Regulation of gene expression of catecholamine biosynthetic enzymes in dopamine-beta-hydroxylase- and CRH-knockout mice exposed to stress.
Regulation of gene expression of catecholamine biosynthetic enzymes in dopamine-beta-hydroxylase- and CRH-knockout mice exposed to stress.
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在多巴胺β-羟化酶和CRH-敲除小鼠中暴露于应激的小鼠中，儿茶酚胺生物合成酶的基因表达调节。
DOI：
10.1196/annals.1410.033
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发表时间：
2008-12
影响因子：
5.2
通讯作者：
Kubovcakova L
中科院分区：
文献类型：
--
作者：
Kvetnanský R;Krizanova O;Tillinger A;Sabban EL;Thomas SA;Kubovcakova L
去甲肾上腺素缺乏小鼠具有多巴胺-β-羟化酶（DBH-KO）基因的破坏。促肾上腺皮质激素释放激素敲除小鼠（CRH-KO）HPA活性显著降低。本工作的目的是研究如何DBH和CRH的缺陷会影响酪氨酸羟化酶（TH），DBH，和苯乙醇胺N-甲基转移酶（PNMT）的基因表达和蛋白质水平在肾上腺髓质（AM）和星状神经节（SG）的控制和应激小鼠。在AM和SG中，单一固定显著增加野生型（WT）和CRH-KO小鼠中TH和DBH mRNA和蛋白水平。另一方面，在WT小鼠中观察到的PNMT mRNA和蛋白水平的应激触发的增加在CRH KO小鼠中不存在。DBH-KO小鼠对应激更敏感，但在试管中存活单个2小时束缚应激（RES）。在DBH-KO小鼠中未观察到WT中RES诱导的TH mRNA水平的增加。DNH-KO小鼠AM中PNMT mRNA和尤其是PNMT蛋白水平显著升高。在SG的DBH-KO小鼠TH mRNA水平不受影响，然而，PNMT基因表达高度升高。因此，DBH基因的破坏令人惊讶地阻断了AM中TH mRNA水平的应激诱导的升高，但增加了AM和SG中PNMT基因的表达。我们的数据表明，肾上腺素能信号是必需的应激诱导的TH mRNA的增加，这种信号抑制应激诱导的PNMT mRNA的增加。他们还证实HPA系统在PNMT基因表达的应激诱导调节中起着至关重要的作用。
Norepinephrine-deficient mice harbor a disruption of the gene for dopamine-β-hydroxylase (DBH-KO). Corticotropin-releasing hormone knockout mice (CRH-KO) have markedly reduced HPA activity. The aim of the present work was to study how deficiency of DBH and CRH would affect tyrosine hydroxylase (TH), DBH, and phenylethanolamine N-methyltransferase (PNMT) gene expression and protein levels in the adrenal medulla (AM) and stellate ganglia (SG) of control and stressed mice. Both in AM and SG, single immobilization significantly increased TH and DBH mRNA and protein levels both in wild-type (WT) and CRH-KO mice. On the other hand, the stress-triggered increase in the PNMT mRNA and protein levels seen in WT mice was absent in CRH KO mice. DBH-KO mice are more sensitive to stress but survive a single 2 h restraint stress in a tube (RES). The increase in TH mRNA levels induced by RES in WT was not observed in DBH-KO mice. PNMT mRNA and especially PNMT protein levels were significantly elevated in AM of DBH-KO mice. In SG of DBH-KO mice TH mRNA levels were not affected; however, PNMT gene expression was highly elevated. Thus, disruption of the DBH gene surprisingly blocks the stress-induced elevation of TH mRNA levels in AM but increases PNMT gene expression both in AM and SG. Our data indicate that adrenergic signaling is required for stress-induced increase in TH mRNA and that this signaling restrains stress-induced increase in PNMT mRNA. They also confirm that the HPA system plays a crucial role in the stress-induced regulation of PNMT gene expression.
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影响因子：
3.6
作者：
Tai, TC;Claycomb, R;Wong, DL
通讯作者：
Wong, DL
影响因子：
3.3
作者：
Kubovcakova, L;Krizanova, O;Kvetnansky, R
通讯作者：
Kvetnansky, R
影响因子：
3
作者：
Muglia, LJ;Jacobson, L;Majzoub, JA
通讯作者：
Majzoub, JA
影响因子：
4.8
作者：
Nankova, B;Kvetnansky, R;Sabban, EL
通讯作者：
Sabban, EL
影响因子：
15.9
作者：
Muglia, LJ;Jacobson, L;Majzoub, JA
通讯作者：
Majzoub, JA