Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus
Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2015-12, Vol.5 (1), p.18311-18311, Article 18311 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 18311 |
|---|---|
| container_issue | 1 |
| container_start_page | 18311 |
| container_title | Scientific reports |
| container_volume | 5 |
| creator | Khositseth, Sookkasem Uawithya, Panapat Somparn, Poorichaya Charngkaew, Komgrid Thippamom, Nattakan Hoffert, Jason D. Saeed, Fahad Michael Payne, D. Chen, Shu-Hui Fenton, Robert A. Pisitkun, Trairak |
| description | Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI. |
| doi_str_mv | 10.1038/srep18311 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4682130</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>4103259371</sourcerecordid><originalsourceid>FETCH-LOGICAL-c438t-9c326c557dcb17d63f321e68846741c32c8cf2ed5a2c3d55ea1f662889fc2c693</originalsourceid><addsrcrecordid>eNplkUtr3DAUhUVpaUKaRf9AEXTTFpzqbXlTCKGPQCCbdC000rVHqS05kh2Yf1-FSYdpq80VnI9zz-Ug9JaSC0q4_lwyzFRzSl-gU0aEbBhn7OXR_wSdl3JP6pOsE7R7jU6YUq1QhJ2i6XJd0ry1Q3DYw5Ctt0tIEace24fVzimH2DAcCrYRg83jDsMjxAWHiLe7Of2yI0zBNiH61YHHEeZtTgPEJ79gN7BAqWwJc_BreYNe9XYscP48z9DPb1_vrn40N7ffr68ubxonuF6aznGmnJStdxvaesV7zigorUWNTavotOsZeGmZ415KsLRXimnd9Y451fEz9GXvO6-bCbyrgbMdzZzDZPPOJBvM30oMWzOkRyOUZpSTavDh2SCnhxXKYqZQHIyjjZDWYmgrieBEs7ai7_9B79OaYz3PUE0IpVJoUamPe8rlVGpl_SEMJeapR3PosbLvjtMfyD-tVeDTHihVigPko5X_uf0G5xyonw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1800115484</pqid></control><display><type>article</type><title>Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus</title><source>Nature Open Access</source><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals</source><source>PubMed Central</source><source>Springer Nature OA/Free Journals</source><source>Free Full-Text Journals in Chemistry</source><creator>Khositseth, Sookkasem ; Uawithya, Panapat ; Somparn, Poorichaya ; Charngkaew, Komgrid ; Thippamom, Nattakan ; Hoffert, Jason D. ; Saeed, Fahad ; Michael Payne, D. ; Chen, Shu-Hui ; Fenton, Robert A. ; Pisitkun, Trairak</creator><creatorcontrib>Khositseth, Sookkasem ; Uawithya, Panapat ; Somparn, Poorichaya ; Charngkaew, Komgrid ; Thippamom, Nattakan ; Hoffert, Jason D. ; Saeed, Fahad ; Michael Payne, D. ; Chen, Shu-Hui ; Fenton, Robert A. ; Pisitkun, Trairak</creatorcontrib><description>Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep18311</identifier><identifier>PMID: 26674602</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>14/19 ; 14/28 ; 14/34 ; 38/77 ; 692/308/1426 ; 692/4022/1585/1 ; 82/1 ; Actin ; Actin Cytoskeleton - metabolism ; Animals ; Aquaporin 2 ; Aquaporin 2 - metabolism ; Autophagy ; Biodegradation ; Cell adhesion ; Cell adhesion & migration ; Chromatography, Liquid ; Cytoskeleton ; Diabetes ; Diabetes insipidus ; Diabetes Insipidus, Nephrogenic - metabolism ; Diabetes Insipidus, Nephrogenic - physiopathology ; Electron microscopy ; Humanities and Social Sciences ; Hypokalemia ; Hypokalemia - metabolism ; Hypokalemia - physiopathology ; Immunoblotting ; Immunofluorescence ; Kidney Medulla - metabolism ; Kidney Tubules, Collecting - metabolism ; Kidney Tubules, Collecting - ultrastructure ; Localization ; Lysosomal Membrane Proteins - metabolism ; Male ; Mass spectrometry ; Mass spectroscopy ; Metabolites ; Microscopy, Immunoelectron ; Microtubule-Associated Proteins - metabolism ; multidisciplinary ; Phagosomes ; Phagosomes - metabolism ; Phagosomes - ultrastructure ; Potassium ; Proteins ; Proteome - metabolism ; Proteomics - methods ; Rats, Sprague-Dawley ; Rodents ; Science ; Tandem Mass Spectrometry ; Time Factors</subject><ispartof>Scientific reports, 2015-12, Vol.5 (1), p.18311-18311, Article 18311</ispartof><rights>The Author(s) 2015</rights><rights>Copyright Nature Publishing Group Dec 2015</rights><rights>Copyright © 