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Publication : High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications.

First Author  Aghdam SY Year  2013
Journal  Biochem Biophys Res Commun Volume  432
Issue  2 Pages  339-44
PubMed ID  23391566 Mgi Jnum  J:198848
Mgi Id  MGI:5499661 Doi  10.1016/j.bbrc.2013.01.101
Citation  Aghdam SY, et al. (2013) High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications. Biochem Biophys Res Commun 432(2):339-44
abstractText  The precise link between hyperglycemia and its deleterious effects on retinal and kidney microvasculature, and more specifically loss of retinal perivascular supporting cells including smooth muscle cell/pericytes (SMC/PC), in diabetes are not completely understood. We hypothesized that differential cellular proteasome activity contributes to sensitivity of PC to high glucose-mediated oxidative stress and vascular rarefaction. Here we show that retinal endothelial cells (EC) have significantly higher proteasome peptidase activity compared to PC. High glucose treatment (HGT) increased the level of total ubiquitin-conjugated proteins in cultured retinal PC and EC, but not photoreceptor cells. In addition, in vitro proteasome activity assays showed significant impairment of proteasome chymotrypsin-like peptidase activity in PC, but not EC. The PA28-alpha/-beta and PA28-beta/-gamma protein levels were also higher in the retina and kidney glomeruli of diabetic mice, respectively. Our results demonstrate, for the first time, that high glucose has direct biological effects on cellular proteasome function, and this modulation might be protective against cellular stress or damage induced by high glucose.
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