title: Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs.
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.
authors.affiliation: Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Mima
authors.forename: Hironori
authors.initials: H
authors.lastname: Ushijima
authors.forename: Hyun-Jung
authors.initials: HJ
authors.lastname: Hwang
authors.forename: Shinji
authors.initials: S
authors.lastname: Tsutsumi
authors.forename: Masaki
authors.initials: M
authors.lastname: Makise
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Yamaguchi
authors.forename: Tomofusa
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mizushima
authors.forename: Tohru
authors.initials: T
authors.lastname: Mizushima
mesh_terms: D000595:Amino Acid Sequence; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000633:toxicity*; D017920:Antiporters; D002478:Cells, Cultured; D019295:Computational Biology; D004351:Drug Resistance / Q000235:genetics*; D017353:Gene Deletion; D005820:Genetic Testing; D006801:Humans; D026901:Membrane Transport Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D008969:Molecular Sequence Data; D009154:Mutation; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000187:drug effects* / Q000235:genetics*; D029701:Saccharomyces cerevisiae Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D017920:Antiporters; D026901:Membrane Transport Proteins; D027701:Organic Cation Transport Proteins; D012333:RNA, Messenger; D029701:Saccharomyces cerevisiae Proteins; C519998:MFSD10 protein, human; C475058:TPO1 protein, S cerevisiae