Protein phosphorylation involved in the gene expression of the hydrogen sulphide producing enzyme cystathionine ¦Ã-lyase in the pancreatic ¦Â-cell

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• 作者：Shigeki Taniguchi^a ; Toshihide Kimura^a ; Tatsuhito Umeki^a ; Yuka Kimura^b ; Hideo Kimura^b ; Isao Ishii^c ; Norimichi Itoh^d ; Yasuhito Naito^e ; Hideyuki Yamamoto^f ; Ichiro Niki^a ; ^{niki@oita-u.ac.jp}
• 关键词：CaMK ; Ca2+/calmodulin-dependent protein kinase ; CAT ; cysteine aminotransferase ; CBS ; cystathionine ¦Â-synthase ; CO ; carbon monoxide ; CSE ; cystathionine ¦Ã-lyase ; Elk1 ; Ets-like protein-1 ; ER ; endoplasmic reticulum ; ERK ; extracellular signal-regulated prot
• 刊名：Molecular and Cellular Endocrinology
• 出版年：2012
• 出版时间：5 March 2012
• 年：2012
• 卷：350
• 期：1
• 页码：31-38
• 全文大小：875 K

文摘

Cystathionine ¦Ã-lyase (CSE) is one of the major enzymes for the production of hydrogen sulphide (H₂S), a multifunctional gasotransmitter in the pancreatic ¦Â-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¦Ä 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 ¦Â-cells.