磷酸二酯酶2负向调节大鼠嗜铬细胞瘤PC12细胞中腺苷诱导的酪氨酸羟化酶基因转录。

Phosphodiesterase 2 negatively regulates adenosine-induced transcription of the tyrosine hydroxylase gene in PC12 rat pheochromocytoma cells.

作者信息

Makuch Edyta, Kuropatwa Marianna, Kurowska Ewa, Ciekot Jaroslaw, Klopotowska Dagmara, Matuszyk Janusz

机构信息

Laboratory of Signaling Proteins, Ludwik Hirszfeld Institute of Immunology and Experimental Therapy, Polish Academy of Sciences, Weigla 12, 53-114 Wroclaw, Poland.

出版信息

Mol Cell Endocrinol. 2014 Jul 5;392(1-2):51-9. doi: 10.1016/j.mce.2014.05.001. Epub 2014 May 15.

DOI:10.1016/j.mce.2014.05.001

PMID:24837549

Abstract

Adenosine induces expression of the tyrosine hydroxylase (TH) gene in PC12 cells. However, it is suggested that atrial natriuretic peptide (ANP) inhibits expression of this gene. Using real-time PCR and luciferase reporter assays we found that ANP significantly decreases the adenosine-induced transcription of the TH gene. Results of measurements of cyclic nucleotide concentrations indicated that ANP-induced accumulation of cGMP inhibits the adenosine-induced increase in cAMP level. Using selective phosphodiesterase 2 (PDE2) inhibitors and a synthetic cGMP analog activating PDE2, we found that PDE2 is involved in coupling the ANP-triggered signal to the cAMP metabolism. We have established that ANP-induced elevated levels of cGMP as well as cGMP analog stimulate hydrolytic activity of PDE2, leading to inhibition of adenosine-induced transcription of the TH gene. We conclude that ANP mediates negative regulation of TH gene expression via stimulation of PDE2-dependent cAMP breakdown in PC12 cells.

摘要

腺苷可诱导PC12细胞中酪氨酸羟化酶（TH）基因的表达。然而，有研究表明心房利钠肽（ANP）会抑制该基因的表达。通过实时定量PCR和荧光素酶报告基因检测，我们发现ANP能显著降低腺苷诱导的TH基因转录。环核苷酸浓度的测量结果表明，ANP诱导的cGMP积累会抑制腺苷诱导的cAMP水平升高。使用选择性磷酸二酯酶2（PDE2）抑制剂和一种激活PDE2的合成cGMP类似物，我们发现PDE2参与了将ANP触发的信号与cAMP代谢相偶联的过程。我们已经证实，ANP诱导的cGMP水平升高以及cGMP类似物会刺激PDE2的水解活性，从而抑制腺苷诱导的TH基因转录。我们得出结论，ANP通过刺激PC12细胞中依赖PDE2的cAMP降解来介导TH基因表达的负调控。