Glucose modulates Pax6 expression through the JNK/p38 MAP kinase pathway in pancreatic beta-cells
| Autor: | Arun Kannan, Mohanraj Sadasivam, Antojenifer Panneerselvam, Chidambaram Prahalathan, Sivasangari Balakrishnan |
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| Rok vydání: | 2014 |
| Předmět: |
MAPK/ERK pathway
endocrine system PAX6 Transcription Factor MAP Kinase Signaling System Down-Regulation Biology Mitogen-activated protein kinase kinase p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Cell Line Tumor Insulin-Secreting Cells medicine Staurosporine Animals Paired Box Transcription Factors Calcium Signaling General Pharmacology Toxicology and Pharmaceutics Phosphorylation RNA Small Interfering Protein kinase A Eye Proteins Homeodomain Proteins MAP kinase kinase kinase Kinase PTEN Phosphohydrolase General Medicine Transfection Cell biology Rats Repressor Proteins Glucose Insulinoma RNA Interference Signal transduction medicine.drug |
| Zdroj: | Life sciences. 109(1) |
| ISSN: | 1879-0631 |
| Popis: | Aim The paired and homeodomain-containing transcription factor, paired box 6 (Pax6), has shown to play pivotal roles in beta-cell function, including cell survival, insulin biosynthesis and secretion. The present study investigates the signaling events that regulate the modulation of Pax6 expression by glucose and the role of this modulation in cell survival in rat insulinoma-1E (INS-1E) cells. Main methods INS-1E cells were incubated on 1 mM (low) or 25 mM (high) glucose overnight. To elucidate the signaling pathways that regulate Pax6 expression, we utilized specific inhibitors. The siRNA transfection of Pax6 into INS-1E cells was performed by electroporation. The mRNA and protein levels were determined by real-time PCR and Western blotting, respectively. Key findings We found that the mRNA and protein levels of Pax6 were reduced by approximately 4-fold in high, compared to low, glucose-treated cells. Staurosporine, the c-Jun N-terminal kinase (JNK) inhibitor SP600125 and the p38 mitogen-activated protein kinase (p38 MAPK) inhibitor SB203580 significantly increased Pax6 levels in high glucose-treated INS-1E cells compared to their respective controls. However, neither calcium ionophore nor the extracellular signal-regulated kinase (ERK) inhibitor U0126 resulted in any alteration in Pax6 protein expression. Further, a siRNA-mediated knockdown of Pax6 significantly decreased the expression of tumor-suppressor phosphatase with tensin homology (PTEN) while increasing cell viability in low glucose-treated INS-1E cells. Significance This study addresses the signaling events that regulate the glucose-dependent expression of Pax6 and the role of these events in cell survival in pancreatic beta cells. |
| Databáze: | OpenAIRE |
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