Abstract
Non-steroidal anti-inflammatory drugs (NSAIDs), such as indomethacin, have serious gastrointestinal side effects. Since their direct cytotoxicity was suggested to be involved in this side effect, we here tried to identify NSAID-resistant genes. We screened for Saccharomyces cerevisiae genes whose overexpression causes indomethacin resistance and identified the TPO1 gene, which encodes a major facilitator superfamily transporter. Its overexpression or deletion made yeast cells resistant or sensitive, respectively, to some NSAIDs. A BLAST search identified the possible human orthologue of Tpo1p, tetracycline transporter-like protein (TETRAN), whose overexpression in cultured human cells caused resistance to some NSAIDs, suggesting that TETRAN is an efflux pump for some NSAIDs.
MeSH terms
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Amino Acid Sequence
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Anti-Inflammatory Agents, Non-Steroidal / toxicity*
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Antiporters
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Cells, Cultured
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Computational Biology
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Drug Resistance / genetics*
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Gene Deletion
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Genetic Testing
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Humans
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Membrane Transport Proteins / chemistry
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Membrane Transport Proteins / genetics
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Membrane Transport Proteins / physiology*
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Molecular Sequence Data
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Mutation
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Organic Cation Transport Proteins
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RNA, Messenger / analysis
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RNA, Messenger / metabolism
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Saccharomyces cerevisiae / drug effects*
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Saccharomyces cerevisiae / genetics*
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Saccharomyces cerevisiae Proteins / chemistry
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Saccharomyces cerevisiae Proteins / genetics
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Saccharomyces cerevisiae Proteins / physiology*
Substances
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Anti-Inflammatory Agents, Non-Steroidal
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Antiporters
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Membrane Transport Proteins
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Organic Cation Transport Proteins
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RNA, Messenger
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Saccharomyces cerevisiae Proteins
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TETRAN protein, human
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TPO1 protein, S cerevisiae