Renal organic anion transporter 1 is maldistributed and diminishes in proximal tubule cells but increases in vasculature after ischemia and reperfusion

Am J Physiol Renal Physiol. 2008 Dec;295(6):F1807-16. doi: 10.1152/ajprenal.90409.2008. Epub 2008 Oct 15.


Renal solute clearances are reduced in ischemic acute kidney injury. However, the mechanisms explaining how solute clearance is impaired have not been clarified. Recently, we reported that cadaveric renal allografts exhibit maldistribution of organic anion transporter 1 (OAT1) in proximal tubule cells after ischemia and reperfusion, resulting in impairment of PAH clearance. In the present study, we characterized renal OAT1 in detail after ischemia-reperfusion using a rat model. We analyzed renal OAT1 using confocal microscopy with a three-dimensional reconstruction of serial optical images, Western blot, and quantitative real-time RT-PCR. OAT1 was distributed to basolateral membranes of proximal tubule cells in controls. With ischemia, OAT1 decreased in basolateral membrane, especially in the lateral membrane domain, and appeared diffusely in cytoplasm. After reperfusion following 60-min ischemia, OAT1 often formed cytoplasmic aggregates. The staining for OAT1 started reappearing in lateral membrane domain 1 h after reperfusion. The basolateral membrane staining was relatively well discernable at 240 h of reperfusion. Of note, a distinct increase in OAT1 expression was noted in vasculature early after ischemia and after reperfusion. The total amount of OAT1 protein expression in the kidney diminished after ischemia-reperfusion in a duration-dependent manner until 72 h, when they began to recover. However, even at 240 h, the amount of OAT1 did not reach control levels. The kidney tissues tended to show a remarkable but transient increase in mRNA expression for OAT1 at 5 min of ischemia. Our findings may provide insights of renal OAT1 in its cellular localization and response during ischemic acute kidney injury and recovery from it.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Urea Nitrogen
  • Creatinine / blood
  • Ischemia / physiopathology*
  • Kidney Cortex / cytology
  • Kidney Cortex / physiology
  • Kidney Medulla / cytology
  • Kidney Medulla / physiology
  • Kidney Tubules / cytology
  • Kidney Tubules / physiology*
  • Male
  • Organic Anion Transporters, Sodium-Independent / genetics
  • Organic Anion Transporters, Sodium-Independent / metabolism*
  • Polymerase Chain Reaction
  • Rats
  • Rats, Sprague-Dawley
  • Renal Circulation / physiology*
  • Reperfusion


  • Organic Anion Transporters, Sodium-Independent
  • Slco1a1 protein, rat
  • Creatinine