title: Effect of angiotensin II type 1 receptor blocker on 12-lipoxygenase activity and slit diaphragm protein expression in type 2 diabetic rat glomeruli.
abstract: BACKGROUND
  The 12-lipoxygenase (12-LO) and angiotensin II (Ang II) interaction plays an important role in diabetic nephropathy (DN). Proteinuria in DN is associated with decreased slit diaphragm proteins including nephrin and P-cadherin. Therefore, we investigated whether Ang II type 1 receptor (AT1) blocker (ARB) regulates 12-LO activity and slit diaphragm protein expression in diabetic rat glomeruli.
  
  
  METHODS
  Glomeruli were isolated with the sieving method, and classified into small glomeruli (SG; 75-μm sieve) and large glomeruli (LG; 125-μm sieve).
  
  
  RESULTS
  12(S)-HETE, a lipid product of 12-LO, was increased by Ang II in the glomeruli. Infusion of 12(S)-HETE and Ang II significantly decreased nephrin expression in LG, but increased it in SG compared to control. Glomerular P-cadherin expression was reduced after Ang II and 12(S)-HETE treatment without differences between LG and SG. ARB did not influence glycemic levels but completely abolished the increases in 12(S)-HETE, AT1 expression, and proteinuria in diabetic rats. Nephrin expression was significantly reduced in LG but increased in SG in diabetic rats compared to control. P-cadherin expression decreased in both diabetic LG and SG. The abnormalities of nephrin and P-cadherin were partially but significantly reversed by ARB.
  
  
  CONCLUSIONS
  ARB potentially ameliorates DN via the up-regulation of glomerular nephrin and P-cadherin expression through the inhibition of 12-LO activation in the glomeruli of rats with DN.
authors.affiliation: Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China.
authors.forename: Hong-Zhao
authors.initials: HZ
authors.lastname: Xu
authors.affiliation: Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China.
authors.forename: Wan-Ning
authors.initials: WN
authors.lastname: Wang
authors.affiliation: Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Zhang
authors.affiliation: Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China.
authors.forename: Yan-Li
authors.initials: YL
authors.lastname: Cheng
authors.affiliation: Department of Nephrology, The First Hospital of Jilin University, 71 Xinmin Street, Changchun, 130021, Jilin, China. renalxu@163.com.
authors.forename: Zhong-Gao
authors.initials: ZG
authors.lastname: Xu
mesh_terms: D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D001092:Arachidonate 12-Lipoxygenase / Q000378:metabolism*; D015820:Cadherins / Q000378:metabolism*; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003924:Diabetes Mellitus, Type 2 / Q000139:chemically induced / Q000188:drug therapy* / Q000201:enzymology; D003928:Diabetic Nephropathies / Q000201:enzymology / Q000209:etiology / Q000517:prevention & control*; D059305:Diet, High-Fat; D007678:Kidney Glomerulus / Q000187:drug effects* / Q000201:enzymology; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology*; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D050199:Podocytes / Q000187:drug effects / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000187:drug effects* / Q000378:metabolism; D012084:Renin-Angiotensin System / Q000187:drug effects; D013311:Streptozocin
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015820:Cadherins; D016859:Lipoxygenase Inhibitors; D008565:Membrane Proteins; D044140:Receptor, Angiotensin, Type 1; C113267:nephrin; D000804:Angiotensin II; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D013311:Streptozocin; D001092:Arachidonate 12-Lipoxygenase; D019808:Losartan
keywords: 12(S)-HETE; Angiotensin II; Diabetic nephropathy; Nephrin; P-cadherin