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Titolo:
ANTISENSE SUPPRESSION OF PROTEIN-KINASE-C-ALPHA AND PROTEIN-KINASE-DELTA IN VASCULAR SMOOTH-MUSCLE
Autore:
BUSUTTIL SJ; MOREHOUSE DL; YOUKEY JR; SINGER HA;
Indirizzi:
GEISINGER MED CLIN,DEPT VASC SURG DANVILLE PA 17822 GEISINGER MED CLIN,SIGFRIED & JANET WEIS CTR RES DANVILLE PA 17822
Titolo Testata:
The Journal of surgical research
fascicolo: 1, volume: 63, anno: 1996,
pagine: 137 - 142
SICI:
0022-4804(1996)63:1<137:ASOPAP>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
INHIBITION; ACTIVATION; OLIGONUCLEOTIDES; HYPERPLASIA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
26
Recensione:
Indirizzi per estratti:
Citazione:
S.J. Busuttil et al., "ANTISENSE SUPPRESSION OF PROTEIN-KINASE-C-ALPHA AND PROTEIN-KINASE-DELTA IN VASCULAR SMOOTH-MUSCLE", The Journal of surgical research, 63(1), 1996, pp. 137-142

Abstract

Understanding and being able to manipulate intracellular signaling pathways which control VSMC gene expression and proliferation will be important in efforts to control neointimal hyperplastic vascular diseases. Activation of the protein kinase C (PKC) family of enzymes is a central event in growth factor-stimulated cells. PKC activation results in the activation of downstream protein kinases including mitogen activated protein kinase (MAPK). PKC isozymes alpha (alpha) and delta (delta) predominate in cultured rat aortic VSMC and both isozymes are completely downregulated upon prolonged (16-24 hr) stimulation with the PKCactivator, phorbol 12,13 dibutyrate (PDBu). At these low levels of PKC, MAPK activation in response to PDBu is nearly abolished. To assess the role of specific PKC isozymes in regulating MAPK, isozyme-specificantisense oligodeoxynucleotides (ODNs) were used to inhibit reexpression of PKC in downregulated cells. ODNs were phosphorothioated to increase stability and contained C-5 propynyl modified pyrimidines which are reported to have increased binding affinity. ODNs were administeredin low concentration (400 nM) with a cationic liposome carrier (Lipofectin; GibcoBRL). Optical imaging of cells treated with FITC-labeled ODNs confirmed that virtually all cells took up the ODNs within 2 hr. With this technique, PKC alpha-specific antisense ODNs selectively inhibited PKC alpha recovery compared to cells treated with an equal length nonsense ODN (76 +/- 3.9, P < 0.001), with no effect on recovery of PKC delta. However, activation of MASK by PDBu was not significantly inhibited in these PKC alpha downregulated cells. This suggests that only a small amount of the total PKC alpha is required for PDBu induced activation of MAPK and/or that PKC delta can mediate the response. Manipulation of PKC isozymes using this model system should allow assessment of the roles of specific isozymes in controlling diverse downstream effecters and events related to VSMC growth and proliferation. 1996 Academic Press, Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 08/08/20 alle ore 16:55:07