title: Low pH enhances connexin32 degradation in the pancreatic acinar cell.
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. 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.
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut; anamika.reed@yale.edu.
authors.forename: Anamika M
authors.initials: AM
authors.lastname: Reed
authors.affiliation: Veterans Affairs Healthcare System, West Haven, Connecticut; and.
authors.forename: Thomas
authors.initials: T
authors.lastname: Kolodecik
authors.affiliation: Division of Pediatric Gastroenterology, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania.
authors.forename: Sohail Z
authors.initials: SZ
authors.lastname: Husain
authors.affiliation: Section of Digestive Diseases, Department of Internal Medicine, Yale University, New Haven, Connecticut; Veterans Affairs Healthcare System, West Haven, Connecticut; and.
authors.forename: Fred S
authors.initials: FS
authors.lastname: Gorelick
mesh_terms: D061354:Acinar Cells / Q000378:metabolism*; D000818:Animals; D001343:Autophagy; D020013:Calcium Signaling; D002450:Cell Communication; D017630:Connexins / Q000378:metabolism*; D015536:Down-Regulation; D017629:Gap Junctions / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D008247:Lysosomes / Q000378:metabolism; D046790:Pancreas, Exocrine / Q000378:metabolism*; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D059748:Proteolysis; D051381:Rats; D013997:Time Factors; D000097002:Gap Junction beta-1 Protein
chemical_list: D017630:Connexins; D046988:Proteasome Endopeptidase Complex; D000097002:Gap Junction beta-1 Protein
keywords: acinar cell; cell pH; cell-cell interaction; gap junctions; pancreas; protein degradation