Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells.
Identifieur interne : 000E95 ( Main/Exploration ); précédent : 000E94; suivant : 000E96Clathrin-dependent endocytosis of claudin-2 by DFYSP peptide causes lysosomal damage in lung adenocarcinoma A549 cells.
Auteurs : Akira Ikari [Japon] ; Saeko Taga [Japon] ; Ryo Watanabe [Japon] ; Tomonari Sato [Japon] ; Shun Shimobaba [Japon] ; Hiroyuki Sonoki [Japon] ; Satoshi Endo [Japon] ; Toshiyuki Matsunaga [Japon] ; Hideki Sakai [Japon] ; Masahiko Yamaguchi [Japon] ; Yasuhiro Yamazaki [Japon] ; Junko Sugatani [Japon]Source :
- Biochimica et biophysica acta [ 0006-3002 ] ; 2015.
Descripteurs français
- KwdFr :
- Apoptose (), Clathrine (métabolisme), Claudine-2 (métabolisme), Endocytose (), Humains, Lignée cellulaire tumorale, Lysosomes (), Lysosomes (anatomopathologie), Lysosomes (métabolisme), Peptides (administration et posologie), Relation dose-effet des médicaments, Tumeurs du poumon (anatomopathologie), Tumeurs du poumon (métabolisme).
- MESH :
- administration et posologie : Peptides.
- anatomopathologie : Lysosomes, Tumeurs du poumon.
- métabolisme : Clathrine, Claudine-2, Lysosomes, Tumeurs du poumon.
- Apoptose, Endocytose, Humains, Lignée cellulaire tumorale, Lysosomes, Relation dose-effet des médicaments.
English descriptors
- KwdEn :
- Apoptosis (drug effects), Cell Line, Tumor, Clathrin (metabolism), Claudin-2 (metabolism), Dose-Response Relationship, Drug, Endocytosis (drug effects), Humans, Lung Neoplasms (metabolism), Lung Neoplasms (pathology), Lysosomes (drug effects), Lysosomes (metabolism), Lysosomes (pathology), Peptides (administration & dosage).
- MESH :
- chemical , administration & dosage : Peptides.
- chemical , metabolism : Clathrin, Claudin-2.
- drug effects : Apoptosis, Endocytosis, Lysosomes.
- metabolism : Lung Neoplasms, Lysosomes.
- pathology : Lung Neoplasms, Lysosomes.
- Cell Line, Tumor, Dose-Response Relationship, Drug, Humans.
Abstract
Claudins are tight junctional proteins and comprise a family of over 20 members. Abnormal expression of claudins is reported to be involved in tumor progression. Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases cell proliferation, whereas it is not expressed in normal tissues. Claudin-2-targeting molecules such as peptides and small molecules may be novel anti-cancer drugs. The short peptide with the sequence DFYSP, which mimics the second extracellular loop of claudin-2, decreased claudin-2 content in the cytoplasmic fraction of A549 cells. In contrast, it did not affect the content in the nuclear fraction. The decrease in claudin-2 content was inhibited by chloroquine (CQ), a lysosomal inhibitor, but not by MG-132, a proteasome inhibitor. In the presence of DFYSP peptide and CQ, claudin-2 was co-localized with LAMP-1, a lysosomal marker. The DFYSP peptide-induced decrease in claudin-2 content was inhibited by monodancylcadaverine (MDC), an inhibitor of clathrin-dependent endocytosis. DFYSP peptide increased lysosome content and cathepsin B release, and induced cellular injury, which were inhibited by MDC. Cellular injury induced by DFYSP peptide was inhibited by necrostatin-1, an inhibitor of necrotic cell death, but not by Z-VAD-FMK, an inhibitor of apoptotic cell death. Our data indicate that DFYSP peptide increases the accumulation of the peptide and claudin-2 into the lysosome, resulting in lysosomal damage. Claudin-2 may be a new target for lung cancer therapy.
