| DDS, 4,4'-diaminodiphenylsulfone, extends organismic lifespan. | |
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MedLine Citation:
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PMID: 20974969 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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DDS, 4,4'-diaminodiphenylsulfone, is the most common drug prescribed to treat Hansen disease patients. In addition to its antibacterial activity, DDS has been reported to be involved in other cellular processes that occur in eukaryotic cells. Because DDS treatment significantly enhances the antioxidant activity in humans, we examined its effect on lifespan extension. Here we show that DDS extends organismic lifespan using Caenorhabditis elegans as a model system. DDS treatment caused a delay in aging and decreased the levels of a mitochondrial complex. The oxygen consumption rate was also significantly lowered. Consistent with these data, paraquat treatment evoked less reactive oxygen species in DDS-treated worms, and these worms were less sensitive to paraquat. Interestingly enough, all of the molecular events caused by DDS treatment were consistently reproduced in mice treated with DDS for 3 mo and in the C2C12 muscle cell line. Structural prediction identified pyruvate kinase (PK) as a protein target of DDS. Indeed, DDS bound and inhibited PK in vitro and inhibited it in vivo, and a PK mutation conferred extended lifespan of C. elegans. Supplement of pyruvate to the media protected C2C12 cells from apoptosis caused by paraquat. Our findings establish the significance of DDS in lowering reactive oxygen species generation and extending the lifespan, which renders the rationale to examining the possible effect of DDS on human lifespan extension. |
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Authors:
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Sung Chun Cho; Moon Cheol Park; Bhumsuk Keam; Jung Min Choi; Yunje Cho; Soonsil Hyun; Sang Chul Park; Junho Lee |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-10-25 |
Journal Detail:
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Title: Proceedings of the National Academy of Sciences of the United States of America Volume: 107 ISSN: 1091-6490 ISO Abbreviation: Proc. Natl. Acad. Sci. U.S.A. Publication Date: 2010 Nov |
Date Detail:
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Created Date: 2010-11-10 Completed Date: 2010-12-30 Revised Date: 2011-07-28 |
Medline Journal Info:
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Nlm Unique ID: 7505876 Medline TA: Proc Natl Acad Sci U S A Country: United States |
Other Details:
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Languages: eng Pagination: 19326-31 Citation Subset: IM |
Affiliation:
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Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul 110-799, Korea. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Aging
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drug effects Animals Antioxidants Caenorhabditis elegans / physiology* Cell Line Dapsone / pharmacology* Longevity / drug effects* Mitochondrial Proteins / drug effects Muscle, Skeletal / cytology, drug effects Oxygen Consumption / drug effects Paraquat / pharmacology Pyruvate Kinase / antagonists & inhibitors, genetics Reactive Oxygen Species |
| Chemical | |
Reg. No./Substance:
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0/Antioxidants; 0/Mitochondrial Proteins; 0/Reactive Oxygen Species; 4685-14-7/Paraquat; 80-08-0/Dapsone; EC 2.7.1.40/Pyruvate Kinase |
| Comments/Corrections | |
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