title: Preconditioning with cyclosporine A or FK506 differentially regulates mitogen-activated protein kinase expression in rat kidneys with ischemia/reperfusion injury.
abstract: BACKGROUND
  The signaling pathways of mitogen-activated protein kinases (MAPKs) are important molecular components responsible for ischemia/reperfusion (I/R) injury in the kidneys. Preconditioning with cyclosporine A (CsA) or FK506 reduces subsequent I/R injury. We studied the effect of preconditioning with CsA or FK506 on MAPK expression in ischemic rat kidneys.
  
  
  METHODS
  Two separate studies were performed using Sprague-Dawley rats. First, MAPK (extracellular signal-regulated kinase [ERK], jun N-terminal kinase [JNK], p38) expressions were observed at 0, 10, 20, 30, 60, 120, and 1,440 min after I/R injury. Second, the effects of preconditioning with CsA or FK506 on MAPK expressions were observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min. Rats were pretreated with intravenous (IV) CsA (3 mg/kg) or IV FK506 (0.3 mg/kg) 6 hr before I/R injury and killed 30 min later. Expression of MAPK was measured using immunoblot and immunohistochemistry.
  
  
  RESULTS
  MAPK (ERK, JNK, p38) expressions were significantly increased in kidneys with I/R injury compared with sham-operated controls, and immunohistochemistry revealed increased MAPK immunoreactivity in renal tubules of the outer medulla. Kidneys preconditioned with low-dose CsA or FK506 showed significantly increased ERK expression compared with kidneys with I/R injury alone (CsA, 9.5- vs. 4.5-fold; FK506 10.4- vs. 4.5-fold: P<0.05) but showed decreased JNK (CsA, 3.8- vs. 5.3-fold; FK506, 3.4- vs. 5.3-fold: P<0.05) and p38 expression (CsA, 2.5- vs. 3.7-fold; FK506, 2.1- vs. 3.7-fold: P<0.05).
  
  
  CONCLUSIONS
  Preconditioning with CsA or FK506 differentially regulates the expression of MAPK in rat kidneys with I/R injury, and this may explain the remarkable protective effects of these agents.
authors.affiliation: Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
authors.forename: Chul Woo
authors.initials: CW
authors.lastname: Yang
authors.forename: Hee Jong
authors.initials: HJ
authors.lastname: Ahn
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Jung
authors.forename: Wan Young
authors.initials: WY
authors.lastname: Kim
authors.forename: Can
authors.initials: C
authors.lastname: Li
authors.forename: Bum Soon
authors.initials: BS
authors.lastname: Choi
authors.forename: Hyung Wook
authors.initials: HW
authors.lastname: Kim
authors.forename: Yong Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: In Sung
authors.initials: IS
authors.lastname: Moon
authors.forename: Jin
authors.initials: J
authors.lastname: Kim
authors.forename: Byung Kee
authors.initials: BK
authors.lastname: Bang
mesh_terms: D000818:Animals; D016572:Cyclosporine / Q000494:pharmacology*; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D007511:Ischemia / Q000201:enzymology*; D019194:Ischemic Preconditioning; D048031:JNK Mitogen-Activated Protein Kinases; D007668:Kidney / Q000098:blood supply* / Q000201:enzymology*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000201:enzymology*; D016559:Tacrolimus / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D016559:Tacrolimus