Role of protein kinase C in the control of vascular prostacyclin: Study of phorbol esters effect in bovine aortic endothelium and smooth muscle

Demolle, Dominique; Boeynaems, Jean‐Marie

doi:10.1016/0090-6980(88)90091-3

Cited by 26 publications

(10 citation statements)

References 46 publications

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“…Since activation ofprotein kinase C inhibits phospholipase C, the release of calcium mobilizing inositol triphosphate in response to receptor stimulation may be limited (9,19). Although no attempts were made in these experiments to directly assess the activation by PMA of protein kinase C in intact aortic endothelial cells, previous studies in cultured endothelial cells have demonstrated protein kinase C activation by phorbol ester (6,20).…”

Section: Resultsmentioning

confidence: 80%

Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C.

Tesfamariam¹,

Brown²,

Cohen³

1991

J. Clin. Invest.

408

216

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A possible relationship between protein kinase C activation and impaired receptor-mediated endothelium-dependent relaxation in diabetes mellitus was examined in isolated aorta from normal rabbit exposed to elevated glucose. Aorta treated for 10 min with 4-phorbol 12-myristate 13-acetate (PMA), a protein kinase C activator, showed decreased relaxations to the endothelium-dependent vasodilator, acetylcholine, similar to normal aorta exposed to elevated glucose (22 and 44 mM) for 6 h. Relaxations to the receptor-independent endothelium-dependent vasodilator, A23187, and those caused by the direct smooth muscle vasodilator, sodium nitroprusside, were unaffected by treatment with PMA or exposure to elevated glucose. Indomethacin increased relaxations to acetylcholine of aorta treated with PMA indicating a role for vasoconstrictor prostanoids. PMA caused a significant increase in basal and acetylcholine-stimulated release of vasoconstrictor prostanoids including thromboxane A2 from aortic segments with, but not without endothelium. Protein kinase C inhibitors, H-7 or sphingosine, restored the abnormal acetylcholine-induced relaxations as well as suppressed the abnormal release of prostanoids in aorta exposed to elevated glucose. These findings suggest that the dysfunction ofreceptor-mediated endotheliumdependent relaxation associated with exposure to elevated glucose is due to increased production of vasoconstrictor prostanoids by the endothelium as a consequence of protein kinase C activation. (J. Clin. Invest. 1991. 87:1643-1648

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Section: Resultsmentioning

confidence: 80%

Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C.

Tesfamariam¹,

Brown²,

Cohen³

1991

J. Clin. Invest.

408

216

View full text Add to dashboard Cite

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“…A regulatory role for protein kinase C on phospholipase A, activity has been hypothesized based on observations in several cell types that stimulation of protein kinase C by tumor-promoting phorbol esters such as PMA greatly enhances Ca2 + ionophore-induced arachidonic acid release and metabolism (Frye and Holz, 1985;Halenda et al, 1985;Mobley and Tai, 1985;McColl et al, 1986;Halenda and Rehm, 1987;Demolle and Boeynaems, 1988;Halldorsson et al, 1988;Jeremy and Dandona, 1987). In these studies the enhancing effect of PMA was attributed to its direct stimulation of' protein kinase C, a known effect of PMA (Blumberg et al, 1984).…”

Section: Discussionmentioning

confidence: 99%

“…by raising intracellular free Ca2+ and thereby activating phospholipase A, (Hong et al, 1985;Jaffe et al, 1987;Demolle and Boeynaems, 1988;Rosenthal and Jones, 1988;Whatley et al 1989). In addition to an increase in intracellular Ca,', activation of protein kinase C is also considered an important step in the expression of various cellular functions, including degranulation and secretion in polymorphonuclear leukocytes and platelets.…”

mentioning

confidence: 99%

Enhancement of thrombin‐ and lonomycin‐stimulated prostacyclin and platelet‐activating factor production in cultured endothelial cells by a tumor‐promoting phorbol ester