2015, Macmillan Publishers Limited 2015 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c438t-9c326c557dcb17d63f321e68846741c32c8cf2ed5a2c3d55ea1f662889fc2c693</citedby><cites>FETCH-LOGICAL-c438t-9c326c557dcb17d63f321e68846741c32c8cf2ed5a2c3d55ea1f662889fc2c693</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/PMC4682130/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4682130/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,728,781,785,865,886,27929,27930,41125,42194,51581,53796,53798</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26674602$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Khositseth, Sookkasem</creatorcontrib><creatorcontrib>Uawithya, Panapat</creatorcontrib><creatorcontrib>Somparn, Poorichaya</creatorcontrib><creatorcontrib>Charngkaew, Komgrid</creatorcontrib><creatorcontrib>Thippamom, Nattakan</creatorcontrib><creatorcontrib>Hoffert, Jason D.</creatorcontrib><creatorcontrib>Saeed, Fahad</creatorcontrib><creatorcontrib>Michael Payne, D.</creatorcontrib><creatorcontrib>Chen, Shu-Hui</creatorcontrib><creatorcontrib>Fenton, Robert A.</creatorcontrib><creatorcontrib>Pisitkun, Trairak</creatorcontrib><title>Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.</description><subject>14/19</subject><subject>14/28</subject><subject>14/34</subject><subject>38/77</subject><subject>692/308/1426</subject><subject>692/4022/1585/1</subject><subject>82/1</subject><subject>Actin</subject><subject>Actin Cytoskeleton - metabolism</subject><subject>Animals</subject><subject>Aquaporin 2</subject><subject>Aquaporin 2 - metabolism</subject><subject>Autophagy</subject><subject>Biodegradation</subject><subject>Cell adhesion</subject><subject>Cell adhesion & migration</subject><subject>Chromatography, Liquid</subject><subject>Cytoskeleton</subject><subject>Diabetes</subject><subject>Diabetes insipidus</subject><subject>Diabetes Insipidus, Nephrogenic - metabolism</subject><subject>Diabetes Insipidus, Nephrogenic - physiopathology</subject><subject>Electron microscopy</subject><subject>Humanities and Social Sciences</subject><subject>Hypokalemia</subject><subject>Hypokalemia - metabolism</subject><subject>Hypokalemia - physiopathology</subject><subject>Immunoblotting</subject><subject>Immunofluorescence</subject><subject>Kidney Medulla - metabolism</subject><subject>Kidney Tubules, Collecting - metabolism</subject><subject>Kidney Tubules, Collecting - ultrastructure</subject><subject>Localization</subject><subject>Lysosomal Membrane Proteins - metabolism</subject><subject>Male</subject><subject>Mass spectrometry</subject><subject>Mass spectroscopy</subject><subject>Metabolites</subject><subject>Microscopy, Immunoelectron</subject><subject>Microtubule-Associated Proteins - metabolism</subject><subject>multidisciplinary</subject><subject>Phagosomes</subject><subject>Phagosomes - metabolism</subject><subject>Phagosomes - ultrastructure</subject><subject>Potassium</subject><subject>Proteins</subject><subject>Proteome - metabolism</subject><subject>Proteomics - methods</subject><subject>Rats, Sprague-Dawley</subject><subject>Rodents</subject><subject>Science</subject><subject>Tandem Mass Spectrometry</subject><subject>Time Factors</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkUtr3DAUhUVpaUKaRf9AEXTTFpzqbXlTCKGPQCCbdC000rVHqS05kh2Yf1-FSYdpq80VnI9zz-Ug9JaSC0q4_lwyzFRzSl-gU0aEbBhn7OXR_wSdl3JP6pOsE7R7jU6YUq1QhJ2i6XJd0ry1Q3DYw5Ctt0tIEace24fVzimH2DAcCrYRg83jDsMjxAWHiLe7Of2yI0zBNiH61YHHEeZtTgPEJ79gN7BAqWwJc_BreYNe9XYscP48z9DPb1_vrn40N7ffr68ubxonuF6aznGmnJStdxvaesV7zigorUWNTavotOsZeGmZ415KsLRXimnd9Y451fEz9GXvO6-bCbyrgbMdzZzDZPPOJBvM30oMWzOkRyOUZpSTavDh2SCnhxXKYqZQHIyjjZDWYmgrieBEs7ai7_9B79OaYz3PUE0IpVJoUamPe8rlVGpl_SEMJeapR3PosbLvjtMfyD-tVeDTHihVigPko5X_uf0G5xyonw</recordid><startdate>20151217</startdate><enddate>20151217</enddate><creator>Khositseth, Sookkasem</creator><creator>Uawithya, Panapat</creator><creator>Somparn, Poorichaya</creator><creator>Charngkaew, Komgrid</creator><creator>Thippamom, Nattakan</creator><creator>Hoffert, Jason D.