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Linoleic acid epoxide promotes the maintenance of mitochondrial function and active Na+ transport following hypoxia.

Abstract
Low concentrations of arachidonic acid monoepoxides protect against ischemia/reperfusion injury. This study examined whether low concentrations of the linoleic acid monoepoxide, cis-12,13-epoxy-9-octadecenoic acid (12,13-EOA), protect renal cells against decreases in mitochondrial and transport functions induced by hypoxia/reoxygenation. Primary cultures of rabbit renal proximal tubular cells (RPTC) were pretreated with diluent or 1, 5, or 10 microM 12,13-EOA for 1 h and exposed to 2 h hypoxia/0.5 h reoxygenation in the absence of 12,13-EOA. Basal respiration, oligomycin-sensitive oxygen consumption (QO2), and ATP content decreased 31, 35 and 65%, respectively, following hypoxia/reoxygenation. Hypoxia/reoxygenation also increased mitochondrial membrane potential (DeltaPsi(m)). Pretreatment with 12,13-EOA prevented decreases in basal and oligomycin-sensitive QO2s and increases in DeltaPsi(m). Despite the protection against decreases in mitochondrial function, 12,13-EOA pretreatment did not prevent the initial decrease in intracellular ATP content following hypoxia. However, pretreatment did accelerate the recovery of intracellular ATP levels during reoxygenation. Pretreatment with 12,13-EOA also prevented hypoxia-induced decreases in active Na+ transport. Ouabain-sensitive QO2 (a marker of active Na+ transport) decreased 38% following hypoxia/reoxygenation but was maintained in RPTC pretreated with 1, 5 or 10 microM 12,13-EOA prior to hypoxia. Pretreatment of RPTC with the hydrolyzed product of 12,13-EOA, 12,13-dihydroxyoctadecenoic acid, did not have any protective effects against mitochondrial dysfunction and decreases in active Na+ transport. Thus, this is the first report demonstrating that preconditioning of RPTC with low concentrations of 12,13-EOA, but not its hydrolyzed product, maintains mitochondrial respiration, accelerates restoration of ATP levels, and prevents decreases in active Na+ transport following hypoxia/reoxygenation.
AuthorsGrazyna Nowak, David F Grant, Jeffery H Moran
JournalToxicology letters (Toxicol Lett) Vol. 147 Issue 2 Pg. 161-75 (Mar 01 2004) ISSN: 0378-4274 [Print] Netherlands
PMID14757320 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S., Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • 12,13-epoxy-9-octadecenoic acid
  • Fluorescent Dyes
  • Linoleic Acids
  • Oleic Acids
  • Adenosine Triphosphate
  • Sodium
  • L-Lactate Dehydrogenase
  • Proton-Translocating ATPases
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Biological Transport, Active
  • Cell Hypoxia (physiology)
  • Cells, Cultured
  • Female
  • Fluorescent Dyes
  • Hypoxia (metabolism)
  • Kidney Tubules, Proximal (cytology, drug effects, metabolism)
  • L-Lactate Dehydrogenase (metabolism)
  • Linoleic Acids (pharmacology)
  • Membrane Potentials (drug effects)
  • Mitochondria (drug effects, metabolism)
  • Oleic Acids (chemical synthesis, pharmacology)
  • Oxygen Consumption (drug effects)
  • Proton-Translocating ATPases (metabolism)
  • Rabbits
  • Sodium (metabolism)

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