Expression and function of Oat1 and Oat3 in rat kidney exposed to mercuric chloride.
This study was designed to evaluate the expression and function of the organic anion transporters, Oat1 and Oat3, in rats exposed to a nephrotoxic dose of HgCl(2). Oat1 protein expression increased in renal homogenates and decreased in renal basolateral membranes from HgCl(2) rats, while Oat3 protein abundance decreased in both kidney homogenates and basolateral membranes. The lower protein levels of Oat1 and Oat3 in basolateral membranes explain the lower uptake capacity for p-aminohippurate (in vitro assays) and the diminution of the systemic clearance of this organic anion (in vivo studies) observed in treated rats. Since both transporters mediate mercury access to the renal cells, their down-regulation in basolateral membranes might be a defensive mechanism developed by the cell to protect itself against mercury injury. The pharmacological modulation of the expression and/or the function of Oat1 and Oat3 might be an effective therapeutic strategy for reducing the nephrotoxicity of mercury.
Di Giusto
Gisela
G
Area Farmacología, Facultad de Ciencias Bioquímicas y Farmacéuticas, Universidad Nacional de Rosario, CONICET, Suipacha 531, Rosario, (2000), Argentina.
Anzai
Naohiko
N
Ruiz
María L
ML
Endou
Hitoshi
H
Torres
Adriana M
AM
D000818:Animals; D007668:Kidney / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008627:Mercuric Chloride / Q000378:metabolism / Q000493:pharmacokinetics / Q000633:toxicity*; D027362:Organic Anion Transport Protein 1 / Q000235:genetics / Q000378:metabolism*; D029362:Organic Anion Transporters, Sodium-Independent / Q000235:genetics / Q000378:metabolism*; D011084:Polycyclic Aromatic Hydrocarbons / Q000493:pharmacokinetics; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D018675:Toxicity Tests
D027362:Organic Anion Transport Protein 1; D029362:Organic Anion Transporters, Sodium-Independent; D011084:Polycyclic Aromatic Hydrocarbons; D012333:RNA, Messenger; C114338:organic anion transport protein 3; D008627:Mercuric Chloride