</creator><creator>Saeed, Fahad</creator><creator>Michael Payne, D.</creator><creator>Chen, Shu-Hui</creator><creator>Fenton, Robert A.</creator><creator>Pisitkun, Trairak</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>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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151217</creationdate><title>Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus</title><author>Khositseth, Sookkasem ; Uawithya, Panapat ; Somparn, Poorichaya ; Charngkaew, Komgrid ; Thippamom, Nattakan ; Hoffert, Jason D. ; Saeed, Fahad ; Michael Payne, D. ; Chen, Shu-Hui ; Fenton, Robert A. ; Pisitkun, Trairak</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c438t-9c326c557dcb17d63f321e68846741c32c8cf2ed5a2c3d55ea1f662889fc2c693</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>14/19</topic><topic>14/28</topic><topic>14/34</topic><topic>38/77</topic><topic>692/308/1426</topic><topic>692/4022/1585/1</topic><topic>82/1</topic><topic>Actin</topic><topic>Actin Cytoskeleton - metabolism</topic><topic>Animals</topic><topic>Aquaporin 2</topic><topic>Aquaporin 2 - metabolism</topic><topic>Autophagy</topic><topic>Biodegradation</topic><topic>Cell adhesion</topic><topic>Cell adhesion & migration</topic><topic>Chromatography, Liquid</topic><topic>Cytoskeleton</topic><topic>Diabetes</topic><topic>Diabetes insipidus</topic><topic>Diabetes Insipidus, Nephrogenic - metabolism</topic><topic>Diabetes Insipidus, Nephrogenic - physiopathology</topic><topic>Electron microscopy</topic><topic>Humanities and Social Sciences</topic><topic>Hypokalemia</topic><topic>Hypokalemia - metabolism</topic><topic>Hypokalemia - physiopathology</topic><topic>Immunoblotting</topic><topic>Immunofluorescence</topic><topic>Kidney Medulla - metabolism</topic><topic>Kidney Tubules, Collecting - metabolism</topic><topic>Kidney Tubules, Collecting - ultrastructure</topic><topic>Localization</topic><topic>Lysosomal Membrane Proteins - metabolism</topic><topic>Male</topic><topic>Mass spectrometry</topic><topic>Mass spectroscopy</topic><topic>Metabolites</topic><topic>Microscopy, Immunoelectron</topic><topic>Microtubule-Associated Proteins - metabolism</topic><topic>multidisciplinary</topic><topic>Phagosomes</topic><topic>Phagosomes - metabolism</topic><topic>Phagosomes - ultrastructure</topic><topic>Potassium</topic><topic>Proteins</topic><topic>Proteome - metabolism</topic><topic>Proteomics - methods</topic><topic>Rats, Sprague-Dawley</topic><topic>Rodents</topic><topic>Science</topic><topic>Tandem Mass Spectrometry</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Khositseth, Sookkasem</creatorcontrib><creatorcontrib>Uawithya, Panapat</creatorcontrib><creatorcontrib>Somparn, Poorichaya</creatorcontrib><creatorcontrib>Charngkaew, Komgrid</creatorcontrib><creatorcontrib>Thippamom, Nattakan</creatorcontrib><creatorcontrib>Hoffert, Jason D.</creatorcontrib><creatorcontrib>Saeed, Fahad</creatorcontrib><creatorcontrib>Michael Payne, D.</creatorcontrib><creatorcontrib>Chen, Shu-Hui</creatorcontrib><creatorcontrib>Fenton, Robert A.</creatorcontrib><creatorcontrib>Pisitkun, Trairak</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 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>MEDLINE - Academic</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>Khositseth, Sookkasem</au><au>Uawithya, Panapat</au><au>Somparn, Poorichaya</au><au>Charngkaew, Komgrid</au><au>Thippamom, Nattakan</au><au>Hoffert, Jason D.</au><au>Saeed, Fahad</au><au>Michael Payne, D.</au><au>Chen, Shu-Hui</au><au>Fenton, Robert A.