Mechanism of oligonucleotide uptake by cells: involvement of specific receptors?

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 86 ·No. 17 ·1989-09-00 ·Pages 6454-8

Yakubov LA, Deeva EA, Zarytova VF, Ivanova EM, Ryte AS, Yurchenko LV, Vlassov VV

Abstract

We have investigated the interaction of oligonucleotides and their alkylating derivatives with mammalian cells. In experiments with L929 mouse fibroblast and Krebs 2 ascites carcinoma cells, it was found that cellular uptake of oligodeoxynucleotide derivatives is achieved by an endocytosis mechanism. Uptake is considerably more efficient at low oligomer concentration (less than 1 microM), because at this concentration a significant percentage of the total oligomer pool is absorbed on the cell surface and internalized by a more efficient absorptive endocytosis process. Two modified proteins were detected in mouse fibroblasts that were treated with the alkylating oligonucleotide derivatives. The binding of the oligomers to the proteins is inhibited by other oligodeoxynucleotides, single- and double-stranded DNA, and RNA. The polyanions heparin and chondroitin sulfates A and B do not inhibit binding. These observations suggest the involvement of specific receptor proteins in binding of oligomers to mammalian cells.

MeSH Terms

Animals Biological Transport Carbon Radioisotopes Carcinoma, Krebs 2/metabolism Electrophoresis, Polyacrylamide Gel Kinetics L Cells/metabolism Mice Molecular Weight Oligodeoxyribonucleotides/metabolism Receptors, Cell Surface/isolation & purification,metabolism Sucrose/metabolism

Chemicals

Carbon Radioisotopes Oligodeoxyribonucleotides Receptors, Cell Surface Sucrose

Authors & Affiliations

7 authors, click to expand affiliations / ORCID

Yakubov L A

Institute of Bioorganic Chemistry, Siberian Division of the Academy of Sciences of U.S.S.R., Novosibirsk.

Deeva E A

Zarytova V F

Ivanova E M

Ryte A S

Yurchenko L V

Vlassov V V

References (18)

18 references, click to expand

Cleavage of structural proteins during the assembly of the head of bacteriophage T4.
Nature. 1970 Aug 15;227(5259):680-5 PMID: 5432063
Characterization of oligonucleotide transport into living cells.
Proc Natl Acad Sci U S A. 1989 May;86(10):3474-8 PMID: 2726730
Inhibition of Rous sarcoma virus replication and cell transformation by a specific oligodeoxynucleotide.
Proc Natl Acad Sci U S A. 1978 Jan;75(1):280-4 PMID: 75545
Harvesting the products of cell growth.
Methods Enzymol. 1979;58:221-9 PMID: 423763
Endocytosis: relation to capping and cell locomotion.
Science. 1984 May 18;224(4650):681-6 PMID: 6719108
[Suppression of immunoglobulin synthesis in myeloma MORS 21 cells by an alkylating oligonucleotide derivative complementary to the mRNA coding for light-chain immunoglobulin].
Dokl Akad Nauk SSSR. 1984;276(5):1263-5 PMID: 6434276
Quantification of endocytosis-derived membrane traffic.
Biochim Biophys Acta. 1985 Sep 9;822(2):243-66 PMID: 2992594
Complementary-addressed (sequence-specific) modification of nucleic acids.
Prog Nucleic Acid Res Mol Biol. 1985;32:291-320 PMID: 2418466
Evidence that pinocytosis in lymphoid cells has a low capacity.
J Cell Biol. 1986 Apr;102(4):1312-9 PMID: 3485637
Inhibition of replication and expression of human T-cell lymphotropic virus type III in cultured cells by exogenous synthetic oligonucleotides complementary to viral RNA.
Proc Natl Acad Sci U S A. 1986 Jun;83(12):4143-6 PMID: 3012555
Nucleotide and oligonucleotide derivatives as enzyme and nucleic acid targeted irreversible inhibitors. Chemical aspects.
Adv Enzyme Regul. 1985;24:277-99 PMID: 3915185
Nucleotide and oligonucleotide derivatives as enzyme and nucleic acid targeted irreversible inhibitors. Biochemical aspects.
Adv Enzyme Regul. 1985;24:301-20 PMID: 3835822
Human promyelocytic leukemia HL-60 cell proliferation and c-myc protein expression are inhibited by an antisense pentadecadeoxynucleotide targeted against c-myc mRNA.
Proc Natl Acad Sci U S A. 1988 Feb;85(4):1028-32 PMID: 3277186
Specific inhibition of c-myc protein biosynthesis using an antisense synthetic deoxy-oligonucleotide in human T lymphocytes.
J Immunol. 1988 Apr 1;140(7):2431-5 PMID: 2450923
A new approach to chemotherapy based on molecular biology and nucleic acid chemistry: Matagen (masking tape for gene expression).
Anticancer Drug Des. 1987 Oct;2(2):117-28 PMID: 3329522
cis-diamminedichloroplatinum(II)-resistant sublines derived from two human ovarian tumor cell lines.
Cancer Res. 1988 Jun 15;48(12):3355-9 PMID: 2897238
[Derivatives of oligonucleotides complementary to viral RNA inhibit replication of tick-borne encephalitis virus in a cell culture].
Dokl Akad Nauk SSSR. 1988;301(5):1257-60 PMID: 3229305
The pinocytosis of 125I-labelled poly(vinylpyrrolidone), [14C]sucrose and colloidal [198Au]gold by rat yolk sac cultured in vitro.
Biochem J. 1977 Nov 15;168(2):239-44 PMID: 597271

Article Info

Journal

Proceedings of the National Academy of Sciences of the United States of America

Abbr.

Proc Natl Acad Sci U S A

ISSN

0027-8424

DOI

10.1073/pnas.86.17.6454

Published

1989-09-00

Pages

6454-8

Language

English

Region

United States

NLM ID

7505876

PMCID

PMC297862

Subset

External Links

PubMed source DOI: 10.1073/pnas.86.17.6454 PMC Full Text View journal details

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