12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival

G. Weisinger, M. Grafi-Cohen, M. Hirsh, E. Knoll, O. Sharon, A. Many, R. Limor, N. Stern

Research output: Contribution to journalArticlepeer-review

Abstract

Considerable evidence has been published demonstrating the importance of lipoxygenase enzymes for vascular smooth muscle cell (VSMC) growth. The current study sets out to determine whether or not 12-lipoxygenase (12LO) is also important for human placental VSMC survival. Both a pharmacological and two 12LO antisense knockdown approaches were applied. The 12LO inhibitor baicalien induced a 2-2.5-fold increase in cell death, which appeared to result from apoptosis, as indicated by DNA fragmentation, activation of procaspase 3 to caspase 3 and cytochrome C release from the mitochondria to the cytosol. This apoptosis could be prevented by treatment with the 12LO product, 12 hydroxyeicosatetraenoic acid (12HETE). Human platelet-type 12LO-antisense knockdown, by either plasmid transfection or adeno-associated virus (AAV) infection also induced substantial VSMC death over controls, which could also be prevented by treatment with 12HETE, but not 5HETE. Hence, biochemical 12LO inhibition or 12LO-antisense knockdown in VSMC can induce programmed cell death. These observations suggest a previously unrecognized association between human VSMC survivability and 12LO.

Original languageEnglish
Pages (from-to)1586-1593
Number of pages8
JournalExperimental Cell Research
Volume319
Issue number10
DOIs
StatePublished - 10 Jun 2013

Keywords

  • Apoptosis
  • Baicalein
  • Human
  • Lipoxygenase
  • Smooth-muscle

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