DOI: 10.1016/j.bbamem.2015.07.003
PubMed: 26163137
Affiliations:
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last="Shimobaba">Shun Shimobaba</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Sonoki, Hiroyuki" sort="Sonoki, Hiroyuki" uniqKey="Sonoki H" first="Hiroyuki" last="Sonoki">Hiroyuki Sonoki</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Endo, Satoshi" sort="Endo, Satoshi" uniqKey="Endo S" first="Satoshi" last="Endo">Satoshi Endo</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Matsunaga, Toshiyuki" sort="Matsunaga, Toshiyuki" uniqKey="Matsunaga T" first="Toshiyuki" last="Matsunaga">Toshiyuki Matsunaga</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country 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of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author><author><name sortKey="Yamazaki, Yasuhiro" sort="Yamazaki, Yasuhiro" uniqKey="Yamazaki Y" first="Yasuhiro" last="Yamazaki">Yasuhiro Yamazaki</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmaceutical Sciences, University of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author><author><name sortKey="Sugatani, Junko" sort="Sugatani, Junko" uniqKey="Sugatani J" first="Junko" last="Sugatani">Junko Sugatani</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmaceutical Sciences, University of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author></titleStmt><publicationStmt><idno type="wicri:source">PubMed</idno><date when="2015">2015</date><idno type="RBID">pubmed:26163137</idno><idno type="pmid">26163137</idno><idno type="doi">10.1016/j.bbamem.2015.07.003</idno><idno type="wicri:Area/PubMed/Corpus">000243</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Corpus" wicri:corpus="PubMed">000243</idno><idno type="wicri:Area/PubMed/Curation">000243</idno><idno type="wicri:explorRef" wicri:stream="PubMed" wicri:step="Curation">000243</idno><idno type="wicri:Area/PubMed/Checkpoint">000248</idno><idno type="wicri:explorRef" wicri:stream="Checkpoint" wicri:step="PubMed">000248</idno><idno type="wicri:Area/Ncbi/Merge">000302</idno><idno type="wicri:Area/Ncbi/Curation">000302</idno><idno 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Electronic address: ikari@gifu-pu.ac.jp.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Taga, Saeko" sort="Taga, Saeko" uniqKey="Taga S" first="Saeko" last="Taga">Saeko Taga</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Watanabe, Ryo" sort="Watanabe, Ryo" uniqKey="Watanabe R" first="Ryo" last="Watanabe">Ryo Watanabe</name><affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama</wicri:regionArea><wicri:noRegion>University of Toyama</wicri:noRegion></affiliation></author><author><name sortKey="Sato, Tomonari" sort="Sato, Tomonari" uniqKey="Sato T" first="Tomonari" last="Sato">Tomonari Sato</name><affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama</wicri:regionArea><wicri:noRegion>University of Toyama</wicri:noRegion></affiliation></author><author><name sortKey="Shimobaba, Shun" sort="Shimobaba, Shun" uniqKey="Shimobaba S" first="Shun" last="Shimobaba">Shun Shimobaba</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Sonoki, Hiroyuki" sort="Sonoki, Hiroyuki" uniqKey="Sonoki H" first="Hiroyuki" last="Sonoki">Hiroyuki Sonoki</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Endo, Satoshi" sort="Endo, Satoshi" uniqKey="Endo S" first="Satoshi" last="Endo">Satoshi Endo</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Matsunaga, Toshiyuki" sort="Matsunaga, Toshiyuki" uniqKey="Matsunaga T" first="Toshiyuki" last="Matsunaga">Toshiyuki Matsunaga</name><affiliation wicri:level="1"><nlm:affiliation>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>The Laboratory of Biochemistry, Department of Biopharmaceutical Sciences, Gifu Pharmaceutical University</wicri:regionArea><wicri:noRegion>Gifu Pharmaceutical University</wicri:noRegion></affiliation></author><author><name sortKey="Sakai, Hideki" sort="Sakai, Hideki" uniqKey="Sakai H" first="Hideki" last="Sakai">Hideki Sakai</name><affiliation wicri:level="1"><nlm:affiliation>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama</wicri:regionArea><wicri:noRegion>University of Toyama</wicri:noRegion></affiliation></author><author><name sortKey="Yamaguchi, Masahiko" sort="Yamaguchi, Masahiko" uniqKey="Yamaguchi M" first="Masahiko" last="Yamaguchi">Masahiko Yamaguchi</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmaceutical Sciences, University of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author><author><name sortKey="Yamazaki, Yasuhiro" sort="Yamazaki, Yasuhiro" uniqKey="Yamazaki Y" first="Yasuhiro" last="Yamazaki">Yasuhiro Yamazaki</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmaceutical Sciences, University of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author><author><name sortKey="Sugatani, Junko" sort="Sugatani, Junko" uniqKey="Sugatani J" first="Junko" last="Sugatani">Junko Sugatani</name><affiliation wicri:level="1"><nlm:affiliation>School of Pharmaceutical Sciences, University of Shizuoka, Japan.