Polyphosphoinositides as a Probable Source of Brain Free Fatty Acids Accumulated at the Onset of Ischemia

Masuhiro Ikeda, Shinichi Yoshida, Raul Busto, Mercedes Santiso, Myron D. Ginsberg

Research output: Contribution to journalArticle

143 Scopus citations

Abstract

The quantitative relationship between phosphoinositides and free fatty acids (FFAs) in brain ischemia was studied by measuring contents of individual fatty acids in phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol (PI), phosphatidic acid (PA), diacylglycerol (DAG), and the FFA pool. Various periods of complete ischemia (1, 3, 10, and 30 min) were produced by decapitation. Ischemia of 1-3 min caused rapid decreases in PIP2 and PIP content together with preferential production of stearic and arachidonic acids in the DAG and FFA pools. The decrement in levels of these fatty acid residues in polyphosphoinositides was sufficient to account for their increment in levels in the enlarged DAG and FFA pools. After 10 min of ischemia, levels of PIP2, PIP, and DAG approached plateau values, but levels of all FFAs continued to increase. The increases in content of DAG and FFAs at later ischemic periods could not be accounted for by the decreases in content of PIP2 and PIP. PI and PA levels showed only transient and subtle changes. These results indicate that, at the onset of ischemia, phosphodiesteric cleavage of PIP2 and PIP subsequent deacylation by lipases are primarily responsible for the preferential increase in levels of free stearic and arachidonic acids and that, later, hydrolysis of other phospholipids plays a major role in the continuous accumulation of FFAs.

Original languageEnglish (US)
Pages (from-to)123-132
Number of pages10
JournalJournal of neurochemistry
Volume47
Issue number1
DOIs
StatePublished - Jul 1986

Keywords

  • Brain ischemia
  • Diacylglycerol
  • Free fatty acids
  • Polyphosphoinositides
  • Rat brain

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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