HOMEPRODUCTSCOMPANYCONTACTFAQResearchDictionaryPharmaSign Up FREE or Login

Reperfusion induces 5-lipoxygenase translocation and leukotriene C4 production in ischemic brain.

Abstract
5-Lipoxygenase (5-LO) converts arachidonic acid, released from membrane phospholipids upon external stimulation, to leukotriene C4 (LTC4), which induces various kinds of cellular and molecular responses. We examined the effects of 5 min of ischemia on brain 5-LO and LTC4 during reperfusion using the gerbil model of transient forebrain ischemia that develops neuronal necrosis selectively in the hippocampus. Neurons exhibited dense 5-LO immunoreactivity; 5-LO was partially redistributed from cytosolic to particulate fractions 3 min during reperfusion. LTC4 was generated in neurons and was increased in all forebrain regions during reperfusion. Postischemic increases in LTC4 were inhomogeneous; a greater increase was observed in the hippocampus (13.37 +/- 0.24 pmol/g tissue) than in the other regions (cerebral cortex: 3.29 +/- 1.09 pmol/g). Superoxide dismutase and dimethylthiourea, oxygen radical scavengers, attenuated the production of LTC4 and damage to the neurons in the hippocampus during reperfusion. Our findings indicated that reperfusion, which was associated with translocation of cytosolic 5-LO to membranes and generation of oxygen radicals, induced the production of LTC4 and suggested that excess LTC4 production may mediate irreversible reperfusion injuries in the hippocampal neurons.
AuthorsT Ohtsuki, M Matsumoto, Y Hayashi, K Yamamoto, K Kitagawa, S Ogawa, S Yamamoto, T Kamada
JournalThe American journal of physiology (Am J Physiol) Vol. 268 Issue 3 Pt 2 Pg. H1249-57 (Mar 1995) ISSN: 0002-9513 [Print] United States
PMID7900879 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Recombinant Proteins
  • Leukotriene C4
  • 1,3-dimethylthiourea
  • Arachidonate 5-Lipoxygenase
  • Superoxide Dismutase
  • Thiourea
Topics
  • Animals
  • Arachidonate 5-Lipoxygenase (metabolism)
  • Brain Ischemia (metabolism, pathology)
  • Cerebral Cortex (injuries, metabolism, pathology)
  • Gerbillinae
  • Hippocampus (injuries, metabolism, pathology)
  • Humans
  • Immunohistochemistry
  • Leukotriene C4 (biosynthesis)
  • Male
  • Necrosis
  • Neurons (metabolism, pathology)
  • Recombinant Proteins (pharmacology)
  • Reperfusion Injury (metabolism, pathology)
  • Superoxide Dismutase (pharmacology)
  • Thiourea (analogs & derivatives, pharmacology)
  • Tissue Distribution

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research graph!


Choose Username:
Email:
Password:
Verify Password:
Enter Code Shown: