Glycemic control declines with advancing age as reflected by the high percentage of the population aged 65 years and older who are glucose intolerant. Elevated plasma glucose levels have been demonstrated to prematurely lead to many age-associated pathologies, including cardiovascular disease (CVD). Studies elucidating the molecular mechanisms of glucose stress have largely focused on that of high-glucose stress and shown an altered cellular physiology that contributes to diminished reserve capacity. One of the major hurdles in the treatment of elevated plasma glucose levels is the high incidence of hypoglycemic episodes. Similar to elevated glucose, the clinical manifestations of low blood glucose also lead to premature age-associated pathologies, although the molecular mechanisms have been less well characterized. Here we report on the role of a Serum Response Factor (SRF)-binding protein, p49/STRAP (SRFBP1a), in the context of in cellular aging and in response to low-glucose stress in vitro. We demonstrate that p49/STRAP is increased with advancing age in vitro. We also observed that p49/STRAP is increased in response to low-glucose. Elevated p49/STRAP reduced mitochondrial function. p49/STRAP overexpression correlated with reduced cell size, and an increased level of cofilins, proteins involved in f-actin cytoskeletal degradation. Reduced mitochondrial function and altered cytoskeletal rearrangements are observed in a number of age-associated phenotypes, including cellular replicative senescence. Our findings suggest that p49/STRAP is invovled cellular response to low-glucose stress. p49/STRAP likely also mediates, in part, the cytoskeletal changes during replicative and/or functional senescence.
|Advisor:||Wei, Jeanne Y.|
|Commitee:||Benes, Helen, Ponnappan, Usha, Wolf, Robert, Zhang, Xiaomin|
|School:||University of Arkansas for Medical Sciences|
|Department:||Interdisciplinary Biomedical Sciences|
|School Location:||United States -- Arkansas|
|Source:||DAI-B 77/11(E), Dissertation Abstracts International|
|Subjects:||Cellular biology, Aging|
|Keywords:||F-actin, Glucose, SRF, Vimentin, p49/STRAP|
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