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地佐环平不会改变大鼠和细胞培养物中的基因表达。

Dizocilpine Does Not Alter Gene Expression in Rats and in Cell Cultures.

作者信息

Matiiv Anton B, Rogoza Tatyana M, Razgovorova Irina A, Zhdanova Maria I, Trubitsina Nina P, Bezgina Mariya D, Isaeva Irina G, Markov Alexander G, Zhouravleva Galina A, Bondarev Stanislav A

机构信息

Department of Genetics and Biotechnology, St. Petersburg State University, 7/9 Universitetskaya emb., St. Petersburg 199034, Russia.

St. Petersburg Branch of the N.I. Vavilov Institute of General Genetics, St. Petersburg 199034, Russia.

出版信息

Int J Mol Sci. 2025 Jun 1;26(11):5329. doi: 10.3390/ijms26115329.

DOI:10.3390/ijms26115329
PMID:40508138
Abstract

The gene encodes the nitric oxide synthase 1 adaptor protein (NOS1AP), which binds to neuronal nitric oxide synthase (nNOS) and regulates nitric oxide (NO) production by dissociating nNOS from NMDA receptors (NMDARs). Notably, NOS1AP expression is upregulated upon NMDAR activation; however, there is no available data regarding its production under the receptor inhibition. The gene is also 1 among more than 1000 genes that are presumed to be associated with the development of schizophrenia. Various animal models of this disorder have been developed, some of which are based on the use of NMDAR antagonists such as dizocilpine (MK-801). In this study, we investigated the expression and production of NOS1AP in rats injected with a low dose of dizocilpine (0.1 mg/kg), as well as in SH-SY5Y and HEK293T cell lines treated with varying concentrations of the same compound (10-200 µM). According to our results, neither the expression of the gene nor the production of NOS1AP protein was affected by dizocilpine treatment.

摘要

该基因编码一氧化氮合酶1衔接蛋白(NOS1AP),它与神经元型一氧化氮合酶(nNOS)结合,并通过使nNOS与N-甲基-D-天冬氨酸受体(NMDARs)解离来调节一氧化氮(NO)的产生。值得注意的是,NMDAR激活后NOS1AP表达上调;然而,关于其在受体抑制情况下的产生情况尚无可用数据。该基因也是推测与精神分裂症发生相关的1000多个基因之一。已经开发了多种该疾病的动物模型,其中一些基于使用NMDAR拮抗剂,如地卓西平(MK-801)。在本研究中,我们研究了注射低剂量地卓西平(0.1 mg/kg)的大鼠以及用不同浓度的同一化合物(10 - 200 μM)处理的SH-SY5Y和HEK293T细胞系中NOS1AP的表达和产生情况。根据我们的结果,地卓西平处理既不影响该基因的表达,也不影响NOS1AP蛋白的产生。

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本文引用的文献

1
Disrupting the nNOS/NOS1AP interaction in the medial prefrontal cortex impairs social recognition and spatial working memory in mice.破坏内侧前额叶皮质中的nNOS/NOS1AP相互作用会损害小鼠的社会识别和空间工作记忆。
Eur Neuropsychopharmacol. 2023 Feb;67:66-79. doi: 10.1016/j.euroneuro.2022.11.006. Epub 2022 Dec 10.
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Glutamatergic dysfunction in Schizophrenia.精神分裂症中的谷氨酸能功能障碍。
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3
NOS1AP Interacts with α-Synuclein and Aggregates in Yeast and Mammalian Cells.
NOS1AP 与α-突触核蛋白在酵母和哺乳动物细胞中相互作用并聚集。
Int J Mol Sci. 2022 Aug 14;23(16):9102. doi: 10.3390/ijms23169102.
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Altered expression levels of miR-144-3p and ATP1B2 are associated with schizophrenia.miR-144-3p 和 ATP1B2 的表达水平改变与精神分裂症有关。
World J Biol Psychiatry. 2022 Nov;23(9):666-676. doi: 10.1080/15622975.2021.2022757. Epub 2022 Jan 17.
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Recessive variants impair actin remodeling and cause glomerulopathy in humans and mice.隐性变异会损害肌动蛋白重塑,并导致人类和小鼠的肾小球病。
Sci Adv. 2021 Jan 1;7(1). doi: 10.1126/sciadv.abe1386. Print 2021 Jan.
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SynGAP splice variants display heterogeneous spatio-temporal expression and subcellular distribution in the developing mammalian brain.SynGAP 剪接变异体在发育中的哺乳动物大脑中表现出异质的时空表达和亚细胞分布。
J Neurochem. 2020 Sep;154(6):618-634. doi: 10.1111/jnc.14988. Epub 2020 Mar 10.
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In Vitro and In Vivo Models for the Investigation of Potential Drugs Against Schizophrenia.用于研究抗精神分裂症潜在药物的体外和体内模型。
Biomolecules. 2020 Jan 19;10(1):160. doi: 10.3390/biom10010160.
8
The origin of NMDA receptor hypofunction in schizophrenia.精神分裂症中 NMDA 受体功能低下的起源。
Pharmacol Ther. 2020 Jan;205:107426. doi: 10.1016/j.pharmthera.2019.107426. Epub 2019 Oct 16.
9
Famotidine has a neuroprotective effect on MK-801 induced toxicity via the Akt/GSK-3β/β-catenin signaling pathway in the SH-SY5Y cell line.法莫替丁通过 Akt/GSK-3β/β-连环蛋白信号通路对 MK-801 诱导的 SH-SY5Y 细胞毒性具有神经保护作用。
Chem Biol Interact. 2019 Dec 1;314:108823. doi: 10.1016/j.cbi.2019.108823. Epub 2019 Sep 26.
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Neurochem Res. 2019 Nov;44(11):2536-2545. doi: 10.1007/s11064-019-02873-7. Epub 2019 Sep 16.