Zavoico

Hrbolich

Gimbrone

et al. 1990

Journal Cellular Physiology

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Tumor-promoting phorbol esters such as 4 beta-phorbol 12-myristate 13-acetate (PMA) have been shown to act synergistically with Ca2+ ionophores in cell activation, including stimulation of arachidonic acid metabolism. The effects of PMA on unstimulated and Ca2+ ionophore- or thrombin-stimulated PGI2 and platelet-activating factor (PAF) production in cultured bovine aortic endothelial cells (BAEC) and human umbilical vein endothelial cells (HUVEC) were investigated. Incubation of BAEC or HUVEC for 5-10 min with 100 nM PMA alone slightly increased basal PGI2 production. PGI2 production was rapidly stimulated in BAEC and HUVEC treated with the Ca2+ ionophore ionomycin. Preincubation of BAEC or HUVEC with 100 nM PMA for 5-10 min followed by ionomycin for up to 60 min enhanced PGI2 production up to 2.5-fold. Pretreatment with 100 nM PMA for 5 min also caused a 2-fold enhancement of thrombin-stimulated (1 U/ml) PGI2 production in HUVEC. The production of other prostaglandins, PGF2 alpha, PGE2, and PGD2, was also enhanced. In contrast, PMA had no effect on PGI2 synthesized directly from exogenous arachidonic acid or PGH2. The inactive phorbol ester 4 alpha-phorbol 12,13-didecanoate was without effect. Since the biosyntheses of both PGI2 and PAF share a common first step, the hydrolysis of their respective phospholipid precursors by phospholipase A2, we investigated whether PMA preincubation could also enhance PAF biosynthesis. Incubation of HUVEC with 100 nM PMA alone had a negligible effect on PAF production. However, thrombin-stimulated (1 U/ml) PAF production was enhanced 2.6-fold by preincubation with 100 nM PMA. The protein kinase C inhibitors H-7 and staurosporine ablated the enhancing effect of PMA on thrombin-stimulated PGI2 and PAF biosynthesis. These results demonstrate that PMA can significantly alter the production of PGI2 and PAF in vascular endothelial cells, and suggest that protein kinase C activation modulates phospholipase A2 activity in this cell type.

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“…Thrombin stimulates only PG12 production in human umbilical vein EC (Jaffe et al, 1987;Bartha et al, 1989). A23187 stimulates PG12 production in EC from most sources (Clark et al, 1986;Demolle and Boeynaems, 1988;Moore et al, 1988), but does not universally increase EC production of IPS (Derian and Moskowitz, 1986;Moscat et al, 1988).…”

mentioning

confidence: 99%

Receptor‐Linked Hydrolysis of Phosphoinositides and Production of Prostacyclin in Cerebral Endothelial Cells

Moore

et al. 1992

Journal of Neurochemistry

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The receptor agonist-mediated hydrolysis of phosphoinositides and production of prostacyclin were studied in murine cerebral endothelial cells (MCEC). Of 11 neurotransmitters and neuromodulators examined, carbachol, noradrenaline (NE), bradykinin, and thrombin significantly increased 3H-inositol phosphate accumulation in the presence of LiCl (20 mM). The maximal stimulation of [3H]inositol monophosphate ([3H]IP1) reached approximately 11, 11, seven, and four times the basal levels for carbachol, NE, bradykinin, and thrombin, respectively. The EC50 values of IP1 accumulation for carbachol and NE were 34 and 0.16 microM, respectively. The muscarinic antagonists, atropine and pirenzepine, blocked the carbachol-induced IP1 accumulation with Ki values of 0.3 and 30 nM, respectively. The adrenergic antagonist, prazosin, blocked NE-induced IP1 accumulation with a Ki of 0.1 nM. The calcium ionophore A23187, histamine, glutamate, vasopressin, serotonin, platelet activating factor, and substance P did not stimulate IP1 accumulation. A23187, bradykinin, and thrombin stimulated prostacyclin release to approximately four, four, and two times the basal levels, respectively, whereas carbachol and NE had little effect upon prostacyclin release. These results suggest that the activation of phospholipase C and of phospholipase A2 in MCEC are regulated separately.

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Role of protein kinase C in the control of vascular prostacyclin: Study of phorbol esters effect in bovine aortic endothelium and smooth muscle

Cited by 26 publications

References 46 publications

Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C.

Elevated glucose impairs endothelium-dependent relaxation by activating protein kinase C.

Enhancement of thrombin‐ and lonomycin‐stimulated prostacyclin and platelet‐activating factor production in cultured endothelial cells by a tumor‐promoting phorbol ester

Receptor‐Linked Hydrolysis of Phosphoinositides and Production of Prostacyclin in Cerebral Endothelial Cells

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