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3-(2-羧基哌嗪-4-基)丙基-1-膦酸的抗抑郁作用是由组蛋白去乙酰化酶5的磷酸化介导的。

The antidepressant action of 3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid is mediated by phosphorylation of histone deacetylase 5.

作者信息

Park Min Hyeop, Choi Miyeon, Kim Yong-Seok, Son Hyeon

机构信息

Department of Biomedical Sciences, Graduate School of Biomedical Science and Engineering, Seoul 04763, Korea.

Department of Biochemistry and Molecular Biology, College of Medicine, Hanyang University, Seoul 04763, Korea.

出版信息

Korean J Physiol Pharmacol. 2018 Mar;22(2):155-162. doi: 10.4196/kjpp.2018.22.2.155. Epub 2018 Feb 23.

DOI:10.4196/kjpp.2018.22.2.155
PMID:29520168
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5840074/
Abstract

3-(2-Carboxypiperazin-4-yl)propyl-1-phosphonic acid (CPP), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, produces rapid antidepressant-like effects in animal models of depression. However, the molecular mechanisms underlying these behavioral actions remain unknown. Here, we demonstrate that CPP rapidly stimulates histone deacetylase (HDAC) 5 phosphorylation and nuclear export in rat hippocampal neurons. These effects are accompanied by calcium/calmodulin kinase II (CaMKII) and protein kinase D (PKD) phosphorylation. Behavioral experiments revealed that viral-mediated hippocampal knockdown of HDAC5 blocked the antidepressant effects of CPP in stressed animals. Taken together, our results imply that CPP acts via HDAC5 and suggest that HDAC5 is a common regulator contributing to the antidepressant actions of NMDA receptor antagonists such as CPP.

摘要

3-(2-羧基哌嗪-4-基)丙基-1-膦酸（CPP）是一种竞争性N-甲基-D-天冬氨酸（NMDA）受体拮抗剂，在抑郁症动物模型中可产生快速的抗抑郁样效应。然而，这些行为作用背后的分子机制仍不清楚。在此，我们证明CPP可快速刺激大鼠海马神经元中组蛋白脱乙酰酶（HDAC）5的磷酸化和核输出。这些效应伴随着钙/钙调蛋白激酶II（CaMKII）和蛋白激酶D（PKD）的磷酸化。行为实验表明，病毒介导的海马HDAC5基因敲低可阻断CPP对应激动物的抗抑郁作用。综上所述，我们的结果表明CPP通过HDAC5发挥作用，并提示HDAC5是促成NMDA受体拮抗剂（如CPP）抗抑郁作用的共同调节因子。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/1edca753a793/kjpp-22-155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/b68da6646faf/kjpp-22-155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/846c925a1479/kjpp-22-155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/a37711b49fb7/kjpp-22-155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/1edca753a793/kjpp-22-155-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/b68da6646faf/kjpp-22-155-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/846c925a1479/kjpp-22-155-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/a37711b49fb7/kjpp-22-155-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b905/5840074/1edca753a793/kjpp-22-155-g004.jpg

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本文引用的文献

1
NMDAR inhibition-independent antidepressant actions of ketamine metabolites.氯胺酮代谢物的非NMDAR抑制依赖性抗抑郁作用。
Nature. 2016 May 26;533(7604):481-6. doi: 10.1038/nature17998. Epub 2016 May 4.
2
Ketamine produces antidepressant-like effects through phosphorylation-dependent nuclear export of histone deacetylase 5 (HDAC5) in rats.氯胺酮通过依赖磷酸化的组蛋白脱乙酰基酶5（HDAC5）核输出在大鼠中产生抗抑郁样效应。
Proc Natl Acad Sci U S A. 2015 Dec 22;112(51):15755-60. doi: 10.1073/pnas.1513913112. Epub 2015 Dec 8.
3
Expression of class II histone deacetylases in two mouse models of temporal lobe epilepsy.
II类组蛋白去乙酰化酶在两种颞叶癫痫小鼠模型中的表达
J Neurochem. 2016 Feb;136(4):717-730. doi: 10.1111/jnc.13440. Epub 2015 Dec 28.
4
Hippocampal neuroplasticity in major depressive disorder.重度抑郁症中的海马神经可塑性。
Neuroscience. 2015 Nov 19;309:200-13. doi: 10.1016/j.neuroscience.2015.04.047. Epub 2015 Apr 28.
5
Conceptual confluence: the kynurenine pathway as a common target for ketamine and the convergence of the inflammation and glutamate hypotheses of depression.概念融合：犬尿氨酸途径作为氯胺酮的共同靶点以及抑郁症炎症假说与谷氨酸假说的趋同
Neuropsychopharmacology. 2013 Aug;38(9):1607-8. doi: 10.1038/npp.2013.140.
6
Synaptic dysfunction in depression: potential therapeutic targets.抑郁症中的突触功能障碍：潜在的治疗靶点。
Science. 2012 Oct 5;338(6103):68-72. doi: 10.1126/science.1222939.
7
Protein kinase D-HDAC5 signaling regulates erythropoiesis and contributes to erythropoietin cross-talk with GATA1.蛋白激酶 D-HDAC5 信号通路调控红细胞生成，促进了红细胞生成素与 GATA1 的相互作用。
Blood. 2012 Nov 15;120(20):4219-28. doi: 10.1182/blood-2011-10-387050. Epub 2012 Sep 14.
8
Chronic ketamine administration modulates midbrain dopamine system in mice.慢性氯胺酮给药调节小鼠中脑多巴胺系统。
PLoS One. 2012;7(8):e43947. doi: 10.1371/journal.pone.0043947. Epub 2012 Aug 24.
9
Decreased expression of synapse-related genes and loss of synapses in major depressive disorder.突触相关基因表达减少和突触丢失在重度抑郁症中的作用。
Nat Med. 2012 Sep;18(9):1413-7. doi: 10.1038/nm.2886.
10
Epigenetics of the depressed brain: role of histone acetylation and methylation.抑郁大脑的表观遗传学：组蛋白乙酰化和甲基化的作用。
Neuropsychopharmacology. 2013 Jan;38(1):124-37. doi: 10.1038/npp.2012.73. Epub 2012 Jun 13.