Generation of Arachidonic Acid and Diacylglycerol Second Messengers from Polyphosphoinositides in Ischemic Fetal Brain

1992 ◽  
Vol 59 (5) ◽  
pp. 1812-1819 ◽  
Author(s):  
Baruch Kunievsky ◽  
Nicolas G. Bazan ◽  
Ephraim Yavin
1991 ◽  
Vol 274 (2) ◽  
pp. 339-347 ◽  
Author(s):  
J M Sontag ◽  
D Thierse ◽  
B Rouot ◽  
D Aunis ◽  
M F Bader

The role of GTP-binding proteins (G-proteins) in the secretory process in chromaffin cells was investigated by studying the effects of pertussis toxin (PTX) on catecholamine release and generation of various second messengers. PTX was found to stimulate the catecholamine secretion induced by nicotine, 59 mM-K+ or veratridine. PTX also potentiated Ca2(+)-evoked catecholamine release from permeabilized chromaffin cells, suggesting that PTX substrate(s) regulate the exocytotic machinery at a step distal to the rise in intracellular Ca2+. We have investigated the possible intracellular pathways involved in the stimulation of secretion by PTX. PTX did not modify the translocation of protein kinase C (PKC) to membranes in intact or permeabilized cells; in addition, neither inhibitors nor activators of PKC had any effect on catecholamine release induced by PTX. Thus it seems unlikely that the effect of PTX on secretion is mediated by activation of PKC. The effect of PTX is also cyclic AMP-independent, as PTX did not change cytoplasmic cyclic AMP levels. The relationship between PTX treatment and arachidonic acid release was also examined. We found that an increase in cytoplasmic arachidonic acid concentration enhanced Ca2(+)-evoked catecholamine release in permeabilized cells, but arachidonic acid did not mimic the effect of PTX on the Ca2(+)-dose-response curve for secretion. Furthermore, PTX did not significantly modify the release of arachidonic acid measured in resting or stimulated chromaffin cells, suggesting that the stimulatory effect of PTX on secretion is not mediated by an activation of phospholipase A2. Taken together, these results suggest that PTX may modulate the intracellular machinery of secretion at a step distal to the generation of second messengers. In alpha-toxin-permeabilized cells, full retention of the PTX-induced activation of secretion was observed even 30 min after permeabilization. In contrast, when chromaffin cells were permeabilized with streptolysin-O (SLO), there was a marked progressive loss of the PTX effect. We found that SLO caused the rapid leakage of three G-protein alpha-subunits which are specifically ADP-ribosylated by PTX. We propose that a PTX-sensitive G-protein may play an inhibitory role in the final stages of the Ca2(+)-evoked secretory process in chromaffin cells.


1995 ◽  
Vol 269 (2) ◽  
pp. C341-C348 ◽  
Author(s):  
B. Soliven ◽  
N. Wang

Arachidonic acid (AA) and its metabolites play a dual role as intracellular second messengers and as transcellular mediators of neural activity. We have previously shown that AA increases cytosolic Ca2+ in oligodendrocytes. In this work, we studied the effects of AA and other fatty acids on whole cell K+ currents of cultured rat oligodendrocytes using the patch-clamp technique. We found that 1) AA decreased the current amplitudes of both the inwardly rectifying K+ current (IKir) and the outward K+ currents (IKo) resulting in membrane depolarization; 2) AA also induced IKo current inactivation/blocked state; 3) AA appeared to act directly on K+ channels and not indirectly via its metabolic products, activation of protein kinase C, or by generation of oxygen free radicals. We have thus demonstrated an additional mechanism for AA-induced signaling in oligodendrocytes, i.e., via modulation of K+ conductances leading to membrane depolarization. The latter has been shown to influence protein phosphorylation and perhaps other important functional output of oligodendrocytes.


1992 ◽  
Vol 21 ◽  
pp. S7
Author(s):  
E. Yavin ◽  
B. Kunievsky ◽  
S. Harel

2000 ◽  
Vol 347 (3) ◽  
pp. 719-724 ◽  
Author(s):  
Amanda E. LEONARD ◽  
Bruce KELDER ◽  
Emil G. BOBIK ◽  
Lu-Te CHUANG ◽  
Jennifer M. PARKER-BARNES ◽  
...  

