Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1
Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood d-/l -serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not...
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| Veröffentlicht in: | Scientific reports 2019-11, Vol.9 (1), p.16705-11, Article 16705 |
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| creator | Suzuki, Masataka Gonda, Yusuke Yamada, Marina Vandebroek, Arno A. Mita, Masashi Hamase, Kenji Yasui, Masato Sasabe, Jumpei |
| description | Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood
d-/l
-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum
d-/l
-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased
d-/l
-serine ratio did not associate with activity of a
d
-serine degrading enzyme,
d
-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum
d
-serine increase.
In vitro
study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of
d
-serine preferably to
l
-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum
d
-serine accumulation. |
| doi_str_mv | 10.1038/s41598-019-53302-2 |
| format | Article |
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d-/l
-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum
d-/l
-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased
d-/l
-serine ratio did not associate with activity of a
d
-serine degrading enzyme,
d
-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum
d
-serine increase.
In vitro
study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of
d
-serine preferably to
l
-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum
d
-serine accumulation.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/s41598-019-53302-2</identifier><identifier>PMID: 31723194</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/92/577 ; 692/4022/272 ; 692/53 ; Amino acid oxidase ; Amino Acid Transport System y ; Amino acids ; Animals ; Antineoplastic Agents - toxicity ; Blood ; Cisplatin ; Cisplatin - toxicity ; Creatinine ; D-Amino-acid oxidase ; D-Amino-Acid Oxidase - metabolism ; D-Serine ; Enantiomers ; Humanities and Social Sciences ; Kidney diseases ; Kidney Diseases - blood ; Kidney Diseases - chemically induced ; Kidney Diseases - pathology ; Kidney Tubules, Proximal - injuries ; Kidney Tubules, Proximal - metabolism ; Kidneys ; L-Serine ; Male ; Mice ; Mice, Inbred C57BL ; multidisciplinary ; Proximal tubules ; Renal tubules ; Science ; Science (multidisciplinary) ; Serine - blood ; Serine - urine ; Stereoisomerism ; Transcription ; Urine</subject><ispartof>Scientific reports, 2019-11, Vol.9 (1), p.16705-11, Article 16705</ispartof><rights>The Author(s) 2019</rights><rights>2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c540t-5f0669badfa61fc34c0acfd9f017181cf18656d6668418710827ba9f061e4b263</citedby><cites>FETCH-LOGICAL-c540t-5f0669badfa61fc34c0acfd9f017181cf18656d6668418710827ba9f061e4b263</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853873/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC6853873/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,41096,42165,51551,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31723194$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Suzuki, Masataka</creatorcontrib><creatorcontrib>Gonda, Yusuke</creatorcontrib><creatorcontrib>Yamada, Marina</creatorcontrib><creatorcontrib>Vandebroek, Arno A.</creatorcontrib><creatorcontrib>Mita, Masashi</creatorcontrib><creatorcontrib>Hamase, Kenji</creatorcontrib><creatorcontrib>Yasui, Masato</creatorcontrib><creatorcontrib>Sasabe, Jumpei</creatorcontrib><title>Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood
d-/l
-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum
d-/l
-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased
d-/l
-serine ratio did not associate with activity of a
d
-serine degrading enzyme,
d
-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum
d
-serine increase.
