Low pH enhances connexin32 degradation in the pancreatic acinar cell
Decreased extracellular pH is observed in a number of clinical conditions and can sensitize to the development and worsen the severity of acute pancreatitis. Because intercellular communication through gap junctions is pH-sensitive and modulates pancreatitis responses, we evaluated the effects of lo...
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| Veröffentlicht in: | American journal of physiology: Gastrointestinal and liver physiology 2014-07, Vol.307 (1), p.G24-G32 |
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| container_end_page | G32 |
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| container_issue | 1 |
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| container_title | American journal of physiology: Gastrointestinal and liver physiology |
| container_volume | 307 |
| creator | Reed, Anamika M Kolodecik, Thomas Husain, Sohail Z Gorelick, Fred S |
| description | Decreased extracellular pH is observed in a number of clinical conditions and can sensitize to the development and worsen the severity of acute pancreatitis. Because intercellular communication through gap junctions is pH-sensitive and modulates pancreatitis responses, we evaluated the effects of low pH on gap junctions in the rat pancreatic acinar cell. Decreasing extracellular pH from 7.4 to 7.0 significantly inhibited gap junctional intracellular communication. Acidic pH also significantly reduced levels of connexin32, the predominant gap junction protein in acinar cells, and altered its localization. Increased degradation through the proteasomal, lysosomal, and autophagic pathways mediated the decrease in connexin32 under low-pH conditions. These findings provide the first evidence that low extracellular pH can regulate gap junctional intercellular communication by enhancing connexin degradation. |
| doi_str_mv | 10.1152/ajpgi.00010.2014 |
| format | Article |
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Because intercellular communication through gap junctions is pH-sensitive and modulates pancreatitis responses, we evaluated the effects of low pH on gap junctions in the rat pancreatic acinar cell. Decreasing extracellular pH from 7.4 to 7.0 significantly inhibited gap junctional intracellular communication. Acidic pH also significantly reduced levels of connexin32, the predominant gap junction protein in acinar cells, and altered its localization. Increased degradation through the proteasomal, lysosomal, and autophagic pathways mediated the decrease in connexin32 under low-pH conditions. These findings provide the first evidence that low extracellular pH can regulate gap junctional intercellular communication by enhancing connexin degradation.</description><subject>Acidity</subject><subject>Acinar Cells - metabolism</subject><subject>Alkalinity</subject><subject>Animals</subject><subject>Autophagy</subject><subject>Calcium Signaling</subject><subject>Cell Communication</subject><subject>Cells</subject><subject>Connexins - metabolism</subject><subject>Down-Regulation</subject><subject>Gap Junction beta-1 Protein</subject><subject>Gap Junctions - metabolism</subject><subject>Hydrogen-Ion Concentration</subject><subject>Lysosomes - metabolism</subject><subject>Pancreas</subject><subject>Pancreas, Exocrine - metabolism</subject><subject>Proteasome Endopeptidase Complex - metabolism</subject><subject>Proteins</subject><subject>Proteolysis</subject><subject>Rats</subject><subject>Time Factors</subject><issn>0193-1857</issn><issn>1522-1547</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkc1PAyEQxYnR2Fq9ezIkXrxsBRYovZiY-lGTJl70TCjLtjRbWGHXj_9etq2NeiLM_Gby3jwAzjEaYszItVrVCztECKUCQZgegH4qkwwzOjoEfYTHeYYFG_XASYyrxDGC8THoESowQYz1wd3Mf8B6Co1bKqdNhNo7Zz6tywkszCKoQjXWO2gdbJYG1gkKJpU0VNo6FaA2VXUKjkpVRXO2ewfg9eH-ZTLNZs-PT5PbWaYpoU1SIualJrgwvCjzXDMmxlQnUcwgwdMPFxqNqNJM54aXghPM5jopUIJQrIt8AG62e-t2vjaFNq4JqpJ1sGsVvqRXVv7tOLuUC_8uKRIIc5IWXO0WBP_WmtjItY2dA-WMb6NMdyOc5XzME3r5D135Nrhkr6NourKg40ShLaWDjzGYci8GI9lFJDcRyU1EsosojVz8NrEf-Mkk_waDwYzs</recordid><startdate>20140701</startdate><enddate>20140701</enddate><creator>Reed, Anamika M</creator><creator>Kolodecik, Thomas</creator><creator>Husain, Sohail Z</creator><creator>Gorelick, Fred S</creator><general>American Physiological Society</general><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>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140701</creationdate><title>Low pH enhances connexin32 degradation in the pancreatic acinar cell</title><author>Reed, Anamika M ; Kolodecik, Thomas ; Husain, Sohail Z ; Gorelick, Fred S</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c424t-188bfc21de6df33c55894c0055e0865581dc074ac5c3e6f86215bcadaa8241cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Acidity</topic><topic>Acinar Cells - metabolism</topic><topic>Alkalinity</topic><topic>Animals</topic><topic>Autophagy</topic><topic>Calcium Signaling</topic><topic>Cell Communication</topic><topic>Cells</topic><topic>Connexins - metabolism</topic><topic>Down-Regulation</topic><topic>Gap Junction beta-1 Protein</topic><topic>Gap Junctions - metabolism</topic><topic>Hydrogen-Ion Concentration</topic><topic>Lysosomes - metabolism</topic><topic>Pancreas</topic><topic>Pancreas, Exocrine - metabolism</topic><topic>Proteasome Endopeptidase Complex - metabolism</topic><topic>Proteins</topic><topic>Proteolysis</topic><topic>Rats</topic><topic>Time Factors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Reed, Anamika M</creatorcontrib><creatorcontrib>Kolodecik, Thomas</creatorcontrib><creatorcontrib>Husain, Sohail Z</creatorcontrib><creatorcontrib>Gorelick, Fred S</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Reed, Anamika M</au><au>Kolodecik, Thomas</au><au>Husain, Sohail Z</au><au>Gorelick, Fred S</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Low pH enhances connexin32 degradation in the pancreatic acinar cell</atitle><jtitle>American journal of physiology: Gastrointestinal and liver physiology</jtitle><addtitle>Am J Physiol Gastrointest Liver Physiol</addtitle><date>2014-07-01</date><risdate>2014</risdate><volume>307</volume><issue>1</issue><spage>G24</spage><epage>G32</epage><pages>G24-G32</pages><issn>0193-1857</issn><eissn>1522-1547</eissn><coden>APGPDF</coden><abstract>Decreased extracellular pH is observed in a number of clinical conditions and can sensitize to the development and worsen the severity of acute pancreatitis. 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| source | MEDLINE; American Physiological Society; EZB-FREE-00999 freely available EZB journals; Alma/SFX Local Collection |
| subjects | Acidity Acinar Cells - metabolism Alkalinity Animals Autophagy Calcium Signaling Cell Communication Cells Connexins - metabolism Down-Regulation Gap Junction beta-1 Protein Gap Junctions - metabolism Hydrogen-Ion Concentration Lysosomes - metabolism Pancreas Pancreas, Exocrine - metabolism Proteasome Endopeptidase Complex - metabolism Proteins Proteolysis Rats Time Factors |
| title | Low pH enhances connexin32 degradation in the pancreatic acinar cell |
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