Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell
| Autor: | Isao Ishii, Ichiro Niki, Toshihide Kimura, Norimichi Itoh, Tatsuhito Umeki, Yasuhito Naito, Hideyuki Yamamoto, Yuka Kimura, Hideo Kimura, Shigeki Taniguchi |
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| Rok vydání: | 2012 |
| Předmět: |
Male
MAPK/ERK pathway Sp1 Transcription Factor Tolbutamide Cystathionine beta-Synthase Gene Expression Biochemistry Mice Endocrinology ELK1 Insulin-Secreting Cells Glyburide Insulin Secretion parasitic diseases Animals Hypoglycemic Agents Insulin Protein phosphorylation Calcium Signaling Hydrogen Sulfide Phosphorylation Promoter Regions Genetic Protein kinase A Protein Kinase Inhibitors Molecular Biology CAMK Cells Cultured ets-Domain Protein Elk-1 Mice Inbred ICR Gene knockdown Chemistry Kinase Cystathionine gamma-Lyase Cell biology Glucose Gene Expression Regulation Thapsigargin Mitogen-Activated Protein Kinases Calcium-Calmodulin-Dependent Protein Kinase Type 2 Protein Processing Post-Translational |
| Zdroj: | Molecular and Cellular Endocrinology. 350:31-38 |
| ISSN: | 0303-7207 |
| DOI: | 10.1016/j.mce.2011.11.016 |
| Popis: | Cystathionine γ-lyase (CSE) is one of the major enzymes for the production of hydrogen sulphide (H 2 S), a multifunctional gasotransmitter in the pancreatic β-cell. We examined the mechanisms by which glucose induces CSE expression in mouse pancreatic islets and the insulin-secreting cell line MIN6. CSE expression was increased by anti-diabetic sulphonylureas, and decreased by the ATP-sensitive K + -channel opener diazoxide and the voltage-dependent Ca 2+ channel blocker nitrendipine. Application of the synthetic inhibitors of protein kinases revealed the involvement of Ca 2+ /calmodulin-dependent protein kinase (CaMK) II and extracellular signal-regulated protein kinase (ERK) in glucose- and thapsigargin-induced CSE expression. The CaMK IIδ knockdown also suppressed CSE expression. Knockdown of the transcription factors Sp1 and Elk1, both of which can be phosphorylated by ERK, blunted CSE expression. By a reporter assay, we found Sp1 may directly and Elk1 may indirectly regulate CSE expression. These findings suggest Ca 2+ -dependent CSE expression may be mediated via protein phosphorylation of Sp1 and Elk1 in pancreatic β-cells. |
| Databáze: | OpenAIRE |
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