Hypoxia-induced amphiphiles inhibit renal Na+,K+-ATPase

Michael Schonefeld, Shevonya Noble, Alejandro M. Bertorello, Lazard J. Mandel, Michael H. Creer, Didier Portilla

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25 Scopus citations

Abstract

We have characterized the effects of hypoxia on carnitine metabolism in proximal tubules. Hypoxia for 10 minutes resulted in a significant increase in the mass of long chain acylcarnitines (LCAC) (control 53 ± 20 vs. hypoxia 118 ± 38 pmol·mg-1 protein). Since LCAC are proximal metabolites in the β-oxidation of fatty acids, these data suggest that inhibition of fatty acid oxidation occurs during hypoxia in the proximal tubule. In addition to LCAC accumulation, hypoxia resulted in a significant increase in the mass of lysoplasmenylcholine LPLasCho (control 62 ± 15 pmol/mg vs. 20 min hypoxia 146 ± 21 pmol/mg protein, N = 4) and also in increases in the mass of monoacyl LPC (control 122 ± 24 pmol/mg protein vs. 283 ± 35 pmol/mg protein after 40 min of hypoxia). We tested the possibility that these compounds that accumulate during hypoxia could inhibit proximal tubule Na+,K+-ATPase. LPC, LPlasC, and LCAC inhibited proximal tubule nystatin-stimulated oxygen consumption (QO2) and proximal tubule Na+,K+-ATPase activity in a dose-dependent manner. In addition, LPC, LPlasC, and LCAC directly inhibited (65%, 80%, and 60%, respectively) Na+,K+-ATPase activity purified from kidney cortex at similar concentrations at which they accumulate during hypoxia (above 25 μM). The present data suggest that amphiphile accumulation may have a potential pathophysiologic role in the proximal tubule during renal ischemia.

Original languageEnglish (US)
Pages (from-to)1289-1296
Number of pages8
JournalKidney International
Volume49
Issue number5
DOIs
StatePublished - Jan 1 1996

All Science Journal Classification (ASJC) codes

  • Nephrology

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    Schonefeld, M., Noble, S., Bertorello, A. M., Mandel, L. J., Creer, M. H., & Portilla, D. (1996). Hypoxia-induced amphiphiles inhibit renal Na+,K+-ATPase. Kidney International, 49(5), 1289-1296. https://doi.org/10.1038/ki.1996.184