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Titolo:
MULTIPLE MECHANISMS MAY CONTRIBUTE TO THE CELLULAR ANTIADHESIVE EFFECTS OF PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES
Autore:
KHALED Z; BENIMETSKAYA L; ZELTSER R; KHAN T; SHARMA HW; NARAYANAN R; STEIN CA;
Indirizzi:
COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,630 W 168 ST NEW YORK NY 10032 COLUMBIA UNIV COLL PHYS & SURG,DEPT MED NEW YORK NY 10032 HOFFMANN LA ROCHE INC,ROCHE RES CTR,DIV ONCOL NUTLEY NJ 07110
Titolo Testata:
Nucleic acids research
fascicolo: 4, volume: 24, anno: 1996,
pagine: 737 - 745
SICI:
0305-1048(1996)24:4<737:MMMCTT>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
NF-KAPPA-B; ANTISENSE OLIGONUCLEOTIDES; INHIBITION; PROTEINS; LAMININ; BINDING; FIBRONECTIN; SURAMIN; DNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
34
Recensione:
Indirizzi per estratti:
Citazione:
Z. Khaled et al., "MULTIPLE MECHANISMS MAY CONTRIBUTE TO THE CELLULAR ANTIADHESIVE EFFECTS OF PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDES", Nucleic acids research, 24(4), 1996, pp. 737-745

Abstract

Phosphorothioate oligodeoxynucleotides complementary to the p65 (Rel A) subunit of the NF-kappa B nuclear transcriptional regulatory factorhave been suggested to be sequence specific blockers of cellular adhesion. We studied the effects of Rel A antisense, Rel A sense and otherphosphorothioate oligodeoxynucleotides on cellular adhesion and foundthat blockade of adhesion was predominately non-sequence specific, Phosphorothioate oligodeoxynucleotides bind to the extracellular matrix (ECM) of NIH 3T3 cells, and to the ECM elements laminin and fibronectin. By use of a gel mobility shift assay, the association of the A subunit of laminin with a probe 12mer phosphodiester oligodeoxynucleotide could be demonstrated. This interaction was described by a single-sitebinding equation (K-d = 14 mu M). Human Rel A antisense and sense oligodeoxynucleotides, and two synthetic persulfated heparin analogs wereexcellent competitors of the binding of the probe oligodeoxynucleotide to laminin. Taken together, these data indicate that oligodeoxynucleotide binding occurred at or near the heparin-binding site. Competition for 5' P-32-SdT18 (an 18mer phosphorothioate homopolymer of thymidine) binding to fibronectin with the discrete heparin analogs, as well as with SdC(28), was also observed. Phosphorothioate oligodeoxynucleotides (Rel A antisense >> Rel A sense) inhibited the binding of laminin to bovine brain sulfatide, but not to its cell surface receptors on MCF-7 cells. By flow cytometric analysis we have also shown, in contrastto what was observed with laminin, that phosphorothioates non-specifically block the specific binding of fluoresceinated fibronectin to itscell surface receptors on phorbol-12,13-myristate acetate-treated Jurkat cells. Blockade of specific binding occurred in the oligodeoxynucleotide treated cells in the presence or absence of oligomer in the media.

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Documento generato il 27/11/20 alle ore 13:00:24