Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression.
Odorant Stimulation Promotes Survival of Rodent Olfactory Receptor Neurons via PI3K/Akt Activation and Bcl-2 Expression.
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DOI：
10.14348/molcells.2015.0038
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发表时间：
2015-06
影响因子：
3.8
通讯作者：
Moon C
中科院分区：
文献类型：
--
作者：
Kim SY;Yoo SJ;Ronnett GV;Kim EK;Moon C
嗅觉刺激激活多个信号级联，以介导活性驱动的基因表达变化，促进神经元的存活。迄今为止，参与活动依赖性嗅觉神经元存活的机制尚未完全阐明。在本研究中，我们观察到嗅觉刺激引起神经元激活，促进磷脂酰肌醇3′-激酶（PI 3 K）/Akt通路的激活和Bcl-2的表达，这些通路负责嗅觉受体神经元（ORN）的存活。我们证明，Bcl-2的表达增加气味刺激后，在体内和体外。我们还表明，气味刺激激活Akt，Akt的激活被完全阻断与PI 3 K抑制剂（LY 294002）和Akt 1小干扰RNA孵育。此外，阻断PI 3 K/Akt通路减少了气味诱导的Bcl-2表达，以及对气味诱导的ORN存活的影响。气味刺激后Akt 1的激活和Bcl-2的表达之间存在时间差异。阻断PI 3 K/Akt通路在Bcl-2表达增加之前的时间范围内不影响ORN存活，这意味着这两个事件，PI 3 K通路的激活和Bcl-2诱导，与促进翻译后ORN存活紧密相关。总的来说，我们的研究结果表明，嗅觉活动激活PI 3 K/Akt，诱导Bcl-2，并促进长期ORN的生存。
Olfactory stimulation activates multiple signaling cascades in order to mediate activity-driven changes in gene expression that promote neuronal survival. To date, the mechanisms involved in activity-dependent olfactory neuronal survival have yet to be fully elucidated. In the current study, we observed that olfactory sensory stimulation, which caused neuronal activation, promoted activation of the phosphatidylinositol 3′-kinase (PI3K)/Akt pathway and the expression of Bcl-2, which were responsible for olfactory receptor neuron (ORN) survival. We demonstrated that Bcl-2 expression increased after odorant stimulation both in vivo and in vitro. We also showed that odorant stimulation activated Akt, and that Akt activation was completely blocked by incubation with both a PI3K inhibitor (LY294002) and Akt1 small interfering RNA. Moreover, blocking the PI3K/Akt pathway diminished the odorant-induced Bcl-2 expression, as well as the effects on odorant-induced ORN survival. A temporal difference was noted between the activation of Akt1 and the expression of Bcl-2 following odorant stimulation. Blocking the PI3K/Akt pathway did not affect ORN survival in the time range prior to the increase in Bcl-2 expression, implying that these two events, activation of the PI3K pathway and Bcl-2 induction, were tightly connected to promote post-translational ORN survival. Collectively, our results indicated that olfactory activity activated PI3K/Akt, induced Bcl-2, and promoted long term ORN survival as a result.
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DOI：
10.1073/pnas.76.9.4350
发表时间：
1979-01-01
影响因子：
11.1
作者：
TOWBIN, H;STAEHELIN, T;GORDON, J
通讯作者：
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影响因子：
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作者：
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Ache, Barry W.
影响因子：
4.5
作者：
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通讯作者：
Stern, Michael