Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs

Shinji Mima; Hironori Ushijima; Hyun Jung Hwang; Shinji Tsutsumi; Masaki Makise; Yoshihiro Yamaguchi; Tomofusa Tsuchiya; Hiroshi Mizushima; Tohru Mizushima

doi:10.1016/j.febslet.2007.03.001

Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs

Shinji Mima, Hironori Ushijima, Hyun Jung Hwang, Shinji Tsutsumi, Masaki Makise, Yoshihiro Yamaguchi, Tomofusa Tsuchiya, Hiroshi Mizushima, Tohru Mizushima

Research output: Contribution to journal › Article › peer-review

20 Citations (Scopus)

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.

Original language	English
Pages (from-to)	1457-1463
Number of pages	7
Journal	FEBS Letters
Volume	581
Issue number	7
DOIs	https://doi.org/10.1016/j.febslet.2007.03.001
Publication status	Published - 2007 Apr 3
Externally published	Yes

Keywords

Non-steroidal anti-inflammatory drugs
TPO1
Tetracycline transporter-like protein

ASJC Scopus subject areas

Biophysics
Structural Biology
Biochemistry
Molecular Biology
Genetics
Cell Biology

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10.1016/j.febslet.2007.03.001

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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.",

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T1 - Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs

AU - Mima, Shinji

AU - Ushijima, Hironori

AU - Hwang, Hyun Jung

AU - Tsutsumi, Shinji

AU - Makise, Masaki

AU - Yamaguchi, Yoshihiro

AU - Tsuchiya, Tomofusa

AU - Mizushima, Hiroshi

AU - Mizushima, Tohru

PY - 2007/4/3

Y1 - 2007/4/3

N2 - 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.

AB - 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.

KW - Non-steroidal anti-inflammatory drugs

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KW - Tetracycline transporter-like protein

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Identification of the TPO1 gene in yeast, and its human orthologue TETRAN, which cause resistance to NSAIDs

Abstract

Keywords

ASJC Scopus subject areas

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