Possible involvement of direct stimulation of protein kinase c by unsaturated fatty acids in platelet activation

1988 ◽  
Vol 37 (16) ◽  
pp. 3079-3089 ◽  
Author(s):  
Masakatsu Nishikawa ◽  
Hiroyoshi Hidaka ◽  
Shigeru Shirakawa
Keyword(s):  
Fatty Acids ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Unsaturated Fatty Acids ◽  
Direct Stimulation ◽  
Kinase C ◽  
Stimulation Of

scholarly journals Direct stimulation of protein kinase C by arachidonate is associated with platelet activation.

1987 ◽  
Vol 18 (2) ◽  
pp. 138-141
Author(s):  
Masakatsu NISHIKAWA ◽  
Yasuhiro UEMURA ◽  
Hideo WADA ◽  
Katsumi DEGUCHI ◽  
Shigeru SHIRAKAWA
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Direct Stimulation ◽  
Kinase C ◽  
Stimulation Of

Rat histidine decarboxylase promoter is regulated by gastrin through a protein kinase C pathway

1996 ◽  
Vol 270 (4) ◽  
pp. G619-G633 ◽  
Author(s):  
M. Hocker ◽  
Z. Zhang ◽  
D. A. Fenstermacher ◽  
S. Tagerud ◽  
M. Chulak ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Time Course ◽  
Histidine Decarboxylase ◽  
Peptide Hormone ◽  
Direct Stimulation ◽  
Gastric Glands ◽  
Kinase C ◽  
Translational Start ◽  
Stimulation Of

The enzyme L-histidine decarboxylase (HDC; EC 4.1.1.22), which converts L-histidine to histamine, plays a key role in the regulation of acid secretion. In the rat and human stomach, the peptide hormone gastrin appears to be one of the main regulators of HDC expression. In rats, marked elevation of gastric HDC mRNA abundance was observed within 12 h after induction of hypergastrinemia by a single injection of the proton-pump blocker omeprazole. In situ hybridization revealed that HDC expression occurred in the basal third of gastric glands where enterochromaffin-like cells are localized. To study the regulation of HDC gene transcription, 1,291 nucleotides of the 5'-flanking region of the rat HDC gene and the noncoding portion of exon 1 were cloned and sequenced. Gastrin and cholecystokinin (CCK) octapeptide equipotently stimulated the transcriptional activity of the rat HDC promoter three- to fourfold, and deletion analysis revealed the presence of a gastrin response element within 201 nucleotides upstream of the translational start site. Time-course studies revealed maximal activation of the HDC promoter after 12-36 h. Direct stimulation of protein kinase C (PKC) with the phorbol ester phorbol 12-myristate 13-acetate (PMA) substantially elevated rat HDC promoter activity, whereas induction of Ca2+ -dependent signaling pathways with thapsigargin was without effect. Downregulation or blockade of PKC abolished the effects of gastrin and PMA on the HDC promoter. These data indicate that stimulation of the CCK-B/gastrin receptor activates the rat HDC promoter in a time- and dose-dependent fashion and that this effect is primarily mediated via a PKC-dependent signaling pathway. Use of HDC as a model gene will allow further investigation of the intracellular pathways that are involved in gastrin-dependent gene regulation.

Adenosine A1 receptor-mediated inhibition of myocardial norepinephrine release involves neither phospholipase C nor protein kinase C but does involve adenylyl cyclase

2006 ◽  
Vol 84 (5) ◽  
pp. 573-577 ◽  
Author(s):  
Frank Schütte ◽  
Christof Burgdorf ◽  
Gert Richardt ◽  
Thomas Kurz
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Adenylyl Cyclase ◽  
Phospholipase C ◽  
Suppressive Effect ◽  
Inhibitory Effect ◽  
Direct Stimulation ◽  
Kinase C ◽  
Gf 109203X ◽  
Stimulation Of

