Basic-liver, pancreas, and biliary tractInvolvement of integrins and Src in tauroursodeoxycholate-induced and swelling-induced choleresis☆
Section snippets
Materials
The integrin antagonistic GRGDSP and the inactive control peptide (GRGESP) were from Bachem (Heidelberg, Germany). PP-2 was from Calbiochem-Novabiochem GmbH (Darmstadt, Germany). The antibodies raised against total and phospho-ERK-1/ERK-2 were from Upstate (Charlottesville, VA). Antibodies recognizing FAK (pY397), Src (pY418), Src (pY529), and total Src were from Biosource (Camarillo, CA). Anti-phosphop38MAPK (pTA80/p4A82) antibody was from Promega (Madison, WI). The phospho-specific antibody
Integrin and Src dependence of TUDC-induced signaling toward MAPKs
Rat livers were single-pass perfused with a medium containing TC (100 μmol/L). After 50 minutes of preperfusion with TC (t = 0 minute) (i.e., when steady-state conditions of TC excretion into bile were obtained), TUDC (20 μmol/L) was added. In line with previous data,6, 10, 11 TUDC induced an activation of ERKs and p38MAPK (Figure 1A and B). As shown recently, no effect on MAPK activities was found in control experiments (i.e., without addition of TUDC).6 Interestingly, TUDC also increased the
Role of integrins and Src in TUDC-induced choleresis
Integrins comprise a family of cell-surface glycoproteins that act as receptors for extracellular matrix proteins or membrane-bound counterreceptors on other cells. Integrins are cytoskeleton-linked αβ-heterodimers and are engaged not only in cell adhesion but also in cell signaling (for review, see Aplin et al.32). In normal liver, the most important integrins are α1β1, α5β1, and α9β1.36, 37, 38 Signal transduction by integrins primarily occurs in the context of highly organized and dynamic
References (50)
- et al.
Ursodeoxycholic acid in primary biliary cirrhosisresults of a controlled double-blind trial
Gastroenterology
(1989) - et al.
Ursodeoxycholic acid in the treatment of primary biliary cirrhosis
Gastroenterology
(1994) - et al.
Tauroursodesoxycholate-induced choleresis involves p38MAPK activation and translocation of the bile salt export pump
Gastroenterology
(2001) - et al.
Tauroursodeoxycholate prevents taurocholate induced cholestasis
Life Sci
(1982) - et al.
Mitogen-activated protein kinases mediate the stimulation of bile acid secretion by tauroursodeoxycholate in rat liver
Gastroenterology
(1997) - et al.
Taurolithocholic acid-3 sulfate induces CD95 trafficking and apoptosis in a c-Jun kinase-dependent manner
Gastroenterology
(2002) - et al.
Molecular aspects of membrane stabilization by ursodeoxycholate
Gastroenterology
(1993) - et al.
Conjugates of ursodeoxycholate protect against cholestasis and hepatocellular necrosis caused by more hydrophobic bile salts. In vivo studies in the rat
Gastroenterology
(1991) - et al.
Hepatoprotection by hydrophilic bile salts
J Hepatol
(1994) - et al.
Regulation of taurocholate excretion by a hypo-osmolarity-activated signal transduction pathway in rat liver
Gastroenterology
(1996)
Regulation of the dynamic localization of the Bsep gene encoded bile salt export pump by anisoosmolarity
Hepatology
Cell swelling-induced translocation of rat liver Na+/taurocholate cotransport polypeptide is mediated via the phosphoinositide 3-kinase signaling pathway
J Biol Chem
Protein kinase B/Akt mediates cAMP- and cell swelling-stimulated Na+/taurocholate cotransport and Ntcp translocation
J Biol Chem
Osmodependent dynamic localization of the multidrug resistance protein 2 in the rat hepatocyte canalicular membrane
Gastroenterology
Tauroursodeoxycholic acid inserts the apical conjugte export pump Mrp2 into canalicular membranes and stimulates organic anion secretion by protein kinase C-dependent mechanisms in cholestatic rat liver
Hepatology
The use of perfusion of liver and other organs for the study of microsomal electron-transport and cytochrome P-450 systems
Methods Enzymol
Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor
J Biol Chem
Regulation, substrates and functions of src
Biochim Biophys Acta
Discovery of a novel, potent, and Src family-selective tyrosine kinase inhibitor. Study of Lck- and FynT-dependent T cell activation
J Biol Chem
Involvement of p38MAPK in the regulation of proteolysis by liver cell hydration
Gastroenterology
The integrin α6β1 is necessary for the matrix-dependent activation of FAK and MAPK and the migration of human hepatocellular carcinoma cells
Hepatology
Proteolysis of integrin α5 and β1 subunits involved in retinoic acid-induced apoptosis in human hepatoma Hep3B cells
Cancer Lett
Autocrine motility factor enhances hepatoma cell invasion across the basement membrane through activation of β1 integrins
Hepatology
Focal adhesion kinase overexpression enhances Ras-dependent integrin signaling to Erk2/mitogen-activated protein kinase through interactions with and activation of c-Src
J Biol Chem
Phosphorylation of tyrosine 397 in focal adhesion kinase is required for binding phosphatidylinositol-3-kinase
J Biol Chem
Cited by (100)
Role of the microbiota–gut–heart axis between bile acids and cardiovascular disease
2024, Biomedicine and PharmacotherapyThe potent role of Src kinase-regulating glucose metabolism in cancer
2022, Biochemical PharmacologyTUDCA receptors and their role on pancreatic beta cells
2021, Progress in Biophysics and Molecular BiologyEASL recognition award recipient 2021: Prof. Dieter Häussinger
2021, Journal of HepatologyPharmacology of bile acid receptors: Evolution of bile acids from simple detergents to complex signaling molecules
2016, Pharmacological Research
- ☆
Supported by Deutsche Forschungsgemeinschaft through Sonderforschungsbereich 575 “Experimentelle Hepatologie” Düsseldorf.
- 1
The authors thank Nicole Eichhorst, Claudia Holneicher, Markus Mroz, and Dr. Nirmalendu Saha for expert technical assistance.