Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs.
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.
Mima
Shinji
S
Graduate School of Medical and Pharmaceutical Sciences, Kumamoto University, Kumamoto 862-0973, Japan.
Ushijima
Hironori
H
Hwang
Hyun-Jung
HJ
Tsutsumi
Shinji
S
Makise
Masaki
M
Yamaguchi
Yoshihiro
Y
Tsuchiya
Tomofusa
T
Mizushima
Hiroshi
H
Mizushima
Tohru
T
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*
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