Edginton, M.A.; (2005) An investigation into the expression and function of uncoupling protein 2 during neonatal sepsis. Masters thesis , University of London.

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Abstract

Uncoupling protein 2 (UCP2) is widely expressed in mammals but its true function has not been established. Present information suggests that like UCP1, UCP2 functions as a proton leak and can uncouple productive mitochondrial respiration. This activity is reported to be functionally dependant on the presence of ubiquinone. The expression of UCP2 is reportedly increased during endotoxaemia, thus it may have a role in immune response. This study examines the expression of UCP2 protein and its possible function during infection using endotoxamia in suckling rat pups as a model for neonatal sepsis. The whole body response to endotoxaemia was investigated using indirect calorimetry. We report that endotoxamia induces hypometabolism and hypothermia in neonatal rats. The expression pattern of UCP2 was investigated by developing a protocol for UCP2 western blotting and then using this to analyse appropriate mitochondrial samples from control and endotoxic suckling rats. UCP2 expression was strongest in mitochondrial preparations from spleen and lung tissue. It was demonstrated that when compared to control samples, UCP2 expression is increased and ubiquinone levels are decreased in mitochondrial preparations from lung tissues of endotoxic rat pups. The increase of UCP2 in endotoxic lung mitochondria could be the result of macrophage infiltration and the decrease in ubiquinone may reflect recruitment of this compound to the plasma membrane. It is possible that the function of uncoupling may be to protect sensitive tissues from damage by free radicals. The role of UCP2 induced uncoupling in macrophages was investigated by reactive oxygen species (ROS) assays. Using in vitro assays of macrophage ROS generation we demonstrate that known activators of UCP2 such as TTNBP and ubiquinone enriched media can reduce the level of ROS Our findings support other studies that suggest that UCP2 may be involved in protecting against the detrimental effects of ROS.

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