title: Selective protection of renal tubular epithelial cells by heme oxygenase (HO)-1 during stress-induced injury.
abstract: BACKGROUND
  The renal pathology of human heme oxygenase (HO)-1 deficiency is characterized by advanced tubulointerstitial injury, whereas the glomerular structures are affected little. These facts suggest that the renal tubuli are dependent on intrinsic HO-1 production for their survival under oxidative stresses.
  
  
  METHODS
  We compared the patterns of HO-1 expression by primary cultured human mesangial cells (HMCs) and renal proximal tubular epithelial cells (HRPTECs) in vitro. Furthermore, the cytoprotective roles of HO-1 induced in these cells were evaluated by stress-induced cytotoxicity assays. HO-1 expressions in HRPTECs and HMCs were evaluated by immunoblotting, and by reverse transcriptase (RT) and/or real time polymerase chain reaction (PCR).
  
  
  RESULTS
  In HRPTECs, both HO-1 mRNA expression and protein production peaked at around 12 h and persisted until 24 h after hemin stimulation. In contrast, HO-1 mRNA expression and protein production by HMCs peaked at 4 h and 6 h respectively, and the levels declined rapidly, being undetectable at 24 h. The peak level of HO-1 expression was significantly higher in HRPTECs than in HMCs. Oxidative stress-induced cell injury in HRPTECs was significantly reduced when HO-1 production had been induced prior to the culture. In contrast, HO-1 induction had little cytoprotective effect on HMCs. Tin protoporphyrin (SnPP), an inhibitor of HO function, significantly reversed the cytoprotection by HO-1.
  
  
  CONCLUSIONS
  These data suggest that HRPTECs are more susceptible to oxidative stress and are significantly more dependent on HO-1 for protection against noxious stimuli than HMCs. Collectively, these results indicate that HO-1 is an important protective factor for kidney tissue, in particular, renal tubular epithelial cells.
authors.affiliation: Department of Pediatrics, Graduate School of Medical Science, Kanazawa University, Ishikawa, Japan.
authors.forename: Yonghong
authors.initials: Y
authors.lastname: Yang
authors.forename: Kazuhide
authors.initials: K
authors.lastname: Ohta
authors.forename: Masaki
authors.initials: M
authors.lastname: Shimizu
authors.forename: Kayoko
authors.initials: K
authors.lastname: Morimoto
authors.forename: Chinami
authors.initials: C
authors.lastname: Goto
authors.forename: Akiko
authors.initials: A
authors.lastname: Nakai
authors.forename: Tomoko
authors.initials: T
authors.lastname: Toma
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Kasahara
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yachie
authors.forename: Hidetoshi
authors.initials: H
authors.lastname: Seki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Koizumi
mesh_terms: D002478:Cells, Cultured; D019610:Cytoprotection / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004847:Epithelial Cells / Q000201:enzymology / Q000473:pathology; D005920:Glomerular Mesangium / Q000201:enzymology / Q000473:pathology; D006419:Heme Oxygenase (Decyclizing) / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D051547:Heme Oxygenase-1; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D007687:Kidney Tubules, Proximal / Q000201:enzymology* / Q000473:pathology*; D008565:Membrane Proteins; D008665:Metalloporphyrins / Q000494:pharmacology; D018384:Oxidative Stress; D011524:Protoporphyrins / Q000494:pharmacology; D012333:RNA, Messenger / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D008565:Membrane Proteins; D008665:Metalloporphyrins; D011524:Protoporphyrins; D012333:RNA, Messenger; D006427:Hemin; C032628:tin protoporphyrin IX; C496541:HMOX1 protein, human; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1