title: TPA induction of Epstein-Barr virus early antigens in Raji cells is blocked by selective protein kinase-C inhibitors.
abstract: We have shown that modulation of intracellular calcium in EBV latently infected cells could induce the expression of viral antigens, and suggested that a protein kinase-C (PKC) may play a major role in the EBV genome activation. We now report further investigations on the role of PKC using 2 selective enzymatic inhibitors [1-(5-Isoquinolinylsulfonyl)-2-methylpiperazine] (H-7) and Staurosporine. We show that these inhibitors can abrogate the inductive effect of TPA or the combination of TPA plus n-butyrate. The inhibitors have no effect on induction by calcium ionophores or by viral superinfection. In this context the effect of verapamil (a specific calcium channel blocker) and of several calmodulin antagonists was investigated. No inhibitory effect of these agents could be demonstrated on any of the induction systems examined. These observations strengthen the idea that in some instances cellular PKC plays a role in the expression of viral antigens; however, alternative regulatory mechanisms cannot be excluded.
authors.affiliation: Dipartimento di Medicina Sperimentale, Universitá degli Studi di Roma La Sapienza, Italy.
authors.forename: J
authors.initials: J
authors.lastname: Lazdins
authors.forename: C
authors.initials: C
authors.lastname: Zompetta
authors.forename: S
authors.initials: S
authors.lastname: Grimaldi
authors.forename: G
authors.initials: G
authors.lastname: Barile
authors.forename: M
authors.initials: M
authors.lastname: Venanzoni
authors.forename: L
authors.initials: L
authors.lastname: Frati
authors.forename: A
authors.initials: A
authors.lastname: Faggioni
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000956:Antigens, Viral / Q000096:biosynthesis*; D002051:Burkitt Lymphoma / Q000276:immunology* / Q000473:pathology; D002147:Calmodulin / Q000037:antagonists & inhibitors; D005786:Gene Expression Regulation / Q000187:drug effects; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000276:immunology; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000502:physiology; D013449:Sulfonamides / Q000494:pharmacology; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000276:immunology; D014700:Verapamil / Q000494:pharmacology
chemical_list: D000951:Antigens, Neoplasm; D000956:Antigens, Viral; D002147:Calmodulin; C033305:Epstein-Barr virus early antigen; D007546:Isoquinolines; D010879:Piperazines; D013449:Sulfonamides; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; C043204:N-(2-guanidinoethyl)-5-isoquinolinesulfonamide; D014700:Verapamil; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate