Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.
Methamphetamine causes differential alterations in gene expression and patterns of histone acetylation/hypoacetylation in the rat nucleus accumbens.
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DOI：
10.1371/journal.pone.0034236
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Cadet JL
中科院分区：
文献类型：
--
作者：
Martin TA;Jayanthi S;McCoy MT;Brannock C;Ladenheim B;Garrett T;Lehrmann E;Becker KG;Cadet JL
甲基苯丙胺(冰毒)成瘾与多种神经精神症状有关。冰毒对大鼠伏隔核(NAC)基因表达和表观遗传修饰的影响知之甚少。我们的研究观察了无毒注射冰毒(20 mg/kg)对基因表达、组蛋白乙酰化以及组蛋白乙酰转移酶(HAT)ATF2和组蛋白脱乙酰酶(HDACs)HDAC1和HDAC2表达的影响。在注射冰毒后1、8、16和24小时进行的微阵列分析发现，冰毒诱导了先前与精神刺激剂的急性和长期影响有关的基因的表达变化，包括即刻早期基因和促肾上腺皮质激素释放因子(CRF)。相比之下，冰毒注射导致包括Npas4和CCK(CCK)在内的其他基因的表达随时间而下降。通路分析表明，表达改变的基因参与了行为表现、细胞间信号传递和基因表达调控。聚合酶链式反应分析证实c-fos、FosB、CRF、CCK和Npas4转录本的表达发生了变化。为了确定注射冰毒是否导致组蛋白标志物翻译后的变化，我们使用蛋白质印迹分析，并鉴定了冰毒介导的组蛋白H3在核亚组分中赖氨酸9(H3K9ac)和赖氨酸18(H3K18ac)乙酰化的减少。相比之下，冰毒注射引起乙酰化H4K5和H4K8的时间依赖性增加。组蛋白乙酰化的改变伴随着HDAC1蛋白表达的降低和HDAC2蛋白表达水平的升高。组蛋白乙酰转移酶ATF2在冰毒诱导下蛋白表达显著增加。这些结果表明，冰毒诱导的大鼠NAC整体基因表达的变化可能部分与冰毒诱导的组蛋白乙酰化的变化有关，继而是HAT和HDAC表达的变化。HATS和HDAC在冰毒诱导的基因表达中可能起到的因果作用需要进一步研究。
Methamphetamine (METH) addiction is associated with several neuropsychiatric symptoms. Little is known about the effects of METH on gene expression and epigenetic modifications in the rat nucleus accumbens (NAC). Our study investigated the effects of a non-toxic METH injection (20 mg/kg) on gene expression, histone acetylation, and the expression of the histone acetyltransferase (HAT), ATF2, and of the histone deacetylases (HDACs), HDAC1 and HDAC2, in that structure. Microarray analyses done at 1, 8, 16 and 24 hrs after the METH injection identified METH-induced changes in the expression of genes previously implicated in the acute and longterm effects of psychostimulants, including immediate early genes and corticotropin-releasing factor (Crf). In contrast, the METH injection caused time-dependent decreases in the expression of other genes including Npas4 and cholecystokinin (Cck). Pathway analyses showed that genes with altered expression participated in behavioral performance, cell-to-cell signaling, and regulation of gene expression. PCR analyses confirmed the changes in the expression of c-fos, fosB, Crf, Cck, and Npas4 transcripts. To determine if the METH injection caused post-translational changes in histone markers, we used western blot analyses and identified METH-mediated decreases in histone H3 acetylated at lysine 9 (H3K9ac) and lysine 18 (H3K18ac) in nuclear sub-fractions. In contrast, the METH injection caused time-dependent increases in acetylated H4K5 and H4K8. The changes in histone acetylation were accompanied by decreased expression of HDAC1 but increased expression of HDAC2 protein levels. The histone acetyltransferase, ATF2, showed significant METH-induced increased in protein expression. These results suggest that METH-induced alterations in global gene expression seen in rat NAC might be related, in part, to METH-induced changes in histone acetylation secondary to changes in HAT and HDAC expression. The causal role that HATs and HDACs might play in METH-induced gene expression needs to be investigated further.
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DOI：
10.1073/pnas.88.9.3720
发表时间：
1991-05-01
影响因子：
11.1
作者：
HAI, T;CURRAN, T
通讯作者：
CURRAN, T
影响因子：
4.2
作者：
Fukamauchi, F
通讯作者：
Fukamauchi, F
通过修复特定的组蛋白乙酰化，需要ATF2进行氨基酸调节的转录。
影响因子：
14.9
作者：
Bruhat, Alain;Cherasse, Yoan;Maurin, Anne-Catherine;Breitwieser, Wolfgang;Parry, Laurent;Deval, Christiane;Jones, Nic;Jousse, Celine;Fafournoux, Pierre
通讯作者：
Fafournoux, Pierre
影响因子：
3.7
作者：
Cadet, Jean Lud;Krasnova, Irina N.;Ladenheim, Bruce;Cai, Ning-Sheng;McCoy, Michael T.;Atianjoh, Fidelis E.
通讯作者：
Atianjoh, Fidelis E.
影响因子：
3.4
作者：
Hall, Darien A.;Stanis, Jessica J.;Gulley, Joshua M.
通讯作者：
Gulley, Joshua M.