| Lipid raft-mediated uptake of cysteine-modified thioredoxin-1: apoptosis enhancement by inhibiting the endogenous thioredoxin-1. | |
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MedLine Citation:
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PMID: 17627472 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Thioredoxin-1 (TRX) plays important roles in cellular signaling by controlling the redox state of cysteine residues in target proteins. TRX is released in response to oxidative stress and shows various biologic functions from the extracellular environment. However, the mechanism by which extracellular TRX transduces the signal into the cells remains unclear. Here we report that the cysteine modification at the active site of TRX promotes the internalization of TRX into the cells. TRX-C35S, in which the cysteine at residue 35 of the active site was replaced with serine, was internalized more effectively than wild-type TRX in human T-cell leukemia virus-transformed T cells. TRX-C35S bound rapidly to the cell surface and was internalized into the cells dependent on lipid rafts in the plasma membrane. This process was inhibited by wild-type TRX, reducing reagents such as dithiothreitol, and methyl-beta-cyclodextrin, which disrupts lipid rafts. Moreover, the internalized TRX-C35S binds to endogenous TRX, resulting in the generation of intracellular reactive oxygen species (ROS) and enhanced cis-diamine-dichloroplatinum (II) (CDDP)-induced apoptosis via a ROS-mediated pathway involving apoptosis signal-regulating kinase-1 (ASK-1) activation. These findings suggest that the cysteine at the active site of TRX plays a key role in the internalization and signal transduction of extracellular TRX into the cells. |
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Authors:
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Norihiko Kondo; Yasuyuki Ishii; Yong-Won Kwon; Masaki Tanito; Junko Sakakura-Nishiyama; Michika Mochizuki; Michiyuki Maeda; Shigo Suzuki; Masami Kojima; Yong-Chul Kim; Aoi Son; Hajime Nakamura; Junji Yodoi |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Antioxidants & redox signaling Volume: 9 ISSN: 1523-0864 ISO Abbreviation: Antioxid. Redox Signal. Publication Date: 2007 Sep |
Date Detail:
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Created Date: 2007-08-06 Completed Date: 2007-10-04 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 100888899 Medline TA: Antioxid Redox Signal Country: United States |
Other Details:
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Languages: eng Pagination: 1439-48 Citation Subset: IM |
Affiliation:
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Department of Biological Responses, Institute for Virus Research, Kyoto University, and Thioredoxin Project, Translational Research Center Kyoto University Hospital, Kyoto, Japan. nkondoh-ivr@umin.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Amino Acid Substitution Apoptosis Cysteine Humans Jurkat Cells Membrane Microdomains / physiology* Models, Biological Recombinant Proteins / metabolism Thioredoxins / antagonists & inhibitors, genetics, metabolism* |
| Chemical | |
Reg. No./Substance:
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0/Recombinant Proteins; 52-90-4/Cysteine; 52500-60-4/Thioredoxins |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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