title: Externalization of phosphatidylserine via multidrug resistance 1 (MDR1)/P-glycoprotein in oxalate-treated renal epithelial cells: implications for calcium oxalate urolithiasis.
abstract: OBJECTIVE
  We investigated the possible involvement of multidrug resistance protein 1 P-glycoprotein (MDR1 P-gp) in the oxalate-induced redistribution of phosphatidylserine in renal epithelial cell membranes.
  
  
  METHODS
  Real-time PCR and western blotting were used to examine MDR1 expression in Madin-Darby canine kidney cells at the mRNA and protein levels, respectively, whereas surface-expressed phosphatidylserine was detected by the annexin V-binding assay.
  
  
  RESULTS
  Oxalate treatment resulted in increased synthesis of MDR1, which resulted in phosphatidylserine (PS) externalization in the renal epithelial cell membrane. Treatment with the MDR1 inhibitor PSC833 significantly attenuated phosphatidylserine externalization. Transfection of the human MDR1 gene into renal epithelial cells significantly increased PS externalization.
  
  
  CONCLUSIONS
  To our knowledge, this study is the first to show that oxalate increases the synthesis of MDR1 P-gp, which plays a key role in hyperoxaluria-promoted calcium oxalate urolithiasis by facilitating phosphatidylserine redistribution in renal epithelial cells.
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yu-Hang
authors.initials: YH
authors.lastname: Li
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Shi-Liang
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xiu-Guo
authors.initials: XG
authors.lastname: Gan
authors.affiliation: Department of Central Laboratory, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Shang-Ha
authors.initials: SH
authors.lastname: Pan
authors.affiliation: Department of Central Laboratory of Blood Cancer, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Yue-Qiu
authors.initials: YQ
authors.lastname: Teng
authors.affiliation: Department of Urology Surgery, First Affiliated Hospital of Harbin Medical University, Harbin, People's Republic of China. RuiHuaAn@126.com.
authors.forename: Rui-Hua
authors.initials: RH
authors.lastname: An
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism / Q000473:pathology; D002478:Cells, Cultured; D003524:Cyclosporins / Q000494:pharmacology; D004285:Dogs; D018432:Drug Resistance, Multiple; D005434:Flow Cytometry; D005786:Gene Expression Regulation; D006801:Humans; D053040:Nephrolithiasis / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism; D010070:Oxalates / Q000009:adverse effects*; D010718:Phosphatidylserines / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019459:Urothelium / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D003524:Cyclosporins; D010070:Oxalates; D010718:Phosphatidylserines; D012333:RNA, Messenger; C070272:valspodar
keywords: Calcium oxalate; Epithelium; MDR1 P-glycoprotein; Nephrolithiasis; Phosphatidylserine