In vitro
study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of
d
-serine preferably to
l
-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum
d
-serine accumulation.</description><subject>631/92/577</subject><subject>692/4022/272</subject><subject>692/53</subject><subject>Amino acid oxidase</subject><subject>Amino Acid Transport System y</subject><subject>Amino acids</subject><subject>Animals</subject><subject>Antineoplastic Agents - toxicity</subject><subject>Blood</subject><subject>Cisplatin</subject><subject>Cisplatin - toxicity</subject><subject>Creatinine</subject><subject>D-Amino-acid oxidase</subject><subject>D-Amino-Acid Oxidase - metabolism</subject><subject>D-Serine</subject><subject>Enantiomers</subject><subject>Humanities and Social Sciences</subject><subject>Kidney diseases</subject><subject>Kidney Diseases - blood</subject><subject>Kidney Diseases - chemically induced</subject><subject>Kidney Diseases - pathology</subject><subject>Kidney Tubules, Proximal - injuries</subject><subject>Kidney Tubules, Proximal - metabolism</subject><subject>Kidneys</subject><subject>L-Serine</subject><subject>Male</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>multidisciplinary</subject><subject>Proximal tubules</subject><subject>Renal tubules</subject><subject>Science</subject><subject>Science (multidisciplinary)</subject><subject>Serine - blood</subject><subject>Serine - urine</subject><subject>Stereoisomerism</subject><subject>Transcription</subject><subject>Urine</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9UU1v3CAQRVWqJtrmD_RQIfVMwwDG-FIpitImUqQe2p4RxrB1tIYt2Kv032e2m69ewgEGvTdvPh4hH4B_Bi7NWVXQdIZx6FgjJRdMvCEngquGCSnE0Yv4mJzWesvxNKJT0L0jxxJaIaFTJ2T6Ecoy0YHVUMYUqPN-mZaNm8ecqItzKHRb8t04uQ0tIeE9Lz3ihQ5ucutAx7TLm12oNIVlLoi7aUwZdcaB4j_VbS57lfPqGbwnb6Pb1HD68K7Ir6-XPy-u2M33b9cX5zfMN4rPrIlc6653Q3QaopfKc-fj0EUOLRjwEYxu9KC1NgpMC9yItncIawiqF1quyJeD7nbppzD4kPat2W3BOcpfm91o_0fS-Nuu885q00jTShT49CBQ8p8l1Nne5qXg-NXi4hTur5MGWeLA8iXXWkJ8qgDc7l2yB5csumT_uYTZK_LxZW9PKY-eIEEeCBWhtA7lufYrsvdn3p8v</recordid><startdate>20191113</startdate><enddate>20191113</enddate><creator>Suzuki, Masataka</creator><creator>Gonda, Yusuke</creator><creator>Yamada, Marina</creator><creator>Vandebroek, Arno A.</creator><creator>Mita, Masashi</creator><creator>Hamase, Kenji</creator><creator>Yasui, Masato</creator><creator>Sasabe, Jumpei</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>5PM</scope></search><sort><creationdate>20191113</creationdate><title>Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1</title><author>Suzuki, Masataka ; Gonda, Yusuke ; Yamada, Marina ; Vandebroek, Arno A. ; Mita, Masashi ; Hamase, Kenji ; Yasui, Masato ; Sasabe, Jumpei</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c540t-5f0669badfa61fc34c0acfd9f017181cf18656d6668418710827ba9f061e4b263</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2019</creationdate><topic>631/92/577</topic><topic>692/4022/272</topic><topic>692/53</topic><topic>Amino acid oxidase</topic><topic>Amino Acid Transport System y</topic><topic>Amino acids</topic><topic>Animals</topic><topic>Antineoplastic Agents - toxicity</topic><topic>Blood</topic><topic>Cisplatin</topic><topic>Cisplatin - toxicity</topic><topic>Creatinine</topic><topic>D-Amino-acid oxidase</topic><topic>D-Amino-Acid Oxidase - metabolism</topic><topic>D-Serine</topic><topic>Enantiomers</topic><topic>Humanities and Social Sciences</topic><topic>Kidney diseases</topic><topic>Kidney Diseases - blood</topic><topic>Kidney Diseases - chemically induced</topic><topic>Kidney Diseases - pathology</topic><topic>Kidney Tubules, Proximal - injuries</topic><topic>Kidney Tubules, Proximal - metabolism</topic><topic>Kidneys</topic><topic>L-Serine</topic><topic>Male</topic><topic>Mice</topic><topic>Mice, Inbred C57BL</topic><topic>multidisciplinary</topic><topic>Proximal tubules</topic><topic>Renal tubules</topic><topic>Science</topic><topic>Science (multidisciplinary)</topic><topic>Serine - blood</topic><topic>Serine - urine</topic><topic>Stereoisomerism</topic><topic>Transcription</topic><topic>Urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Suzuki, Masataka</creatorcontrib><creatorcontrib>Gonda, Yusuke</creatorcontrib><creatorcontrib>Yamada, Marina</creatorcontrib><creatorcontrib>Vandebroek, Arno A.