Proteomic analysis of the olfactory mucosa, thoracic aorta, urinary bladder, and descending colon of smooth muscle alpha actin null mutant mice

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Wang, Yuxiang
colon , smooth muscle alpha actin , Proteomics , smooth muscle , aorta , bladder , OEC
Smooth muscle alpha actin is one of six mammalian isoforms and the predominant isoform in vascular smooth muscle. In mice and humans lacking functional SMAA, pathophysiological changes have been identified in the aorta, bladder, colon, and olfactory ensheathing cell population in the olfactory nervous system. These include impaired vascular contractility, thoracic aortic aneurysms and dissections, hypocontractile bladders, gastrointestinal hypoperistalsis, and pathological OEC development. Our investigation set out to compare the whole tissue proteomes of the olfactory epithelium, thoracic aorta, urinary bladder, and descending colon from age-matched adult SMAA null mice and their wild type siblings. This approach allowed us to better understand the mechanism of pathologies, the role of SMAA in these tissues, and to determine whether tissues compensate for a loss of this isoactin. Our objective was to systematically characterize changes in proteins that are of structural and/or contractile significance and in proteins that may be indirectly affected by lack of functional SMAA. We hypothesized that the expression of various cytoskeletal and contractile proteins will be altered in smooth muscle cell-rich tissues of mice lacking functional SMAA, thereby signifying adaptive and maladaptive changes. Through 2-dimensional gel electrophoresis and mass spectrometry, we found increased abundance of four proteins in the olfactory mucosa of SMAA null mice: alpha tubulin, precursors of vomeronasal secretory proteins I and II, and lipocalin 13 precursor. In the thoracic aorta of SMAA null mice, levels of skeletal muscle myosin essential and regulatory light chain, along with gamma actin, were increased, whereas levels of alpha cardiac muscle actin were decreased. In the urinary bladder, a loss of SMAA expression was accompanied by a decrease in skeletal muscle myosin essential and regulatory light chain levels. Lastly, in the descending colon we found reductions in annexin A5, chymotrypsinogen B precursor, ela 3 protein, and lithostathine 1 precursor. Together, these protein changes reveal remarkable adaptability of mammalian smooth muscle contractile protein expression and new relationships between SMAA and proteins that previously have not been associated with SMAA or smooth muscle contraction. This proteomic investigation has identified proteins that offer new directions for future investigations regarding SMAA function and SMAA-related pathologies.
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