</nlm:affiliation><country xml:lang="fr">Japon</country><wicri:regionArea>School of Pharmaceutical Sciences, University of Shizuoka</wicri:regionArea><wicri:noRegion>University of Shizuoka</wicri:noRegion></affiliation></author></analytic><series><title level="j">Biochimica et biophysica acta</title><idno type="ISSN">0006-3002</idno><imprint><date when="2015" type="published">2015</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Apoptosis (drug effects)</term><term>Cell Line, Tumor</term><term>Clathrin (metabolism)</term><term>Claudin-2 (metabolism)</term><term>Dose-Response Relationship, Drug</term><term>Endocytosis (drug effects)</term><term>Humans</term><term>Lung Neoplasms (metabolism)</term><term>Lung Neoplasms (pathology)</term><term>Lysosomes (drug effects)</term><term>Lysosomes (metabolism)</term><term>Lysosomes (pathology)</term><term>Peptides (administration & dosage)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Apoptose ()</term><term>Clathrine (métabolisme)</term><term>Claudine-2 (métabolisme)</term><term>Endocytose ()</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Lysosomes ()</term><term>Lysosomes (anatomopathologie)</term><term>Lysosomes (métabolisme)</term><term>Peptides (administration et posologie)</term><term>Relation dose-effet des médicaments</term><term>Tumeurs du poumon (anatomopathologie)</term><term>Tumeurs du poumon (métabolisme)</term></keywords><keywords scheme="MESH" type="chemical" qualifier="administration & dosage" xml:lang="en"><term>Peptides</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Clathrin</term><term>Claudin-2</term></keywords><keywords scheme="MESH" qualifier="administration et posologie" xml:lang="fr"><term>Peptides</term></keywords><keywords scheme="MESH" qualifier="anatomopathologie" xml:lang="fr"><term>Lysosomes</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Apoptosis</term><term>Endocytosis</term><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Lung Neoplasms</term><term>Lysosomes</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Clathrine</term><term>Claudine-2</term><term>Lysosomes</term><term>Tumeurs du poumon</term></keywords><keywords scheme="MESH" qualifier="pathology" xml:lang="en"><term>Lung Neoplasms</term><term>Lysosomes</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Cell Line, Tumor</term><term>Dose-Response Relationship, Drug</term><term>Humans</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Apoptose</term><term>Endocytose</term><term>Humains</term><term>Lignée cellulaire tumorale</term><term>Lysosomes</term><term>Relation dose-effet des médicaments</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Claudins are tight junctional proteins and comprise a family of over 20 members. Abnormal expression of claudins is reported to be involved in tumor progression. Claudin-2 is highly expressed in lung adenocarcinoma tissues and increases cell proliferation, whereas it is not expressed in normal tissues. Claudin-2-targeting molecules such as peptides and small molecules may be novel anti-cancer drugs. The short peptide with the sequence DFYSP, which mimics the second extracellular loop of claudin-2, decreased claudin-2 content in the cytoplasmic fraction of A549 cells. In contrast, it did not affect the content in the nuclear fraction. The decrease in claudin-2 content was inhibited by chloroquine (CQ), a lysosomal inhibitor, but not by MG-132, a proteasome inhibitor. In the presence of DFYSP peptide and CQ, claudin-2 was co-localized with LAMP-1, a lysosomal marker. The DFYSP peptide-induced decrease in claudin-2 content was inhibited by monodancylcadaverine (MDC), an inhibitor of clathrin-dependent endocytosis. DFYSP peptide increased lysosome content and cathepsin B release, and induced cellular injury, which were inhibited by MDC. Cellular injury induced by DFYSP peptide was inhibited by necrostatin-1, an inhibitor of necrotic cell death, but not by Z-VAD-FMK, an inhibitor of apoptotic cell death. Our data indicate that DFYSP peptide increases the accumulation of the peptide and claudin-2 into the lysosome, resulting in lysosomal damage. Claudin-2 may be a new target for lung cancer therapy.</div></front></TEI><affiliations><list><country><li>Japon</li></country></list><tree><country name="Japon"><noRegion><name sortKey="Ikari, Akira" sort="Ikari, Akira" uniqKey="Ikari A" first="Akira" last="Ikari">Akira Ikari</name></noRegion><name sortKey="Endo, Satoshi" sort="Endo, Satoshi" uniqKey="Endo S" first="Satoshi" last="Endo">Satoshi Endo</name><name sortKey="Matsunaga, Toshiyuki" sort="Matsunaga, Toshiyuki" uniqKey="Matsunaga T" first="Toshiyuki" last="Matsunaga">Toshiyuki Matsunaga</name><name sortKey="Sakai, Hideki" sort="Sakai, Hideki" uniqKey="Sakai H" first="Hideki" last="Sakai">Hideki Sakai</name><name sortKey="Sato, Tomonari" sort="Sato, Tomonari" uniqKey="Sato T" first="Tomonari" last="Sato">Tomonari Sato</name><name sortKey="Shimobaba, Shun" sort="Shimobaba, Shun" uniqKey="Shimobaba S" first="Shun" last="Shimobaba">Shun Shimobaba</name><name sortKey="Sonoki, Hiroyuki" sort="Sonoki, Hiroyuki" uniqKey="Sonoki H" first="Hiroyuki" last="Sonoki">Hiroyuki Sonoki</name><name sortKey="Sugatani, Junko" sort="Sugatani, Junko" uniqKey="Sugatani J" first="Junko" last="Sugatani">Junko Sugatani</name><name sortKey="Taga, Saeko" sort="Taga, Saeko" uniqKey="Taga S" first="Saeko" last="Taga">Saeko Taga</name><name sortKey="Watanabe, Ryo" sort="Watanabe, Ryo" uniqKey="Watanabe R" first="Ryo" last="Watanabe">Ryo Watanabe</name><name sortKey="Yamaguchi, Masahiko" sort="Yamaguchi, Masahiko" uniqKey="Yamaguchi M" first="Masahiko" last="Yamaguchi">Masahiko Yamaguchi</name><name sortKey="Yamazaki, Yasuhiro" sort="Yamazaki, Yasuhiro" uniqKey="Yamazaki Y" first="Yasuhiro" last="Yamazaki">Yasuhiro Yamazaki</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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