Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ramamoorthy, S; Stepan, V; Todisco, A.
Intracellular mechanisms mediating the anti-apoptotic action of gastrin.
Biochem Biophys Res Commun. 2004; 323(1):44-48
Doi: 10.1016/j.bbrc.2004.08.059
Web of Science
PubMed
FullText
FullText_MUG
- Co-Autor*innen der Med Uni Graz
- Stepan Vinzenz
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- Abstract:
- We previously reported that gastrin (G17) inhibits apoptosis of AR4-2J pancreatic adenocarcinoma cells, through the activation of Akt. We dissected the mechanisms responsible for this effect. D2, a CCKB receptor antagonist, inhibited G17 induction of Akt phosphorylation, measured by Western blots with anti-phospho-Akt antibodies. The intracellular calcium chelator BAPTA-AM, but not the PKC inhibitor GF109203X, blocked G17 induction of Akt. G17 stimulated BAD phosphorylation, measured by both Western blots with anti-phospho-BAD antibodies and by in vitro Akt kinase assays using recombinant BAD as substrate. G17 also induced FOXO3 phosphorylation assessed by Western blots with anti-phospho-FOXO3 antibodies, and BAPTA-AM inhibited this effect. Gastrin inhibited luciferase activity in cells transfected with FOXO1 together with a vector containing insulin-responsive sequences upstream of the luciferase reporter gene. In conclusion, G17 induces Akt through activation of CCKB receptors and of intracellular calcium-dependent, PKC-independent, pathways. This effect leads to BAD phosphorylation and to forkhead transcription factors inactivation.
Copyright 2004 Elsevier Inc. - Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Apoptosis -
- Blotting, Western -
- Calcium - metabolism
- Carrier Proteins - metabolism
- Cell Line -
- Chelating Agents - pharmacology
- DNA-Binding Proteins - metabolism
- Egtazic Acid - analogs and derivatives Egtazic Acid - pharmacology
- Enzyme Inhibitors - pharmacology
- Forkhead Transcription Factors -
- Gastrins - biosynthesis Gastrins - metabolism Gastrins - physiology
- Genes, Reporter -
- Genetic Vectors -
- Immunoprecipitation -
- Indoles - pharmacology
- Luciferases - metabolism
- Maleimides - pharmacology
- Phosphorylation -
- Plasmids - metabolism
- Protein-Serine-Threonine Kinases - metabolism
- Proto-Oncogene Proteins - metabolism
- Proto-Oncogene Proteins c-akt -
- Rats -
- Recombinant Proteins - metabolism
- Transcription Factors - metabolism
- Transcription, Genetic -
- Transfection -
- bcl-Associated Death Protein -
- Find related publications in this database (Keywords)
- cellular apoptosis
- protein kinases
- forkhead/winged-helix transcription factors
- Akt kinase