Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions.
Activation of Erk and JNK MAPK pathways by acute swim stress in rat brain regions.
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DOI：
10.1186/1471-2202-5-36
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发表时间：
2004-09-20
期刊：
影响因子：
2.4
通讯作者：
Meller E
中科院分区：
文献类型：
--
作者：
Shen CP;Tsimberg Y;Salvadore C;Meller E
有丝分裂原活化蛋白激酶（MAPKs）已被证明参与广泛的细胞功能。一些MAPKs（如细胞外信号调节激酶，Erk1/2）的作用已被证明在对某些生理刺激的反应中，如缺血、内脏疼痛和电休克。我们最近证明，抑制应激激活Erk MAPK通路，但不激活c- jun - n末端激酶/应激激活蛋白激酶（JNK/SAPK）或p38MAPK，在几个大鼠大脑区域。在本研究中，我们研究了不同应激源（急性强迫游泳应激）对海马、新皮层、前额皮质、杏仁核和纹状体中这些MAPKs磷酸化(P)状态的影响。此外，我们还测定了上游MAPK激活因子及其各自的MAPK激酶（MAPKKs； P-MEK1/2、P-MKK4和P-MKK3/6）磷酸化状态的影响。最后，由于Erk通路可以激活c-AMP反应元件（CRE）结合（CREB）蛋白，并且最近有报道称游泳应激可增强CREB磷酸化，因此我们也研究了P-CREB的变化。单次15分钟的强迫游泳使新皮层、前额叶皮层和纹状体中的P-Erk2水平增加了2 - 3倍，但在海马体和杏仁核中没有。P-JNK水平（P-JNK1和/或P-JNK2/3）在所有脑区增加了约2 - 5倍，而P-p38MAPK水平基本保持不变。令人惊讶的是，磷酸化的MAPKKs， P-MEK1/2和P-MKK4（分别是Erk和JNK通路的激活因子）的水平在所有五个大脑区域中都增加了，并且更为显著（P-MEK1/2, 4.5至100倍；P-MKK4, 12至300倍）。与p38MAPK磷酸化缺乏强制游动相一致，其激活剂P-MKK3/6的水平似乎没有变化。P-CREB在除皮质（前额叶、新皮质）外的所有区域均升高。游泳应激特异性和显著增强了所有脑区MAPKKs P-MEK1/2和P-MKK4的磷酸化，而P-MKK3/6的磷酸化没有明显改变。奇怪的是，它们的同源底物（Erk和JNK）的磷酸化增加的程度要温和得多，并且在某些大脑区域没有改变。同样，Erk和CREB磷酸化之间也存在区域特异性差异。对这些发现的可能解释以及与约束应力效应的比较将被讨论。
The mitogen-activated protein kinases (MAPKs) have been shown to participate in a wide array of cellular functions. A role for some MAPKs (e.g., extracellular signal-regulated kinase, Erk1/2) has been documented in response to certain physiological stimuli, such as ischemia, visceral pain and electroconvulsive shock. We recently demonstrated that restraint stress activates the Erk MAPK pathway, but not c-Jun-N-terminal kinase/stress-activated protein kinase (JNK/SAPK) or p38MAPK, in several rat brain regions. In the present study, we investigated the effects of a different stressor, acute forced swim stress, on the phosphorylation (P) state of these MAPKs in the hippocampus, neocortex, prefrontal cortex, amygdala and striatum. In addition, effects on the phosphorylation state of the upstream activators of the MAPKs, their respective MAPK kinases (MAPKKs; P-MEK1/2, P-MKK4 and P-MKK3/6), were determined. Finally, because the Erk pathway can activate c-AMP response element (CRE) binding (CREB) protein, and swim stress has recently been reported to enhance CREB phosphorylation, changes in P-CREB were also examined. A single 15 min session of forced swimming increased P-Erk2 levels 2–3-fold in the neocortex, prefrontal cortex and striatum, but not in the hippocampus or amygdala. P-JNK levels (P-JNK1 and/or P-JNK2/3) were increased in all brain regions about 2–5-fold, whereas P-p38MAPK levels remained essentially unchanged. Surprisingly, levels of the phosphorylated MAPKKs, P-MEK1/2 and P-MKK4 (activators of the Erk and JNK pathways, respectively) were increased in all five brain regions, and much more dramatically (P-MEK1/2, 4.5 to > 100-fold; P-MKK4, 12 to ~300-fold). Consistent with the lack of forced swim on phosphorylation of p38MAPK, there appeared to be no change in levels of its activator, P-MKK3/6. P-CREB was increased in all but cortical (prefrontal, neocortex) areas. Swim stress specifically and markedly enhanced the phosphorylation of the MAPKKs P-MEK1/2 and P-MKK4 in all brain regions tested without apparent alteration in the phosphorylation of P-MKK3/6. Curiously, phosphorylation of their cognate substrates (Erk and JNK) was increased to a much more modest extent, and in some brain regions was not altered. Similarly, there was a region-specific discrepancy between Erk and CREB phosphorylation. Possible explanations for these findings and comparison with the effects of restraint stress will be discussed.
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DOI：
10.1073/pnas.96.22.12866
发表时间：
1999-10-26
影响因子：
11.1
作者：
Alessandrini, A;Namura, S;Bonventre, JV
通讯作者：
Bonventre, JV
影响因子：
4.7
作者：
Dudman, JT;Eaton, ME;Konradi, C
通讯作者：
Konradi, C
影响因子：
13.5
作者：
Graves, JD;Krebs, EG
通讯作者：
Krebs, EG
DOI：
10.1016/s0169-328x(99)00329-0
发表时间：
2000-03-10
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Cammarota, M;Bevilaqua, LRM;Medina, JH
通讯作者：
Medina, JH
影响因子：
2.9
作者：
CLEMENT, HW;SCHAFER, F;WESEMANN, W
通讯作者：
WESEMANN, W