Upregulation of rat renal cortical organic anion transporter (OAT1 and OAT3) expression in response to ischemia/reperfusion injury.
OBJECTIVE
Renal organic anion transporters (OAT1 and OAT3) localized in the basolateral membrane mediate the uptake of organic anions from the blood into proximal tubules. This study aimed to examine the effects of renal ischemia/reperfusion injury (IRI) on the expression of cortical renal OAT1 and OAT3 and the functional impact.


METHODS
Male rats underwent a right nephrectomy and clamping of the left renal pedicle for 50 min or sham operation, followed by reperfusion for 1, 2, 4 and 6 days. The expression of OAT1 and OAT3 was detected by RT-PCR, immunohistochemistry and Western blot analysis. Na(+)-K(+)-ATPase activity was also estimated.


RESULTS
The renal clearance of para-aminohippurate was significantly decreased on day 1 in IRI rats compared with sham-operated rats and returned to normal when the tubular injury recovered. There were significant increases in the mRNA and protein levels of OAT1 and OAT3 in renal cortex homogenates and basolateral membranes on day 1 after IRI, while on days 2 and 4 after IRI, the renal expression of OAT1 and OAT3 decreased gradually but was still significantly higher than that of the sham-operated rats. The Na(+)-K(+)-ATPase activity in renal cortex homogenates decreased significantly on day 1 after IRI but gradually increased on days 2, 4 and 6.


CONCLUSIONS
Renal para-aminohippurate clearance was depressed in response to IRI; however, the expressions of renal cortex OAT1 and OAT3 were significantly elevated in the early stage of IRI which may have substantial impact on renal excretion of some drugs and toxic compounds.
Zhang
Rui
R
Department of Nephrology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Yang
Xiao
X
Li
Jun
J
Wu
Jun
J
Peng
Wen-Xing
WX
Dong
Xiu-Qing
XQ
Zhou
Shu-Feng
SF
Yu
Xue-Qing
XQ
D000818:Animals; D015153:Blotting, Western; D007150:Immunohistochemistry; D007672:Kidney Cortex / Q000737:chemistry*; D008297:Male; D027362:Organic Anion Transport Protein 1 / Q000032:analysis*; D029362:Organic Anion Transporters, Sodium-Independent / Q000032:analysis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation; D010130:p-Aminohippuric Acid / Q000378:metabolism
D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; C114338:organic anion transport protein 3; D010130:p-Aminohippuric Acid