Hypoxia-induced amphiphiles inhibit renal Na+, K(+)-ATPase.

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 beta-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 microM). The present data suggest that amphiphile accumulation may have a potential pathophysiologic role in the proximal tubule during renal ischemia.

• Authors: M Schonefeld, S Noble, A M Bertorello, L J Mandel, M H Creer, D Portilla
• Journal: Kidney international (Kidney Int) Vol. 49 Issue 5 Pg. 1289-96 (May 1996) ISSN: 0085-2538 [Print] United States
• PMID: 8731093 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Fatty Acids
• Lysophosphatidylcholines
• Lysophospholipids
• lysoplasmalogens
• Sodium-Potassium-Exchanging ATPase
• Carnitine

Topics

• Animals
• Carnitine (metabolism, pharmacology)
• Dogs
• Fatty Acids (metabolism)
• Hypoxia (metabolism)
• In Vitro Techniques
• Ischemia (metabolism)
• Kidney (blood supply, metabolism)
• Kidney Tubules, Proximal (metabolism)
• Lysophosphatidylcholines (metabolism, pharmacology)
• Lysophospholipids (metabolism, pharmacology)
• Rabbits
• Sharks
• Sodium-Potassium-Exchanging ATPase (antagonists & inhibitors)