title: Impact of high glucose and proteasome inhibitor MG132 on histone H2A and H2B ubiquitination in rat glomerular mesangial cells.
abstract: BACKGROUND
  Hyperglycemia plays a pivotal role in the development of diabetic nephropathy (DN) and may be related to epigenetic metabolic memory. One of the most crucial epigenetic mechanisms is histone modification, which is associated with the expression of a fibrosis factor in vascular injury. Aim .In this study, we investigated the ubiquitination of histones H2A and H2B to explore the epigenetic mechanisms of DN.
  
  
  METHODS
  The GMCs were cultured as follows: normal group, high glucose group, mannitol group, and intervention group. After 12 hr, 24 hr, and 48 hr, histones ubiquitination, transforming growth factor-β (TGF-β), and fibronectin (FN) were measured using WB, RT-PCR, and IF.
  
  
  RESULTS
  High glucose can induce the upregulation of FN. H2A ubiquitination in GMCs increased in high glucose group (P < 0.01), whereas it decreased significantly in intervention group (P < 0.05). In contrast, H2B ubiquitination decreased with an increasing concentration of glucose, but it was recovered in the intervention group (P < 0.05). Expression of TGF-β changed in response to abnormal histone ubiquitination.
  
  
  CONCLUSIONS
  The high glucose may induce H2A ubiquitination and reduce H2B ubiquitination in GMCs. The changes of histone ubiquitination may be due in part to DN by activating TGF-β signaling pathway.
authors.affiliation: Department of Endocrinology, Affiliated Hospital of Luzhou Medical College, Luzhou 646000, China.
authors.forename: Chenlin
authors.initials: C
authors.lastname: Gao
authors.forename: Guo
authors.initials: G
authors.lastname: Chen
authors.forename: Li
authors.initials: L
authors.lastname: Liu
authors.forename: Xia
authors.initials: X
authors.lastname: Li
authors.forename: Jianhua
authors.initials: J
authors.lastname: He
authors.forename: Lan
authors.initials: L
authors.lastname: Jiang
authors.forename: Jianhua
authors.initials: J
authors.lastname: Zhu
authors.forename: Yong
authors.initials: Y
authors.lastname: Xu
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005353:Fibronectins / Q000235:genetics / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology*; D006657:Histones / Q000235:genetics / Q000378:metabolism*; D006943:Hyperglycemia / Q000235:genetics / Q000378:metabolism; D007976:Leupeptins / Q000494:pharmacology*; D050527:Mesangial Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D015853:Cysteine Proteinase Inhibitors; D005353:Fibronectins; D006657:Histones; D007976:Leupeptins; D016212:Transforming Growth Factor beta; D005947:Glucose; C072553:benzyloxycarbonylleucyl-leucyl-leucine aldehyde