Differential phospholipid metabolism in rat aortic smooth muscle cells of varying proliferative potential upon long term exposure to phorbol 12-myristate 13-acetate

Russell C. Bowes, Xiaolan Ou, Kenneth S. Ramos

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Subchronic exposure of rats to allylamine (AAM) modulates aortic smooth muscle cells (SMCs) from a quiescent to a proliferative phenotype. This response is associated with alterations in phospholipid metabolism and protein kinase C (PKC) activity. The present studies were conducted to evaluate the effects of long-term exposure to phorbol 12-myristate 13-acetate (PMA) on phospholipid metabolism in SMCs derived from control and AAM-treated animals, cells of varying proliferative potential. Measurements of 32P/[3H]myristic acid incorporation into parent phospholipids and phosphatidic acid (PA) and the extent of PKC-mediated histone phosphorylation were conducted following exposure of pre- and postconfluent subcultures of SMCs to PMA for 3 h. Increased 32P incorporation into phosphatidylcholine (PC) was observed in both pre- and postconfluent cultures of control and AAM cells treated with PMA relative to vehicle. This response was attenuated in pre- and postconfluent AAM cells relative to control counterparts. PMA enhanced 32P incorporation into phosphatidylinositol (PI) in preconfluent cultures of control cells, but decreased 32P incorporation in cultures of AAM cells relative to vehicle. A similar relationship was observed in the PI profile of postconfluent cultures. The alterations in primary phospholipid profiles induced by PMA correlated with the loss of PKC-mediated histone phosphorylation in the cytosolic and particulate fractions of both cell types. The pattern of 32P incorporation into PA, a phospholipid metabolite, paralleled that of PC in cultures of both cell types. In the presence of ethanol, vehicle-treated control and AAM cells exhibited a modest increase in phosphatidylethanol (PEt) formation, as measured by [3H]myristic acid incorporation. PMA enhanced PEt formation in control and AAM cultures, but selectively decreased [3H]myristic acid incorporation into PA in AAM cells. These data demonstrate that long-term PMA treatment differentially modulates phospholipid metabolism in aortic SMCs of varying proliferative potential. These alterations are associated with modulation of PLD-mediated hydrolysis of membrane phospholipids.

Original languageEnglish (US)
Pages (from-to)213-228
Number of pages16
JournalChemico-Biological Interactions
Volume86
Issue number3
DOIs
StatePublished - Mar 1993
Externally publishedYes

Keywords

  • Allylamine
  • Aortic smooth muscle cells
  • Cell proliferation
  • Phorbol 12-myristate 13-acetate
  • Phospholipid metabolism
  • Protein kinase C

ASJC Scopus subject areas

  • Toxicology

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