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Titolo:
omega-6 polyunsaturated fatty acid-stimulated cellular internalization of phosphorothioate oligodeoxynucleotides - Evidence for protein kinase C-zetadependency
Autore:
Khaled, Z; Ho, YY; Benimetskaya, L; Deckelbaum, RJ; Stein, CA;
Indirizzi:
Columbia Univ Coll Phys & Surg, Dept Med, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Pharmacol, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Dept Pediat, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA Columbia Univ Coll Phys & Surg, Inst Human Nutr, New York, NY 10032 USA Columbia Univ Coll Phys & Surg New York NY USA 10032 w York, NY 10032 USA
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 3, volume: 58, anno: 1999,
pagine: 411 - 423
SICI:
0006-2952(19990801)58:3<411:OPFACI>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHOSPHATIDYLINOSITOL 3-KINASE; GROWTH-FACTOR; ANTISENSE OLIGODEOXYNUCLEOTIDES; RECEPTOR TRAFFICKING; BINDING PROTEIN; HL-60 CELLS; 3T3 CELLS; ACTIVATION; ENDOCYTOSIS; WORTMANNIN;
Keywords:
phosphorothioate oligodeoxynucleotide; internalization; PKC-zeta; polyunsaturated fatty acid;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
43
Recensione:
Indirizzi per estratti:
Indirizzo: Stein, CA Columbia Univ Coll Phys & Surg, Dept Med, 630 W 168th St, New York, NY 10032 USA Columbia Univ Coll Phys & Surg 630 W 168th St New York NY USA 10032
Citazione:
Z. Khaled et al., "omega-6 polyunsaturated fatty acid-stimulated cellular internalization of phosphorothioate oligodeoxynucleotides - Evidence for protein kinase C-zetadependency", BIOCH PHARM, 58(3), 1999, pp. 411-423

Abstract

The rate of cellular internalization of phosphorothioate oligodeoxynucleotides is determined predominantly by adsorptive plus fluid-phase endocytosis. Internalization of a 5'-fluoresceinated phosphorothioate 15mer homopolymer of thymidine (FSdT15) in K562 cells in medium containing lipid-depleted albumin was reduced consistently versus nondepleted albumin. Treatment of K562 and several other cell lines with omega-6 polyunsaturated fatty acids (omega-6 PUFAs; e.g. arachidonic and linoleic acids) but not saturated fatty acids dramatically increased FSdT15 internalization in a concentration-dependent manner and over a wide albumin concentration range. The rate of efflux of FSdT15 from K562 cells was not affected by the omega-6 PUFA, implying that an increase of cellular fluorescence was due to an increase in the in-rate. These data were consistent with the observation that the binding of FSdT15 to the cell surface was also increased in the presence of omega-6 PUFAs. omega-6 PUFAs are stimulators of protein kinase C (PKC) activity. Inhibition of PKC activity in K562 cells by Go6976, an inhibitor of the classical PKC isoforms, did not block the linoleic acid-induced stimulation of FSdT15 internalization. On the other hand, treatment of cells with Ro318220, which has considerably less isoform specificity, almost totally blocked the effect of linoleic acid on FSdT15 internalization, implying the involvement of a nonclassical PKC isoform in the process. Finally, since the only PKC isoform expressed in K562 cells that also is activated by omega-PUFAs is PKC-xi, we obtained NIH 3T3 cells expressing a doxycycline-repressible dominant negative PKC-xi mutant. Expression of the mutant blocked the stimulation of FSdT15 internalization by linoleic acid. Stimulated internalization alsowas blocked by wortmannin and LY 294002, which are relatively specific inhibitors of phosphatidylinositol 3-kinase (PI 3-K). Taken together, our datasuggest that w-6 PUFA stimulation of fluoresceinated phosphorothioate oligomers may be PKC-xi dependent, and perhaps PI-3K dependent as well. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/10/20 alle ore 03:28:28