NITRIC-OXIDE ACTIVATES THE GLUCOSE-DEPENDENT MOBILIZATION OF ARACHIDONIC-ACID IN A MACROPHAGE-LIKE CELL-LINE (RAW-264.7) THAT IS LARGELY MEDIATED BY CALCIUM-INDEPENDENT PHOSPHOLIPASE A(2)
Rw. Gross et al., NITRIC-OXIDE ACTIVATES THE GLUCOSE-DEPENDENT MOBILIZATION OF ARACHIDONIC-ACID IN A MACROPHAGE-LIKE CELL-LINE (RAW-264.7) THAT IS LARGELY MEDIATED BY CALCIUM-INDEPENDENT PHOSPHOLIPASE A(2), The Journal of biological chemistry, 270(25), 1995, pp. 14855-14858
Herein, we demonstrate that nitric oxide is a potent (>20% release) an
d highly selective inducer of [H-3]arachidonic acid mobilization in th
e macrophage-like cell line RAW 264.7. Treatment of RAW 264.7 cells wi
th momethylene)-3-(1-naphthalenyl)-2H-tetrahydropyran -2-one resulted
in the inhibition of the large majority (86%) of nitric oxide-induced
[H-3]arachidonic acid release into the medium (IC50 <0.5 mu M) and the
concomitant inhibition of in vitro measurable calcium-independent pho
spholipase A(2) activity (92% inhibition) without demonstrable effects
on calcium-dependent phospholipase A(2) activity. Since nitric oxide
is a potent stimulator of glycolysis (and therefore glycolytically der
ived ATP) and since cytosolic calcium-independent phospholipase A(2) e
xists as a catalytic complex comprised of ATP-modulated phosphofructok
inase-like regulatory polypeptides and a catalytic subunit, we examine
d the role of glucose in facilitating nitric oxide-mediated arachidoni
c acid release. Nitric oxide-induced release of [H-3]arachidonic acid
possessed an obligatory requirement for glucose, was highly correlated
with the concentration of glucose in the medium, and was dependent on
the metabolism of glucose. Thus, [H-3]arachidonic acid release is cou
pled to cellular glucose metabolism through alterations in the activit
y of calcium-independent phospholipase A(2). Collectively, these resul
ts identify a unifying metabolic paradigm in which the generation of l
ipid second messengers is coordinately linked to the signalstimulated
acceleration of glycolytic flux, thereby facilitating integrated metab
olic responses to cellular stimuli.