Histamine increases sphingosine kinase-1 expression and activity in the human arterial endothelial cell line EA.hy 926 by a PKC-alpha-dependent mechanism

Sphingosine 1-phosphate (S1P) is a potent mitogenic signal generated from sphingosine by the action of sphingosine kinases (SKs). In this study, we show that in the human arterial endothelial cell line EA.hy 926 histamine induces a time-dependent upregulation of the SK-1 mRNA and protein expression which is followed by increased SK-1 activity. A similar upregulation of SK-1 is also observed with the direct protein kinase C activator 12-O-tetradecanoylphorbol-13-acetate (TPA). In contrast, SK-2 activity is not affected by neither histamine nor TPA. The increased SK-1 protein expression is due to stimulated de novo synthesis since cycloheximide inhibited the delayed SK-1 protein upregulation. Moreover, the increased SK-1 mRNA expression results from an increased promoter activation by histamine and TPA. In mechanistic terms, the transcriptional upregulation of SK-1 is dependent on PKC and the extracellular signal-regulated protein kinase (ERK) cascade since staurosporine and the MEK inhibitor U0126 abolish the TPA-induced SK-1 induction. Furthermore, the histamine effect is abolished by the H1-receptor antagonist diphenhydramine, but not by the H2-receptor antagonist cimetidine. Parallel to the induction of SK-1, histamine and TPA stimulate an increased migration of endothelial cells, which is prevented by depletion of the SK-1 by small interfering RNA (siRNA). To appoint this specific cell response to a specific PKC isoenzyme, siRNA of PKC-alpha, -delta, and -epsilon were used to selectively downregulate the respective isoforms. Interestingly, only depletion of PKC-alpha leads to a complete loss of TPA- and histamine-triggered SK-1 induction and cell migration. In summary, these data show that PKC-alpha activation in endothelial cells by histamine-activated H1-receptors, or by direct PKC activators leads to a sustained upregulation of the SK-1 protein expression and activity which, in turn, is critically involved in the mechanism of endothelial cell migration.

Rabbinismus enucleatus : quo ad ea, quæ Ebræo-Chaldæis vel prorsus non, vel minus usitata sunt : præmissa directione legendi Scripturam absque punctis

Ioh. Andr. Danz

Maḥazē mekîrat Yôsēf : ein ṭeaṭer šṭik in 7 akṭin un in 17 szenen ; giformirṭ noch di besṭe un gleichsṭe deos fun gemore ...

fun Eljakim Tzunzer

Moris Shṿarts un der Idisher ḳunsṭ ṭeaṭer

A. H. Bialin

Geshikhṭe fun yidisher ṭeaṭer-ḳunsṭ un drame : fun di elṭsṭe tsayṭn biz 1750

Yitsḥaḳ Shiper

Margaret OH̀ea, Brustbild

Signatur des Originals: S 36/F09444

Mus S 21/536 - Costumes aus der Oper "Der Baum der Diana" [L'arbore di Diana], für die EA Frankfurt 12.06.1788

1. Diana, 2. Endimion, 3. Amor, 4. Dorist, 5. Silvio, 6. Silvio als Priester, 7. Nymphe

Ms. lat. oct. 69 - Collegium Institutionum in quo praecipue ad Notas Locamerianas ea quae deficiunt supplentur

Die tatsächliche Foliierung weicht von den Angaben des Kataloges ab.

Secunda pars dictionarij in qua dictio quelibet per literas alphabeti iuxta co[n]gruentia[m] distinguitur vtqua[m] facillime omnia in ea contenta reperia[n]tur co[n]tinetq[ue] dictio[n]es his literis incipientes E, F, G, H, I, K, L, M, N, O / [editu[m] pe

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Imp. tomados del colofón del t. 9

In festo S. Salome Viduae : omnia de communi sanctarum nec Virginum, praeter, ea, quae, sequuntur ..

Precede al tit.: "Die XXII. Octobris."

Copia del Oficio pasado al S[eñ]or Reg[en]te de la R[ea]l Aud[ienci]a y [al] Rector de la Universi[da]d Literaria, sobre la Protectoria del Colegio de los Santos Reyes dicho de Villena [Manuscrito]

Alcance y contenido: Copia ms. sin firmar de un oficio envíado por el Subdelegado en Valencia de la "Colecturía general de espolios y vacantes", ramo Inquisición, organismo creado en Madrid en 1753, unida a la Comisaría general de Cruzada, aunque con función independiente y jurisdicción especial. El Colector General, tenía subdelegados en todas las diócesis. Esta Colecturía se suprimió en 1851. El subdelegado le reclama tanto al Regente de la Real Audiencia de Valencia, como al Rector de la Universidad Literaria la protectoría del Colegio de los Santos Reyes de Villena por ser una institución perteneciente a la Inquisición.

Pius Papa V... Romanus Pontifex ad ea libente intendere consueuit per que quarun libet ciuitatum primum almae urbi propij videlicet domicilij... [Texto impreso]

Precede al tít. : "Ad perpetuam rei memoriam"