Tissue distribution of a menthyl-conjugated oligodeoxyribonucleotide antisense to PAI-1 mRNA

• Autorzy: Szemraj J. , Al-Nedawi K.N.I. , Chabielska E. , Buczko W. , Pawlowska Z.
• Języki publikacji: EN

Abstrakty

EN

The inhibitory effect of numerous analogues of PO-16, an hexadecadeoxyribonucleotide antisense to sequences -22 to -17 of PAI-1 mRNA coding for a fragment of the signal peptide, on the expression of PAI-1 in endothelial cells, and physiological consequences of the subsequently reduced PAI-1 activity tested in vitro and in vivo, were described in our previous studies. Of particular interest was PO-16 5'-O-conjugated with menthyl phosphorothioate (MPO-16R). In this work, tissue localisation of MPO-16R labelled with [35S] phosphorothioate at the 3'-end, was determined. [35S]MPO-16R and control [35S]MPO-16R-SENSE oligonucleotides were administered intravenously into 22 rats and organ distribution of the labelled bioconjugates was assessed after 24 and 48 h. For this purpose, tissue sections were subjected to autoradiography, and quantitated by liquid scintillation after solubilisation. Overall clearance of radioactivity was already seen after 24 h, with the radioactivity recovered mainly in the kidney and liver. A smaller fraction of radioactivity was also retained in the spleen and heart. The kidney concentration of the labelled probe was higher than that of liver by 50%. The distribution of PAI-1 mRNA in untreated rat kidney, liver, spleen and heart established by two independent techniques: Ribonuclease Protection Assay and Real-Time PCR, shows the same pattern as that observed for [35S]MPO-16R antisense.

Słowa kluczowe

EN

fibrinolysis regulation; antisense oligonucleotide; plasminogen activator inhibitor type 1; mRNA; menthyl-conjugated oligodeoxyribonucleotide antisense; tissue distribution; tissue plasminogen activator

• Wydawca: -
• Czasopismo: Acta Biochimica Polonica
• Rocznik: 2005
• Tom: 52
• Numer: 4
• Opis fizyczny: p.849-855,fig.,ref.

Twórcy

autor

Szemraj J.

• Medical University in Lodz, Lodz, Poland

autor

Al-Nedawi K.N.I.

autor

Chabielska E.

autor

Buczko W.

autor

Pawlowska Z.

