0 (Thiobarbituric Acid Reactive Substances) 2225PI3MOV (Thimerosal) EC 1.14.16.2 (Tyrosine 3-Monooxygenase) EC 1.8.1.9 (Thioredoxin-Disulfide Reductase) EC 2.5.1.18 (Glutathione Transferase) VTD58H1Z2X (Dopamine) |
| تواريخ الأحداث: | Date Created: 20181206 Date Completed: 20200504 Latest Revision: 20210109 |
| رمز التحديث: | 20231215 |
| DOI: | 10.1039/c8mt00268a |
| PMID: | 30516209 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1756-591X |
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| DOI: | 10.1039/c8mt00268a |