Preconditioning with 1,25-dihydroxyvitamin D3 protects against subsequent ischemia-reperfusion injury in the rat kidney.
OBJECTIVE
Induction of heat shock protein 70 (HSP70) is important in the tolerance of subsequent ischemia-reperfusion (I/R) injury. The aim of this study was to evaluate the effect of HSP70 induction by 1,25-dihydroxyvitamin D3 (VD3) on subsequent I/R injury in rats.


METHODS
HSP70 was induced in Sprague-Dawley rats by VD3 treatment for 7 days, and the effect of VD3 pretreatment on subsequent I/R injury was evaluated in terms of renal function, tubular necrosis score, tumor necrosis factor alpha mRNA expression, mitogen-activated protein kinase expression, and proliferating cell nuclear antigen expression.


RESULTS
VD3 treatment increased HSP70 expression which was localized to renal tubular cells in the outer medulla. Pretreatment with VD3 before I/R injury resulted in (1) decreased blood urea nitrogen and serum creatinine levels; (2) decreased tubular cell necrosis; (3) increased tubular cell proliferation as determined by proliferating cell nuclear antigen expression; (4) decreased tumor necrosis factor alpha mRNA expression, and (5) increased extracellular signal regulated protein kinase and decreased c-Jun N-terminal kinase expression.


CONCLUSIONS
Our study demonstrates that VD3 is a nontoxic inducer of HSP70 and exerts a protective effect against subsequent I/R injury.
Kim
Young Ok
YO
Department of Internal Medicine, The Catholic University of Korea College of Medicine, Seoul, Korea.
Li
Can
C
Sun
Bo Kyung
BK
Kim
Jung Sim
JS
Lim
Sun Woo
SW
Choi
Bun Soon
BS
Kim
Yong Soo
YS
Kim
Jin
J
Bang
Byung Kee
BK
Yang
Chul Woo
CW
D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis* / Q000502:physiology; D007150:Immunohistochemistry; D007668:Kidney / Q000098:blood supply* / Q000473:pathology / Q000502:physiology; D008297:Male; D018809:Proliferating Cell Nuclear Antigen / Q000032:analysis; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000517:prevention & control*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D002120:Calcium Channel Agonists; D018840:HSP70 Heat-Shock Proteins; D018809:Proliferating Cell Nuclear Antigen; D012333:RNA, Messenger; D002117:Calcitriol