</au><au>Pisitkun, Trairak</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2015-12-17</date><risdate>2015</risdate><volume>5</volume><issue>1</issue><spage>18311</spage><epage>18311</epage><pages>18311-18311</pages><artnum>18311</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Hypokalemia (low serum potassium level) is a common electrolyte imbalance that can cause a defect in urinary concentrating ability, i.e., nephrogenic diabetes insipidus (NDI), but the molecular mechanism is unknown. We employed proteomic analysis of inner medullary collecting ducts (IMCD) from rats fed with a potassium-free diet for 1 day. IMCD protein quantification was performed by mass spectrometry using a label-free methodology. A total of 131 proteins, including the water channel AQP2, exhibited significant changes in abundance, most of which were decreased. Bioinformatic analysis revealed that many of the down-regulated proteins were associated with the biological processes of generation of precursor metabolites and energy, actin cytoskeleton organization and cell-cell adhesion. Targeted LC-MS/MS and immunoblotting studies further confirmed the down regulation of 18 selected proteins. Electron microscopy showed autophagosomes/autophagolysosomes in the IMCD cells of rats deprived of potassium for only 1 day. An increased number of autophagosomes was also confirmed by immunofluorescence, demonstrating co-localization of LC3 and Lamp1 with AQP2 and several other down-regulated proteins in IMCD cells. AQP2 was also detected in autophagosomes in IMCD cells of potassium-deprived rats by immunogold electron microscopy. Thus, enhanced autophagic degradation of proteins, most notably including AQP2, is an early event in hypokalemia-induced NDI.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>26674602</pmid><doi>10.1038/srep18311</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2015-12, Vol.5 (1), p.18311-18311, Article 18311 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4682130 |
| source | Nature Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central; Springer Nature OA/Free Journals; Free Full-Text Journals in Chemistry |
| subjects | 14/19 14/28 14/34 38/77 692/308/1426 692/4022/1585/1 82/1 Actin Actin Cytoskeleton - metabolism Animals Aquaporin 2 Aquaporin 2 - metabolism Autophagy Biodegradation Cell adhesion Cell adhesion & migration Chromatography, Liquid Cytoskeleton Diabetes Diabetes insipidus Diabetes Insipidus, Nephrogenic - metabolism Diabetes Insipidus, Nephrogenic - physiopathology Electron microscopy Humanities and Social Sciences Hypokalemia Hypokalemia - metabolism Hypokalemia - physiopathology Immunoblotting Immunofluorescence Kidney Medulla - metabolism Kidney Tubules, Collecting - metabolism Kidney Tubules, Collecting - ultrastructure Localization Lysosomal Membrane Proteins - metabolism Male Mass spectrometry Mass spectroscopy Metabolites Microscopy, Immunoelectron Microtubule-Associated Proteins - metabolism multidisciplinary Phagosomes Phagosomes - metabolism Phagosomes - ultrastructure Potassium Proteins Proteome - metabolism Proteomics - methods Rats, Sprague-Dawley Rodents Science Tandem Mass Spectrometry Time Factors |
| title | Autophagic degradation of aquaporin-2 is an early event in hypokalemia-induced nephrogenic diabetes insipidus |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-15T09%3A11%3A11IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Autophagic%20degradation%20of%20aquaporin-2%20is%20an%20early%20event%20in%20hypokalemia-induced%20nephrogenic%20diabetes%20insipidus&rft.jtitle=Scientific%20reports&rft.au=Khositseth,%20Sookkasem&rft.date=2015-12-17&rft.volume=5&rft.issue=1&rft.spage=18311&rft.epage=18311&rft.pages=18311-18311&rft.artnum=18311&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep18311&rft_dat=%3Cproquest_pubme%3E4103259371%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1800115484&rft_id=info:pmid/26674602&rfr_iscdi=true |