The reduction of Na/H exchanger-3 protein and transcript expression in acute ischemia-reperfusion injury is mediated by extractable tissue factor(s)

Francesca Di Sole, Ming Chang Hu, Jianning Zhang, Victor Babich, I. Alexandru Bobulescu, Mingjun Shi, Paul McLeroy, Thomas E. Rogers, Orson W. Moe

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Ischemic renal injury is a formidable clinical problem, the pathophysiology of which is incompletely understood. As the Na/H exchanger-3 (NHE3) mediates the bulk of apical sodium transport and a significant fraction of oxygen consumption in the proximal tubule, we examined mechanisms by which ischemia-reperfusion affects the expression of NHE3. Ischemia-reperfusion dramatically decreased NHE3 protein and mRNA (immunohistochemistry, immunoblot, and RNA blot) in rat kidney cortex and medulla. The decrease in NHE3 protein was uniform throughout all tubules, including those appearing morphologically intact. In the kidney cortex, a decrease in NHE3 surface protein preceded that of NHE3 total protein and mRNA. Kidney homogenates from rats exposed to mild renal ischemia-reduced cell surface NHE3 protein expression in opossum kidney cells in vitro, whereas homogenates from animals with moderate-to-severe ischemia reduced both total NHE3 protein and mRNA. The decrease in total NHE3 protein was dependent on the proteasomal degradation associated with NHE3 ubiquitylation measured by coimmunoprecipitation. The transferable factor(s) from the ischemic homogenate that reduce NHE3 expression were found to be heat sensitive and to be associated with a lipid-enriched fraction, and did not include regulatory RNAs. Thus, transferable factor(s) mediate the ischemia-reperfusion injury-induced decrease in NHE3 of the kidney.

Original languageEnglish (US)
Pages (from-to)822-831
Number of pages10
JournalKidney international
Volume80
Issue number8
DOIs
StatePublished - Oct 2 2011

Keywords

  • Na transport
  • acute kidney injury
  • epithelial sodium transport
  • ischemia-reperfusion
  • proximal tubule

ASJC Scopus subject areas

  • Nephrology

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