</creatorcontrib><creatorcontrib>Mita, Masashi</creatorcontrib><creatorcontrib>Hamase, Kenji</creatorcontrib><creatorcontrib>Yasui, Masato</creatorcontrib><creatorcontrib>Sasabe, Jumpei</creatorcontrib><collection>Springer Nature OA/Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Suzuki, Masataka</au><au>Gonda, Yusuke</au><au>Yamada, Marina</au><au>Vandebroek, Arno A.</au><au>Mita, Masashi</au><au>Hamase, Kenji</au><au>Yasui, Masato</au><au>Sasabe, Jumpei</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2019-11-13</date><risdate>2019</risdate><volume>9</volume><issue>1</issue><spage>16705</spage><epage>11</epage><pages>16705-11</pages><artnum>16705</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Chiral separation has revealed enantio-specific changes in blood and urinary levels of amino acids in kidney diseases. Blood
d-/l
-serine ratio has been identified to have a correlation with creatinine-based kidney function. However, the mechanism of distinctive behavior in serine enantiomers is not well understood. This study was performed to investigate the role of renal tubules in derangement of serine enantiomers using a mouse model of cisplatin-induced tubular injury. Cisplatin treatment resulted in tubular damage histologically restricted to the proximal tubules and showed a significant increase of serum
d-/l
-serine ratio with positive correlations to serum creatinine and blood urine nitrogen (BUN). The increased
d-/l
-serine ratio did not associate with activity of a
d
-serine degrading enzyme,
d
-amino acid oxidase, in the kidney. Screening transcriptions of neutral amino acid transporters revealed that Asc-1, found in renal tubules and collecting ducts, was significantly increased after cisplatin-treatment, which correlates with serum
d
-serine increase.
In vitro
study using a kidney cell line showed that Asc-1 is induced by cisplatin and mediated influx of
d
-serine preferably to
l
-serine. Collectively, these results suggest that cisplatin-induced damage of proximal tubules accompanies Asc-1 induction in tubules and collecting ducts and leads to serum
d
-serine accumulation.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>31723194</pmid><doi>10.1038/s41598-019-53302-2</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Scientific reports, 2019-11, Vol.9 (1), p.16705-11, Article 16705 |
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| language | eng |
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| source | MEDLINE; Nature Free; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Alma/SFX Local Collection; Springer Nature OA/Free Journals; Free Full-Text Journals in Chemistry |
| subjects | 631/92/577 692/4022/272 692/53 Amino acid oxidase Amino Acid Transport System y Amino acids Animals Antineoplastic Agents - toxicity Blood Cisplatin Cisplatin - toxicity Creatinine D-Amino-acid oxidase D-Amino-Acid Oxidase - metabolism D-Serine Enantiomers Humanities and Social Sciences Kidney diseases Kidney Diseases - blood Kidney Diseases - chemically induced Kidney Diseases - pathology Kidney Tubules, Proximal - injuries Kidney Tubules, Proximal - metabolism Kidneys L-Serine Male Mice Mice, Inbred C57BL multidisciplinary Proximal tubules Renal tubules Science Science (multidisciplinary) Serine - blood Serine - urine Stereoisomerism Transcription Urine |
| title | Serum d-serine accumulation after proximal renal tubular damage involves neutral amino acid transporter Asc-1 |
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