Two human expressed sequence tag (EST) cDNA sequences with identity with ∆5- and ∆6-desaturases from a filamentous fungus, Mortierella alpina, were identified from the LifeSeq® database of Incyte Pharmaceuticals, Inc. (Palo Alto, CA, U.S.A.). An oligonucleotide complementary to the 3ʹ EST cDNA sequences was used to screen human liver cDNA using rapid amplification of cDNA ends (RACE)-PCR. The amplified DNA fragment had 98% identity with a putative open reading frame (ORF) predicted from a human genomic sequence, and encoded 444 amino acids. Expression of this ORF in mouse fibroblast cells demonstrated that the encoded protein was a ∆5-desaturase, as determined by the conversion of dihomo-γ-linolenic acid (C20:3,n-6) into arachidonic acid (C20:4,n-6). The human ∆5-desaturase contained a predicted N-terminal cytochrome b5-like domain, as well as three histidine-rich domains. A tissue expression profile revealed that this gene is highly expressed in fetal liver, fetal brain, adult brain and adrenal gland. A search of the existing databases led to localization of this ORF within a 14 kb interval flanked by the flap endonuclease-1 (FEN1) and vitelliform macular dystrophy (Best's disease; VMD2) loci of chromosome 11q12.


1989 ◽  
Vol 559 (1 Arachidonie A) ◽  
pp. 248-258 ◽  
Author(s):  
E. YAVIN ◽  
E. GOLDIN ◽  
E. MAGAL ◽  
A. TOMER ◽  
S. HAREL

Nature ◽  
1987 ◽  
Vol 328 (6125) ◽  
pp. 20-20 ◽  
Author(s):  
Stuart Bevan ◽  
John N. Wood

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 734-734
Author(s):  
Michael Crawford ◽  
Mark Johnson ◽  
Yiqun Wang ◽  
David Edwards ◽  
Nora Tusor ◽  
...  

Abstract Objectives To establish why prenatal brain growth in male fetuses responded to an omega-3-rich supplement but the females did not. Methods In a study of maternal lipid status during pregnancy in relation to regional fetal brain development a supplement containing long chain polyenoic fatty acids (300 mg of docosahexaenoic acid DHA, 42 mg eicosapentaenoic (EPA), 8.4 mg arachidonic and placebo 721 mg of oleic acid). Magnetic resonance images were obtained of newborn brains. Quantitative analysis of regions of the brain showed the supplement enhanced brain volume, with and without CSF, cortex, whole grey matter, and corpus callosum but only boys. Results We wish to report correlations for arachidonic and stearic acids with several regions of brain growth in girls but not boys: for example, maternal RBC stearic acid at recruitment correlated with whole cortex (0.85 p < 0.0002), grey matter (0.847 p < 0.0002), corpus callosum (0.699 p < 0.008), whole brain (0.792 p < 0.001), brain plus CSF (0.733 p < 0.004, n = 13). Correlations with arachidonic acid at delivery reflected its index of arachidonic biomagnification and linoleic bioreduction. This measure of placental efficiency for arachidonic was for cortex (0.748 p < 0. 0034), deep grey matter (0.659 p < 0.014), whole grey matter (0.753 p < 0.003), hippocampus (0.611 p < 0.03), lentiform (0.774 p < 0.002), thalami (0.654 p < 0.015), corpus callosum (0.640 p < 0.018), brain (0.685 p < 0.0098), brain with CSF (0.774 p < 0.0019 n = 12). None were seen with the placebo boys (n = 22). Following embryogenesis, the placenta develops ahead of the demands of fetal growth. The fetal cardiovascular system is required to develop to support organogenesis and the brain growth thrust. The fetal immune system is required to help maintain pregnancy and for birth. All these systems are rich in arachidonic acid with little omega 3. The placenta biomagnifies arachidonic acid for the fetus: (typically maternal plasma lecithin 8.76% ± 1.49 CFD fetal cord 17.5% ± 3.22 p < 0.0001 (n = 44), whereas DHA in the same mothers was 4.13% ± 0.98 vs 5.79% ± 1.69 p < 0.0001. Conclusions We conclude that arachidonic acid is playing an as yet, unseen role, and female physiology is more focused on arachidonic acid to serve the basics of reproduction. Funding Sources The Mother and Child Foundation, Waterloo Foundation and the BORNE Charity.


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