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Neurotoxicity of environmental pollutants

Al-Mousa, Fawaz Ali F (2011)
Ph.D. thesis, University of Birmingham.

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Abstract

Brominated flame retardants (BFRs) and alkylphenols (APs) are pollutants commonly found within the environment and have human health concerns due to their endocrine disrupting and cytotoxic effects. BFRs are used to reduce the flammability of a variety of consumer products such as foam furnishings, whereas APs are found in plastic products used by the food industry. This study investigated the neurotoxicity of the most commonly used groups of BFRs and APs on SH-SY5Y human neuroblastoma cells. The results presented in this thesis showed (using cell viability assays) that these pollutants are toxic at low concentrations. Some compounds such as hexabromocyclododecane (HBCD) and 4-nonylphenol (4-NP) induce cell death (apoptosis) by caspases activation (Casp-8, Casp-9 and Casp-3) and cytochrome c release at low micromolar concentrations (IC50 ~ 4μM and 6μM, respectively). Consequently this study also showed that these compounds increased intracellular [Ca2+] levels and the production of reactive oxygen species (ROS) within SH-SY5Y cells by causing Ca2+-dependent depolarization of the mitochondria. In support of a Ca2+-mediated mechanism, the data presented here shows that some BFRs and APs inhibit Sarcoplasmic/ Endoplasmic Ca2+-ATPase (SERCA) and to corroborate this over-expressing SERCA1 improved cell viability especially in cells exposed to certain cytotoxic chemicals such as HBCD; this study is the first experiment of this type to be performed. This study also showed that some of these chemicals, at low concentrations had amyloidgenic effects causing the cleavage amyloid precursor protein (APP) into Beta-amyloid (Aβ) and could therefore be implicated in Alzheimer‟s disease (AD).

Type of Work:Ph.D. thesis.
Supervisor(s):Michelangeli, Frank and Waring, Rosemary
School/Faculty:Colleges (2008 onwards) > College of Life & Environmental Sciences
Department:School of Biosciences
Subjects:QR Microbiology
Institution:University of Birmingham
ID Code:1461
This unpublished thesis/dissertation is copyright of the author and/or third parties. The intellectual property rights of the author or third parties in respect of this work are as defined by The Copyright Designs and Patents Act 1988 or as modified by any successor legislation. Any use made of information contained in this thesis/dissertation must be in accordance with that legislation and must be properly acknowledged. Further distribution or reproduction in any format is prohibited without the permission of the copyright holder.
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