title: [Effect of rapamycin on high glucose-induced autophagy impairment, oxidative stress and premature senescence in rat mesangial cells in vitro].
abstract: OBJECTIVE
  To investigate the effects of rapamycin and 3-methyladenine on autophagy impairment, oxidative stress and premature senescence induced by high-glucose in primarily cultured rat mesangial cells.
  
  
  METHODS
  Rat glomerular mesangial cells (GMCs) were isolated and cultured in normal glucose, high glucose, high glucose with 3-methyladenine (3-MA), or high glucose with rapamycin. At 24 h, 72 h and 10 days of culture, the cells were examined for expression levels of autophagy markers LC3 and p62/SQSTM1, malondialdehyde (MDA) and protein carbonyl, β-galactosidase (SA-β-gal) activity and heterochromatin foci (SAHF).
  
  
  RESULTS
  Compared with those of normal cell culture, the cells exposed to high glucose for 72 h and 10 days showed down-regulated LC3 expression, up-regulated p62/SQSTM1 expression, elevated MDA and protein carbonyl levels, and increased SAHF formation and percentage of SA-β-gal-positive cells. These changes were reversed in GMCs exposed to high glucose and rapamycin for 72 h and 10 days, but exacerbated in cells incubated with 3-MA.
  
  
  CONCLUSIONS
  High glucose can suppress autophagic function of rat GMCs to result in oxidative damage and cell senescence. Rapamycin can attenuate autophagy impairment, oxidative damage and senescence induced by high glucose, whereas 3-MA can further aggravate high glucose-induced cell injuries in rat GMCs.
authors.affiliation: Department of Nephrology, State Key Laboratory of Kidney Diseases, General Hospital of PLA, Beijing 100853, China. lijin1001@126.com
authors.forename: Jin
authors.initials: J
authors.lastname: Li
authors.forename: Xueyuan
authors.initials: X
authors.lastname: Bai
authors.forename: Shaoyuan
authors.initials: S
authors.lastname: Cui
authors.forename: Bo
authors.initials: B
authors.lastname: Fu
authors.forename: Xiangmei
authors.initials: X
authors.lastname: Chen
mesh_terms: D000818:Animals; D001343:Autophagy / Q000187:drug effects*; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects*; D005920:Glomerular Mesangium / Q000166:cytology; D005947:Glucose / Q000009:adverse effects; D008297:Male; D050527:Mesangial Cells / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology*
chemical_list: D005947:Glucose; D020123:Sirolimus