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rdf:type |
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lifeskim:mentions |
umls-concept:C0086418,
umls-concept:C0127400,
umls-concept:C0178499,
umls-concept:C0225369,
umls-concept:C0965144,
umls-concept:C1100939,
umls-concept:C1160185,
umls-concept:C1506764,
umls-concept:C1514562,
umls-concept:C1527178,
umls-concept:C1566354,
umls-concept:C1723137,
umls-concept:C1880389,
umls-concept:C1883204,
umls-concept:C1883221,
umls-concept:C1957815
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pubmed:issue |
4
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pubmed:dateCreated |
2007-1-16
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pubmed:abstractText |
This study was performed to investigate the transduction of a full-length superoxide dismutase (SOD) protein fused to transactivator of transcription (Tat) into human chondrocytes, and to determine the regulatory function of transduced Tat-SOD in the inflammatory cytokine induced catabolic pathway. The pTat-SOD expression vector was constructed to express the basic domain of HIV-1 Tat as a fusion protein with Cu, Zn-SOD. We also purified histidine-tagged SOD without an HIV-1 Tat and Tat-GFP as control proteins. Cartilage samples were obtained from patients with osteoarthritis (OA) and chondrocytes were cultured in both a monolayer and an explant. For the transduction of fusion proteins, cells/explants were treated with a variety of concentrations of fusion proteins. The transduced protein was detected by fluorescein labeling, western blotting and SOD activity assay. Effects of transduced Tat-SOD on the regulation of IL-1 induced nitric oxide (NO) production and inducible nitric oxide synthase (iNOS) mRNA expression was assessed by the Griess reaction and reverse transcriptase PCR, respectively. Tat-SOD was successfully delivered into both the monolayer and explant cultured chondrocytes, whereas the control SOD was not. The intracellular transduction of Tat-SOD into cultured chondrocytes was detected after 1 hours, and the amount of transduced protein did not change significantly after further incubation. SOD enzyme activity increased in a dose-dependent manner. NO production and iNOS mRNA expression, in response to IL-1 stimulation, was significantly down-regulated by pretreatment with Tat-SOD fusion proteins. This study shows that protein delivery employing the Tat-protein transduction domain is feasible as a therapeutic modality to regulate catabolic processes in cartilage. Construction of additional Tat-fusion proteins that can regulate cartilage metabolism favorably and application of this technology in in vivo models of arthritis are the subjects of future studies.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-10867027,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-11014341,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-11090949,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-11094160,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-11728823,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-11961273,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-12018858,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-12193729,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-12475933,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-12577312,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-14697220,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-14770178,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15026809,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15031670,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15223067,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15331219,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15334484,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15369775,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15601778,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-15899039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-16255039,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-2172697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-5389100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-8144628,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-9008163,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-9032389,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-9182910,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-9188504,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16792821-9292805
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:issn |
1478-6362
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pubmed:author |
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pubmed:issnType |
Electronic
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pubmed:volume |
8
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
R96
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:16792821-Cells, Cultured,
pubmed-meshheading:16792821-Chondrocytes,
pubmed-meshheading:16792821-Feasibility Studies,
pubmed-meshheading:16792821-Gene Fusion,
pubmed-meshheading:16792821-Gene Products, tat,
pubmed-meshheading:16792821-Humans,
pubmed-meshheading:16792821-Interleukin-1,
pubmed-meshheading:16792821-Nitric Oxide,
pubmed-meshheading:16792821-Nitric Oxide Synthase Type II,
pubmed-meshheading:16792821-Osteoarthritis,
pubmed-meshheading:16792821-Protein Structure, Tertiary,
pubmed-meshheading:16792821-RNA, Messenger,
pubmed-meshheading:16792821-Recombinant Fusion Proteins,
pubmed-meshheading:16792821-Superoxide Dismutase,
pubmed-meshheading:16792821-Transduction, Genetic,
pubmed-meshheading:16792821-Up-Regulation
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pubmed:year |
2006
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pubmed:articleTitle |
Transduction of Cu, Zn-superoxide dismutase mediated by an HIV-1 Tat protein basic domain into human chondrocytes.
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pubmed:affiliation |
Department of Internal Medicine, Hallym University Sacred Heart Hospital, 896, Pyongchondong, Dongan-gu, Anyang, Kyunggi-do, 431-070, Korea. kimha@hallym.ac.kr
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pubmed:publicationType |
Journal Article,
In Vitro,
Research Support, Non-U.S. Gov't
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