[Truncated abstract] UCP2 (Uncoupling protein 2) belongs to the family of mitochondrial carrier proteins. It is expressed in the inner mitochondrial membrane (IMM) and is a known regulator of mitochondrial function. UCP2 is best characterized as a regulator of reactive oxygen species (ROS) during electron transport in the IMM. Macrophages exist in various tissue environments and represent many cell types including tissue macrophages, inflammatory macrophages, dendritic cells and osteoclasts (Gordon et al., 2005). These various cell types have specialisation that reflects the tissue environment that they populate or are recruited to. Recruitment of macrophages to inflammatory tissue sites for example is associated with the production of intracellular ROS as an important host defense mechanism against pathogenic organisms that can find sanctuary intracellulary (Arsenijevic et al., 2000). Production of ROS may have more defined roles in cell signaling, regulation and recruitment (Jackson, 2002). There is limited information of how ROS and in particular the type of ROS species affect the various points of UCP2 regulation (including protein synthesis, gene transcription, mRNA abundance and protein degradation rate) in macrophages. Understanding the points of regulation of UCP2 in macrophages is important clinically in disease states including atherosclerosis and ischemic insult/ re-perfusion injury where ROS elevation plays a role in progression of these disease states. The presence of UCP2 mRNA, but not protein, in many non-macrophage tissues then suggests that similar regulation may be available beyond macrophage-lineage cells, allowing UCP2 protein expression, under conditions of mitochondrial oxidative stress, and perhaps other environmental stresses.
|Qualification||Doctor of Philosophy|
|Publication status||Unpublished - 2011|