Stimulation of adenosine A1 receptors in the heart exerts cardioprotective effects by inhibiting norepinephrine (NE) release from sympathetic nerve endings. The intraneuronal signal transduction triggered by presynaptic adenosine A1 receptors is still not completely understood. The objective of the present study was to determine whether phospholipase C (PLC), protein kinase C (PKC), and adenylyl cyclase (AC) are involved in the adenosine A1 receptor-mediated inhibition of endogenous (stimulation-induced) NE release in isolated Langendorff-perfused rat hearts as an approach to elucidate their role in the cardiovascular system. Activation of adenosine A1-receptors with 2-chloro-N6-cyclopentyladenosine (CCPA) decreased cardiac NE release by ~40%. Inhibition of PLC with 1-[6-[[(17b)-3-methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione (U 73122) as well as inhibition of PKC with 2-[1-(3-dimethylaminopropyl)indol-3-yl]-3-(indol-3-yl)maleimide (GF 109203X) slightly but significantly decreased NE release; however, the suppressive effect of CCPA on NE release was not modulated by U 73122 or GF 109203X. Blockade of AC with 9-(tetrahydro-2′-furyl)adenine (SQ 22536) reversed the inhibitory effect of CCPA on sympathetic neurotransmitter release irrespective of whether PKC was pharmacologically activated by phorbol 12-myristate 13-acetate or was not activated, indicating a PKC-independent but AC-dependent mechanism. Direct stimulation of AC with forskolin increased NE release by ∼20%; an effect that was antagonized by either CCPA or SQ 22536. These data suggest that the adenosine A1 receptor-mediated inhibition of NE release does not involve PLC or PKC but does involve AC.

scholarly journals Cytoplasmic lipid bodies of neutrophils: formation induced by cis-unsaturated fatty acids and mediated by protein kinase C.

1991 ◽  
Vol 113 (1) ◽  
pp. 137-146 ◽  
Author(s):  
P F Weller ◽  
S W Ryeom ◽  
S T Picard ◽  
S J Ackerman ◽  
A M Dvorak
Keyword(s):  
Fatty Acids ◽  
Protein Kinase C ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Unsaturated Fatty Acids ◽  
Lipid Body ◽  
Lipid Bodies ◽  
Myristate Acetate ◽  
Body Formation ◽  
Kinase C

Lipid bodies, nonmembrane-bound cytoplasmic inclusions, serve as repositories of esterified arachidonate and are increased in cells associated with inflammatory reactions. We have evaluated stimuli and mechanisms responsible for lipid body formation within human polymorphonuclear leukocytes (PMNs). Arachidonic acid and oleic acid stimulated dose-dependent formation of lipid bodies over 0.5-1 h. Other C20 and C18 fatty acids were less active and demonstrated rank orders as follows: cis-unsaturated fatty acids were much more active than trans-fatty acids, and activity diminished with decreasing numbers of double bonds. Lipid bodies elicited in vitro with cis-fatty acids were ultrastructurally identical to lipid bodies present in PMNs in vivo. Lipid body induction was not because of fatty acid-elicited oxidants or fatty acid-induced ATP depletion. Cis-fatty acid-induced activation of protein kinase C (PKC) was involved in lipid body formation as evidenced by the capacity of other PKC activators, 1-oleoyl-2-acetyl-glycerol and two active phorbol esters, phorbol myristate acetate, and phorbol 12,13 dibutyrate, but not an inactive phorbol, to induce lipid body formation. The PKC inhibitor, 1-O-hexadecyl-2-O-methyl-glycerol, inhibited PMN lipid body formation induced by oleic and arachidonic acids and by 1-oleoyl-2-acetyl-glycerol and phorbol myristate acetate. Other PKC inhibitors (staurosporine, H-7) also inhibited lipid body formation. Formation of lipid bodies in PMNs is a specific cellular response, stimulated by cis-fatty acids and diglycerides and apparently mediated by PKC, which results in the mobilization and deposition of lipids within discrete, ultrastructurally defined cytoplasmic domains.

scholarly journals Calcium-Independent Activation of Hypothalamic Type I Protein Kinase C by Unsaturated Fatty Acids

1988 ◽  
Vol 2 (11) ◽  
pp. 1043-1048 ◽  
Author(s):  
Zvi Naor ◽  
Mark S. Shearman ◽  
Akira Kishimoto ◽  
Yasutomi Nishizuka
Keyword(s):  
Fatty Acids ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Unsaturated Fatty Acids ◽  
Type I ◽  
Kinase C

DAG accumulation from saturated fatty acids desensitizes insulin stimulation of glucose uptake in muscle cells

