Preconditioning with cyclosporine A or FK506 differentially regulates mitogen-activated protein kinase expression in rat kidneys with ischemia/reperfusion injury.
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.
Yang
Chul Woo
CW
Department of Internal Medicine, The Catholic University of Korea, Seoul, Korea.
Ahn
Hee Jong
HJ
Jung
Ju Young
JY
Kim
Wan Young
WY
Li
Can
C
Choi
Bum Soon
BS
Kim
Hyung Wook
HW
Kim
Yong Soo
YS
Moon
In Sung
IS
Kim
Jin
J
Bang
Byung Kee
BK
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
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; D016559:Tacrolimus