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

21 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

Cite this

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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.",

keywords = "Non-steroidal anti-inflammatory drugs, TPO1, Tetracycline transporter-like protein",

author = "Shinji Mima and Hironori Ushijima and Hwang, \{Hyun Jung\} and Shinji Tsutsumi and Masaki Makise and Yoshihiro Yamaguchi and Tomofusa Tsuchiya and Hiroshi Mizushima and Tohru Mizushima",

year = "2007",

month = apr,

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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

KW - TPO1

KW - Tetracycline transporter-like protein

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JF - FEBS Letters

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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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