Academic Journal
New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish
العنوان: | New insights into organ-specific oxidative stress mechanisms using a novel biosensor zebrafish |
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المؤلفون: | Mourabit, S, Fitzgerald, JA, Ellis, RP, Takesono, A, Porteus, CS, Trznadel, M, Metz, J, Winter, MJ, Kudoh, T, Tyler, CR |
بيانات النشر: | Elsevier |
سنة النشر: | 2019 |
المجموعة: | University of Exeter: Open Research Exeter (ORE) |
مصطلحات موضوعية: | Oxidative stress, Zebrafish, Toxicants, Biosensor |
الوصف: | This is the final version. Available from Elsevier via the DOI in this record. ; Background: Reactive oxygen species (ROS) arise as a result from, and are essential in, numerous cellular processes. ROS, however, are highly reactive and if left unneutralised by endogenous antioxidant systems, can result in extensive cellular damage and/or pathogenesis. In addition, exposure to a wide range of environmental stressors can also result in surplus ROS production leading to oxidative stress (OS) and downstream tissue toxicity. Objectives: Our aim was to produce a stable transgenic zebrafish line, unrestricted by tissue-specific gene regulation, which was capable of providing a whole organismal, real-time read-out of tissue-specific OS following exposure to a wide range of OS-inducing environmental contaminants and conditions. This model could, therefore, serve as a sensitive and specific mechanistic in vivo biomarker for all environmental conditions that result in OS. Methods: To achieve this aim, we exploited the pivotal role of the electrophile response element (EpRE) as a globally-acting master regulator of the cellular response to OS. To test tissue specificity and quantitative capacity, we selected a range of chemical contaminants known to induce OS in specific organs or tissues, and assessed dose-responsiveness in each using microscopic measures of mCherry fluorescence intensity. Results: We produced the first stable transgenic zebrafish line Tg (3EpRE:hsp70:mCherry) with high sensitivity for the detection of cellular RedOx imbalances, in vivo in near-real time. We applied this new model to quantify OS after exposure to a range of environmental conditions with high resolution and provided quantification both of compound- and tissue-specific ROS-induced toxicity. Discussion: Our model has an extremely diverse range of potential applications not only for biomonitoring of toxicants in aqueous environments, but also in biomedicine for identifying ROS-mediated mechanisms involved in the progression of a number of ... |
نوع الوثيقة: | article in journal/newspaper |
اللغة: | English |
تدمد: | 0160-4120 |
Relation: | Vol. 133, Part A, 105138; NE/L007371/1; http://hdl.handle.net/10871/39789; Environment International |
DOI: | 10.1016/j.envint.2019.105138 |
الاتاحة: | http://hdl.handle.net/10871/39789 https://doi.org/10.1016/j.envint.2019.105138 |
Rights: | © 2019 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/BY-NC-ND/4.0/). ; https://creativecommons.org/licenses/by-nc-nd/4.0/ |
رقم الانضمام: | edsbas.C1ED0186 |
قاعدة البيانات: | BASE |
تدمد: | 01604120 |
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DOI: | 10.1016/j.envint.2019.105138 |