Journal Article

PreJuSER-32540

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Involvement of integrins in osmosensing and signaling towards autophagic proteolysis in rat liver

vom Dahl, S. ; Schliess, F. ; Reissmann, R. ; Görg, B. ; Weiergräber, O.FZJ* ; Kocalkova, M. ; Dombrowski, F. ; Häussinger, D.

2003
Soc. Bethesda, Md.

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Please use a persistent id in citations: http://hdl.handle.net/2128/2651  doi:10.1074/jbc.M210699200

Abstract: Inhibition of autophagic proteolysis by hypoosmotic or amino acid-induced hepatocyte swelling requires osmosignaling toward p38MAPK; however, the upstream osmosensing and signaling events are unknown. These were studied in the intact perfused rat liver with a preserved in situ environment of hepatocytes. It was found that hypoosmotic hepatocyte swelling led to an activation of Src (but not FAK), Erks, and p38MAPK, which was prevented by the integrin inhibitory hexapeptide GRGDSP, but not its inactive analogue GRGESP. Src inhibition by PP-2 prevented hypoosmotic MAP kinase activation, indicating that the integrin/Src system is located upstream in the osmosignaling toward p38MAPK and Erks. Inhibition of the integrin/Src system by the RGD motif-containing peptide or PP-2 also prevented the inhibition of proteolysis and the decrease in autophagic vacuole volume, which is otherwise observed in response to hypoosmotic or glutamine/glycine-induced hepatocyte swelling. These inhibitors, however, did not affect swelling-independent proteolysis inhibition by phenylalanine. In line with a role of p38MAPK in triggering the volume regulatory decrease (RVD), PP-2 and the RGD peptide blunted RVD in response to hypoosmotic cell swelling. The data identify integrins and Src as upstream events in the osmosignaling toward MAP kinases, proteolysis, and RVD. They further point to a role of integrins as osmo- and mechanosensors in the intact liver, which may provide a link between cell volume and cell function.

Keyword(s): Animals (MeSH) ; Autophagy (MeSH) ; Cell Size: drug effects (MeSH) ; Cell Size: physiology (MeSH) ; Cells, Cultured (MeSH) ; Hepatocytes: cytology (MeSH) ; Hepatocytes: drug effects (MeSH) ; Hepatocytes: physiology (MeSH) ; Integrins: antagonists & inhibitors (MeSH) ; Integrins: physiology (MeSH) ; Liver: drug effects (MeSH) ; Liver: physiology (MeSH) ; Liver: ultrastructure (MeSH) ; MAP Kinase Signaling System (MeSH) ; Male (MeSH) ; Mitogen-Activated Protein Kinases: metabolism (MeSH) ; Models, Biological (MeSH) ; Oligopeptides: pharmacology (MeSH) ; Perfusion (MeSH) ; Rats (MeSH) ; Rats, Wistar (MeSH) ; Signal Transduction (MeSH) ; Water-Electrolyte Balance: physiology (MeSH) ; p38 Mitogen-Activated Protein Kinases (MeSH) ; src-Family Kinases: antagonists & inhibitors (MeSH) ; src-Family Kinases: metabolism (MeSH) ; Integrins ; Oligopeptides ; glycyl-arginyl-glycyl-aspartyl-seryl-proline ; arginyl-glycyl-aspartic acid ; glycyl-arginyl-glycyl-glutamyl-seryl-proline ; src-Family Kinases ; Mitogen-Activated Protein Kinases ; p38 Mitogen-Activated Protein Kinases ; J

Note: Record converted from VDB: 12.11.2012

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Contributing Institute(s):

1. Biologische Strukturforschung (IBI-2)

Research Program(s):

1. Neurowissenschaften (L01)

Appears in the scientific report 2003

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Database coverage:

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