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Title: Targeted sensors to monitor oxidative stress in the endoplasmic reticulum
Author: Martin, Rachel E.
ISNI:       0000 0004 5349 2096
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 2014
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Hydrogen peroxide has a diverse array of functions in cells. Not only as a mediator of oxidative stress, it is also involved in signalling in many pathways including tyrosine phosphorylation, sumoylation, proliferation and differentiation and cysteine oxidation [1]. There are a number of different producers of hydrogen peroxide in the cell including the NADPH oxidase (Nox) family of enzymes [2], the electron transport chain in the mitochondria [3] and disulfide bond formation in the endoplasmic reticulum (ER) [4]. In order to prevent a toxic build-up of hydrogen peroxide the cell also deploys a range of antioxidant enzymes including catalase, the glutathione peroxidases (GPxs) and the peroxiredoxins (Prxs) [5]. Therefore at all times a balance must be maintained to allow enough hydrogen peroxide production to allow for signalling to occur but at the same time ensuring the concentration does not increase enough to cause any oxidative damage. Oxidative damage is associated with aging in general and diseases including cancer, cardiovascular disorders and neurodegenerative diseases. For such diseases to occur the balance of hydrogen peroxide production and removal must be tipped and it is the elucidation of these processes with regards to the ER that we hope to achieve. We present the development and use of a novel sensor, BGB, which specifically detects hydrogen peroxide in the ER. BGB works in conjunction with the SNAPtag system to allow specific targeting of a small molecule probe to the ER. BGB is selective for hydrogen peroxide over other reactive oxygen species due to the use of a boronic acid group as the reactive moiety. We have developed MALDITOF mass spectrometry methods for quantitative analysis of this probe when used both and . Also included is the development of Pep-B, a probe which was designed to measure hydrogen peroxide in the ER, but using a peptide targeting system rather than SNAP-tag, an investigation into the synthesis of a fluorophore based probe and the development of an alternative method of analysis of BGB using an antibody based system which negates the requirement of MALDI-TOF.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available
Keywords: QH301 Biology