Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell

Shigeki Taniguchi; Toshihide Kimura; Tatsuhito Umeki; Yuka Kimura; Hideo Kimura; Isao Ishii; Norimichi Itoh; Yasuhito Naito; Hideyuki Yamamoto; Ichiro Niki

doi:10.1016/j.mce.2011.11.016

Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine γ-lyase in the pancreatic β-cell

Mol Cell Endocrinol. 2012 Mar 5;350(1):31-8. doi: 10.1016/j.mce.2011.11.016. Epub 2011 Nov 25.

Authors

Shigeki Taniguchi¹, Toshihide Kimura, Tatsuhito Umeki, Yuka Kimura, Hideo Kimura, Isao Ishii, Norimichi Itoh, Yasuhito Naito, Hideyuki Yamamoto, Ichiro Niki

Affiliation

¹ Department of Pharmacology, Oita University, 1-1 Idaigaoka, Hasama, Oita 879-5593, Japan.

PMID: 22133746
DOI: 10.1016/j.mce.2011.11.016

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Calcium Signaling
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / antagonists & inhibitors
Calcium-Calmodulin-Dependent Protein Kinase Type 2 / metabolism
Cells, Cultured
Cystathionine beta-Synthase / genetics
Cystathionine beta-Synthase / metabolism
Cystathionine gamma-Lyase / genetics*
Cystathionine gamma-Lyase / metabolism
Gene Expression Regulation
Gene Expression*
Glucose / pharmacology
Glucose / physiology
Glyburide / pharmacology
Hydrogen Sulfide / metabolism*
Hypoglycemic Agents / pharmacology
Insulin / metabolism
Insulin Secretion
Insulin-Secreting Cells / drug effects
Insulin-Secreting Cells / enzymology*
Insulin-Secreting Cells / metabolism
Male
Mice
Mice, Inbred ICR
Mitogen-Activated Protein Kinases / antagonists & inhibitors
Mitogen-Activated Protein Kinases / metabolism
Phosphorylation
Promoter Regions, Genetic
Protein Kinase Inhibitors / pharmacology
Protein Processing, Post-Translational*
Sp1 Transcription Factor / metabolism
Thapsigargin / pharmacology
Tolbutamide / pharmacology
ets-Domain Protein Elk-1 / metabolism

Substances

Elk1 protein, mouse
Hypoglycemic Agents
Insulin
Protein Kinase Inhibitors
Sp1 Transcription Factor
ets-Domain Protein Elk-1
Thapsigargin
Tolbutamide
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Mitogen-Activated Protein Kinases
Cystathionine beta-Synthase
Cystathionine gamma-Lyase
Glucose
Glyburide
Hydrogen Sulfide