Regulation of AP-1 activity in glucose-stimulated insulinoma cells.

Abstract

The transcriptional activity of AP-1 has been analyzed in glucose-stimulated INS-1 insulinoma cells using a chromosomally embedded AP-1-responsive reporter gene. We show that AP-1 activity was significantly elevated in glucose-treated INS-1 cells. Preincubation of the cells with nifedipine or expression of the Ca(2+) binding protein parvalbumin in the cytoplasm of INS-1 cells reduced AP-1 activity. Thus, activation of L-type Ca(2+) channels and an elevated cytoplasmic Ca(2+) concentration are crucial to connecting glucose stimulation with enhanced AP-1 activity. Expression of dominant negative forms of A-Raf, MKK4 or MKK6 and pharmacological inhibition of MEK and p38 revealed that extracellular signal-regulated protein kinase, p38 and c-Jun NH(2)-terminal protein kinase participate in the upregulation of AP-1 activity. Expression of dominant-negative mutants of c-Jun and Elk-1 reduced AP-1 transcriptional activity in INS-1 cells indicating that c-Jun and ternary complex factors are involved in the regulation of AP-1 activity in glucose-stimulated insulinoma cells.

• Authors: Isabelle Müller, Takeshi Endo, Gerald Thiel
• Journal: Journal of cellular biochemistry (J Cell Biochem) Vol. 110 Issue 6 Pg. 1481-94 (Aug 15 2010) ISSN: 1097-4644 [Electronic] United States
• PMID: 20503247 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: (c) 2010 Wiley-Liss, Inc.

Chemical References

• Calcium Channel Blockers
• Calcium Channels, L-Type
• Parvalbumins
• Transcription Factor AP-1
• ets-Domain Protein Elk-1
• JNK Mitogen-Activated Protein Kinases
• Mitogen-Activated Protein Kinase 1
• Mitogen-Activated Protein Kinase 3
• p38 Mitogen-Activated Protein Kinases
• MAP Kinase Kinase 4
• Nifedipine
• Glucose
• Calcium

Topics

• Animals
• Blotting, Western
• Calcium (metabolism)
• Calcium Channel Blockers (pharmacology)
• Calcium Channels, L-Type (metabolism)
• Cell Line, Tumor
• Enzyme Activation (drug effects)
• Glucose (pharmacology)
• Insulin-Secreting Cells (drug effects, metabolism)
• Insulinoma (genetics, metabolism, pathology)
• JNK Mitogen-Activated Protein Kinases (genetics, metabolism)
• MAP Kinase Kinase 4 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 1 (genetics, metabolism)
• Mitogen-Activated Protein Kinase 3 (genetics, metabolism)
• Mutation
• Nifedipine (pharmacology)
• Parvalbumins (genetics, metabolism)
• Phosphorylation
• Signal Transduction (drug effects)
• Transcription Factor AP-1 (genetics, metabolism)
• Up-Regulation
• ets-Domain Protein Elk-1 (genetics, metabolism)
• p38 Mitogen-Activated Protein Kinases (genetics, metabolism)