Genomic and Proteomic Analyses of the Methionine Sulfoxide Reductase A Knockout Mouse

Derek   B.   Oien; Xinkun      Wang; Jackob      Moskovitz

Abstract

In this review we describe the effects of methionine sulfoxide reductase A (MsrA) ablation in mouse tissues on the expression of various mRNAs and proteins, with an emphasis on brain tissues. Initially, the expression / activity levels of preselected proteins relevant to the methionine sulfoxide reductase system in various tissues are discussed (the list of proteins contains: thioredoxin, thioredoxin reductase, methionine sulfoxide reductase B, glucose-6-phosphate dehydrogenase, gluthathione peroxidase, selenoprotein P, and cysteine dioxygenase). Additionally, the consequences from lack of MsrA on protein oxidation (carbonylation and methionine oxidation) are evaluated. Finally, newly generated unpublished data is presented on genomic and proteomic analyses, compared between MsrA-/- and wild-type control brains. The gathered information is sorted out into three major protein groups that are linked to: 1) oxidative stress / apoptosis / degradation; 2) neuroregulation; and 3) signal transduction / transcription / elongation factors. In summary, the importance and relevance of MsrA in protecting against the development and progression of neurodegenerative diseases is reviewed.

Keywords: Methionine oxidation, methionine sulfoxide reductase, oxidative stress, selenoprotein, antioxidant

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