title: High glucose and diabetes modulate cellular proteasome function: Implications in the pathogenesis of diabetes complications.
abstract: 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-α/-β and PA28-β/-γ 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.
authors: Department of Ophthalmology & Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, WI 53792-4673, USA.
authors: Saeed Yadranji
authors: SY
authors: Aghdam
authors: Zafer
authors: Z
authors: Gurel
authors: Alireza
authors: A
authors: Ghaffarieh
authors: Christine M
authors: CM
authors: Sorenson
authors: Nader
authors: N
authors: Sheibani
mesh_terms: D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D002829:Choroid / Q000201:enzymology; D044842:Cullin Proteins / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000201:enzymology*; D003930:Diabetic Retinopathy / Q000201:enzymology*; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000201:enzymology*; D007678:Kidney Glomerulus / Q000201:enzymology; D051379:Mice; D009124:Muscle Proteins / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D012160:Retina / Q000187:drug effects / Q000201:enzymology*; D054875:Ubiquitination
chemical_list: D001786:Blood Glucose; C503645:CUL3 protein, human; C100318:Cullin 1; D044842:Cullin Proteins; D009124:Muscle Proteins; C085047:PSME1 protein, human; C486207:PSME2 protein, human; D046988:Proteasome Endopeptidase Complex; D005947:Glucose
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