| Targeted delivery of a triplex-forming oligonucleotide to hepatic stellate cells. | |
| | |
MedLine Citation:
|
PMID: 15766277 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
|
Liver fibrosis is characterized by abnormal accumulation of extracellular matrix (ECM), namely, fibrillar collagens in the hepatic stellate cells (HSCs). Earlier, we developed an antigene approach, using a type alpha1(I) collagen gene promoter specific triplex-forming oligonucleotide (TFO) to inhibit collagen gene expression. In this paper, to enhance overall delivery of TFOs to the liver and more specifically to HSCs, we synthesized mannose 6-phosphate-bovine serum albumin (M6P-BSA) by phosphorylating p-nitrophenyl-alpha-d-mannopyranoside, reducing its nitro group, and reacting it with thiophosgene to produce p-isothiocyanatophenyl-6-phospho-alpha-d-mannopyranoside (itcM6P) for conjugation with BSA. (33)P-TFO was conjugated with M6P-BSA via a disulfide bond, and the stability of the (M6P)(20)-BSA-TFO conjugate was determined. Following tail vein injection into rats, (M6P)(20)-BSA-(33)P-TFO rapidly cleared from the circulation and accumulated mainly in the liver. Almost 66% of the injected (M6P)(20)-BSA-(33)P-TFO accumulated in the liver at 30 min postinjection, which was significantly higher than that deposited after injection of (33)P-TFO. A large proportion of the injected (M6P)(20)-BSA-(33)P-TFO was taken up by the HSCs as evidenced by determination of radioactivity in the digested liver cells upon liver perfusion and separation on a Nycodenz gradient. Therefore, this TFO conjugate may be used for the treatment of liver fibrosis. |
| | |
Authors:
|
Zhaoyang Ye; Kun Cheng; Ramareddy V Guntaka; Ram I Mahato |
Related Documents
:
|
8103107 - The effect of therapeutic doses of paracetamol on liver function in the rat perfused li... 6109737 - Clearance of immunoreactive somatostatin by perfused rat liver. 842667 - Function of the thin ascending limb of henle of rats and hamsters perfused in vitro. 3048767 - Triacylglycerol output by the isolated perfused liver of endotoxin-treated rats. 19781617 - Anti-spasmodic effects of zizyphus lotus (l.) desf. extracts on isolated rat duodenum. 8456987 - In vivo cerebrovascular reactivity in wistar and fischer 344 rat strains during aging. |
Publication Detail:
|
Type: In Vitro; Journal Article; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
|
Title: Biochemistry Volume: 44 ISSN: 0006-2960 ISO Abbreviation: Biochemistry Publication Date: 2005 Mar |
Date Detail:
|
Created Date: 2005-03-15 Completed Date: 2005-05-25 Revised Date: 2007-11-14 |
Medline Journal Info:
|
Nlm Unique ID: 0370623 Medline TA: Biochemistry Country: United States |
Other Details:
|
Languages: eng Pagination: 4466-76 Citation Subset: IM |
Affiliation:
|
Department of Pharmaceutical, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
|
Animals DNA / administration & dosage*, chemical synthesis, metabolism Disulfides / chemistry Drug Carriers / administration & dosage, chemical synthesis, metabolism Gene Targeting* / methods Liver / cytology*, metabolism* Male Mannosephosphates / administration & dosage, chemical synthesis Nucleic Acid Conformation* / drug effects Oligodeoxyribonucleotides / administration & dosage*, chemical synthesis, metabolism Perfusion Rats Rats, Sprague-Dawley Serum Albumin, Bovine / administration & dosage, chemical synthesis Succinimides / administration & dosage, chemical synthesis Thionucleotides / administration & dosage, chemical synthesis, metabolism |
| Grant Support | |
ID/Acronym/Agency:
|
47379//PHS HHS; R01 DK064633/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
|
0/Disulfides; 0/Drug Carriers; 0/Mannosephosphates; 0/Oligodeoxyribonucleotides; 0/Serum Albumin, Bovine; 0/Succinimides; 0/Thionucleotides; 0/triplex DNA; 3672-15-9/mannose-6-phosphate; 68181-17-9/N-succinimidyl 3-(2-pyridyldithio)propionate; 9007-49-2/DNA |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
Previous Document: Trans fatty acid derived phospholipids show increased membrane cholesterol and reduced receptor acti...
Next Document: The CFTR associated protein CAP70 interacts with the apical Cl-/HCO3- exchanger DRA in rabbit small ...