The role of Na+/Ca2+ exchanger in endothelin-1-aggravated hypoxia/reoxygenation-induced injury in renal epithelial cells.
We analyzed the role of the Na+/Ca2+ exchanger (NCX) in endothelin-1-aggravated hypoxia/reoxygenation-induced injury in renal epithelial LLC-PK1 cells. KB-R7943, a selective NCX inhibitor, suppressed hypoxia/reoxygenation-induced cell damage, whereas overexpression of NCX1 into cells enhanced it. Endothelin-1 significantly aggravated hypoxia/reoxygenation-induced injury in parental and NCX1-overexpressing LLC-PK1 cells. Such aggravation by endothelin-1 was not observed in cells overexpressing a deregulated NCX1 mutant, which displays no protein kinase C-dependent activation. These results suggest that Ca2+ overload via NCX plays a critical role in hypoxia/reoxygenation-induced renal tubular injury, and that endothelin-1 aggravates the cell damage through the activation of NCX.
Kita
Satomi
S
Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 814-0180, Japan.
Furuta
Ayako
A
Takano
Yukio
Y
Iwamoto
Takahiro
T
D000818:Animals; D019332:Endothelin-1 / Q000502:physiology*; D004847:Epithelial Cells / Q000473:pathology; D000860:Hypoxia / Q000503:physiopathology*; D007668:Kidney / Q000473:pathology*; D018374:LLC-PK1 Cells; D010100:Oxygen / Q000378:metabolism*; D013552:Swine; D013890:Thiourea / Q000031:analogs & derivatives / Q000494:pharmacology
C101670:2-(2-(4-(4-nitrobenzyloxy)phenyl)ethyl)isothiourea methanesulfonate; D019332:Endothelin-1; D013890:Thiourea; D010100:Oxygen