Bibliografia

• Agrawal S, Mayrand SH, Zamecnik PC, Pederson T (1990) Site-specific excision from RNA by RNase H and mixed-phosphate-backbone oligodeoxynucleotides. Proc Natl Acad Sci USA 87: 1401–1415.
• Bajou K, Noel A, Gerard RD, Masson V, Brunner N, Holst- Hansen C, Skobe M, Fusenig NE, Carmeliet P, Collen D, Foidart JM (1998) Absence of host plasminogen activator inhibitor 1 prevents cancer invasion and vascularization. Nat Med 8: 923–928.
• Bijsterbosch MK, Manoharan M, Dorland R, Van Veghel R, Biessen EAL, Van Berkel TJC (2002) bis-Cholesterylconjugated phosphorothioate oligodeoxynucleotides are highly selectively taken up by the liver. J Pharmacol Exp Ther 302: 619–626.
• Carome MA, Kang Y-H, Bohen EM, Nicholson DE, Carr FE, Kiandoli LC, Brummel SE, Yuan CM (1997) Distribution of the cellular uptake of phosphorothioate oligodeoxynucleotides in the rat kidney in vivo. Nephron 75: 82–87.
• Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol- chloroform extraction. Anal Biochem 162: 156–159.
• Cierniewski CS, Babinska A, Swiatkowska M, Wilczynska M, Okruszek A, Stec WJ (1995) Inhibition by modified oligodeoxynucleotides of the expression of type-1 plasminogen activator inhibitor in human endothelial cells. Eur J Biochem 227: 494–509.
• Dolnick BJ (1990) Antisense agents in pharmacology. Biochem Pharmacol 40: 671–675.
• Eitzman DT, Fay WP, Lawrence DA, Francis-Chmura AM, Shore JD, Olson ST, Ginsburg D (1995) Peptide-mediated inactivation of recombinant and platelet plasminogen activator inhibitor-1 in vitro. J Clin Invest 95: 2416–2420.
• Friederich PW, Levi M, Biemond BJ, Charlton P, Templeton D, van Zonneveld AJ, Bevan P, Pannekoek H, ten Cate JW (1997) Novel low-molecular-weight inhibitor of PAI-1 (XR5118) promotes endogenous fibrinolysis and reduces postthrombolysis thrombus growth in rabbits. Circulation 96: 916–921.
• Geary RS, Watanabe TA, Truong L, Freier S, Lesnik EA, Sioufi NB, Sasmor H, Manoharan M, Levin AA (2001) Pharmacokinetic properties of 2’-O-(2-methoxyethyl)-modified oligonucleotide analogs in rats. J Pharmacol Exp Ther 296: 890–897.
• Goodarzi G, Watabe M, Watabe K (1992) Organ distribution and stability of phosphorothioated oligodeoxyribonucleotides in mice. Biopharm Drug Dispos 13: 221–227.
• Keeton M, Eguchi Y, Sawdey M, Ahn C, Loskutoff DJ (1993) Cellular localization of type 1 plasminogen activator inhibitor messenger RNA and protein in murine renal tissue. Am J Pathol 142: 59–70.
• Kobylanska A, Pluskota E, Swiątkowska M, Wojcik M, Cierniewska-Cieslak A, Krakowiak A, Boczkowska M, Pawlowska Z, Okruszek A, Koziolkiewicz M, Cierniewski C, Stec WJ (1999) Inhibition of plasminogen activator inhibitor release in endothelial cell cultures byantisense oligodeoxyribonucleotides with a 5’-end lipophilic modification. Acta Biochim Polon 46: 679–691.
• Konkle BA, Schuster SJ, Kelly MD, Harjes K, Hassett DE, Bohrer M, Tavassoli M (1992) Plasminogen activator inhibitor-1 messenger RNA expression is induced in rat hepatocytes in vivo by dexamethasone. Blood 79: 2636–2642.
• Levi M, Biemond BJ, van Zonneveld AJ, ten Cate JW, Pannekoek H (1992) Inhibition of plasminogen activator inhibitor-1 activity results in promotion of endogenous thrombolysis and inhibition of thrombus extension in models of experimental thrombosis. Circulation 85: 305–312.
• Manoharan M (2002) Oligonucleotide conjugates as potential antisense drugs with improved uptake, biodistribution, targeted delivery, and mechanism of action. Antisense Nucleic Acid Drug Dev 12: 103–128.
• Maszewska M, Kobylanska A, Gendaszewska-Darmach E, Koziolkiewicz M (2002) Bromodeoxyuridine-labelled oligonucleotides as tools for oligonucleotide uptake studies. Antisense Nucleic Acid Drug Dev 12: 379–391.
• Melton DA, Krieg PA, Rebagliati MR, Maniatis T, Zinn K, Green MR (1984) Efficient in vitro synthesis of biologically active RNA and RNA hybridization probes from plasmid containing a bacteriophage Sp6 promoter. Nucleic Acids Res 12: 7035–7056.
• Nargolwalla C, McCabe D, Fritz IB (1990) Modulation of levels of messenger RNA for tissue-type plasminogen activator in rat Sertoli cells, and levels of messenger RNA for plasminogen activator inhibitor in testis peritubular cells. Mol Cell Endocrinol 70: 73–80.
• Oikawa T, Freeman M, Lo W, Vaughan DE, Fogo A (1997) Modulation of plasminogen activator inhibitor-1 in vivo: a new mechanism for the anti-fibrotic effect of renin-angiotensin inhibition. Kidney Int 51: 164–172.
• Pawlowska Z, Pluskota E, Chabielska E, Buczko W, Okruszek A, Stec WJ, Cierniewski CS (1998) Phosphorothioate oligodeoxyribonucleotides antisense to PAI-1 mRNA increase fibrinolysis and modify experimental thrombosis in rats. Thromb Haemost 79: 348–353.
• Quax PH, van den Hoogen CM, Verheijen JH, Padro T, Zeheb R, Gelehrter TD, van Berkel TJ, Kuiper J, Emeis JJ (1990) Endotoxin induction of plasminogen activator and plasminogen activator inhibitor type 1 mRNA in rat tissues in vivo. J Biol Chem 265: 15560–15563.
• Rifai A, Brysch W, Fadden K, Clark J, Schlingensiepen KH (1996) Clearance kinetics, biodistribution, and organ saturability of phosphorothioate oligodeoxynucleotides in mice. Am J Pathol 149: 717–725.
• Sawa H, Sobel BE, Fujii S (1994) Inhibition of type-1 plasminogen activator inhibitor production by antisense oligonucleotides in human vascular endothelial and smooth muscle cells. J Biol Chem 269: 14149–14152.
• Srivastava RA, Schonfeld G (1994) Quantification of absolute amounts of cellular messenger RNA by RNA-excess solution hybridization. Methods Mol Biol 31: 273–279.
• Szklarczyk A, Kaczmarek L (1997) Pharmacokinetics of antisense analogues in the central nervous system. Neurochem Int 31: 413–423.
• van Meijer M, Pannekoek H (1995) Structure of plasminogen activator inhibitor 1 (PAI-1) and its function in fibrinolysis: an update. Fibrinolysis 9: 261–276.
• Winer J, Jung CK, Shackel I, Williams PM (1999) Development and validation of real-time quantitative reverse transcriptase-polymerase chain reaction for monitoring gene expression in cardiac myocytes in vitro. Anal Biochem 270: 41–49.