TY - JOUR
T1 - 12S-Lipoxygenase is necessary for human vascular smooth muscle cell survival
AU - Weisinger, G.
AU - Grafi-Cohen, M.
AU - Hirsh, M.
AU - Knoll, E.
AU - Sharon, O.
AU - Many, A.
AU - Limor, R.
AU - Stern, N.
PY - 2013/6/10
Y1 - 2013/6/10
N2 - 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.
AB - 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.
KW - Apoptosis
KW - Baicalein
KW - Human
KW - Lipoxygenase
KW - Smooth-muscle
UR - http://www.scopus.com/inward/record.url?scp=84877925223&partnerID=8YFLogxK
U2 - 10.1016/j.yexcr.2013.04.001
DO - 10.1016/j.yexcr.2013.04.001
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AN - SCOPUS:84877925223
VL - 319
SP - 1586
EP - 1593
JO - Experimental Cell Research
JF - Experimental Cell Research
SN - 0014-4827
IS - 10
ER -