期刊
MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 350, 期 1, 页码 31-38出版社
ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2011.11.016
关键词
Hydrogen sulphide; Pancreatic islets; MAPK; CaMK II; Cystathionine gamma-lyase
资金
- KAKENHI from Japan Society Promotion of Science [21591146, 22790255]
- Oita University
- Oita Broadcasting System Cultural Foundation
- Venture Business Laboratory, Oita University
- Grants-in-Aid for Scientific Research [23791039, 21591146, 22790255, 22590292, 23659089, 23500451] Funding Source: KAKEN
Cystathionine gamma-lyase (CSE) is one of the major enzymes for the production of hydrogen sulphide (H2S), a multifunctional gasotransmitter in the pancreatic beta-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 Ca2+ channel blocker nitrendipine. Application of the synthetic inhibitors of protein kinases revealed the involvement of Ca2+/calmodulin-dependent protein kinase (CaMK) II and extracellular signal-regulated protein kinase (ERK) in glucose- and thapsigargin-induced CSE expression. The CaMK II delta 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 Ca2+-dependent CSE expression may be mediated via protein phosphorylation of Sp1 and Elk1 in pancreatic beta-cells. (C) 2011 Elsevier Ireland Ltd. All rights reserved.
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