2001 ◽  
Vol 280 (2) ◽  
pp. E229-E237 ◽  
Author(s):  
Eulàlia Montell ◽  
Marco Turini ◽  
Mario Marotta ◽  
Matthew Roberts ◽  
Véronique Noé ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Protein Kinase C ◽  
Protein Kinase ◽  
Glucose Uptake ◽  
Insulin Response ◽  
Insulin Stimulation ◽  
Kinase C ◽  
Basal Glucose Uptake ◽  
Stimulation Of

The increased availability of saturated lipids has been correlated with development of insulin resistance, although the basis for this impairment is not defined. This work examined the interaction of saturated and unsaturated fatty acids (FA) with insulin stimulation of glucose uptake and its relation to the FA incorporation into different lipid pools in cultured human muscle. It is shown that basal or insulin-stimulated 2-deoxyglucose uptake was unaltered in cells preincubated with oleate, whereas basal glucose uptake was increased and insulin response was impaired in palmitate- and stearate-loaded cells. Analysis of the incorporation of FA into different lipid pools showed that palmitate, stearate, and oleate were similarly incorporated into phospholipids (PL) and did not modify the FA profile. In contrast, differences were observed in the total incorporation of FA into triacylglycerides (TAG): unsaturated FA were readily diverted toward TAG, whereas saturated FA could accumulate as diacylglycerol (DAG). Treatment with palmitate increased the activity of membrane-associated protein kinase C, whereas oleate had no effect. Mixture of palmitate with oleate diverted the saturated FA toward TAG and abolished its effect on glucose uptake. In conclusion, our data indicate that saturated FA-promoted changes in basal glucose uptake and insulin response were not correlated to a modification of the FA profile in PL or TAG accumulation. In contrast, these changes were related to saturated FA being accumulated as DAG and activating protein kinase C. Therefore, our results suggest that accumulation of DAG may be a molecular link between an increased availability of saturated FA and the induction of insulin resistance.

Platelet-activating factor modulates microvascular transport by stimulation of protein kinase C

1994 ◽  
Vol 266 (3) ◽  
pp. H1214-H1220 ◽  
Author(s):  
I. Kobayashi ◽  
D. Kim ◽  
R. W. Hobson ◽  
W. N. Duran
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Platelet Activating Factor ◽  
Cheek Pouch ◽  
Hamster Cheek Pouch ◽  
Direct Stimulation ◽  
Calphostin C ◽  
Kinase C ◽  
Pkc Inhibitors ◽  
Stimulation Of

To investigate the possible involvement of protein kinase C (PKC) in platelet-activating factor (PAF)-stimulated microvascular responses, PKC inhibitors, sphingosine (SPH), 1-(5-isoquino-linylsulfonyl)-3-methylpiperazine (iso H-7), and calphostin C, were applied topically to the hamster cheek pouch, and PAF-elicited changes in microvascular permselectivity and arteriolar constriction were evaluated. Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 significantly reduced 10(-7) M PAF-induced increase in fluorescein isothiocyanate-Dextran 150 clearance (2,677.3 +/- 397.3, 2,985.3 +/- 350.7, and 2,689.3 +/- 256.0 vs. 4,784.0 +/- 474.7 nl.60 min-1.g-1, respectively). Calphostin C at 10(-7) M attenuated 10(-8) M PAF-induced increase in clearance (2,156.9 +/- 353.3 vs. 3,841.6 +/- 260.9 nl.60 min-1.g-1). Permeability changes were also measured by integrated optical intensity (IOI). Pretreatment with 10(-6) M SPH, 10(-5) M SPH, or 10(-10) M iso H-7 attenuated the maximal increment in IOI induced by 10(-7) M PAF (2,024.0 +/- 364.4, 1,690.0 +/- 525.2, and 2,432.8 +/- 655.3 vs. 4,255.9 +/- 695.6 U, respectively). Direct stimulation of PKC by phorbol dibutyrate increased clearance in dose-dependent fashion. Similarly, activation of PKC with phorbol myristate acetate increased IOI values. The PAF-induced arteriolar constriction was not blocked by the PKC inhibitors. Our results suggest that PKC represents a biochemical pathway involved in the PAF modulation of microvascular permeability but not of arteriolar constriction.

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