Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.
Cell type-specific dependency on the PI3K/Akt signaling pathway for the endogenous Epo and VEGF induction by baicalein in neurons versus astrocytes.
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细胞类型特异性依赖性对PI3K/AKT信号传导途径，用于神经元与星形胶质细胞中的黄胶蛋白的内源性EPO和VEGF诱导。
DOI：
10.1371/journal.pone.0069019
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Lee YH
中科院分区：
文献类型：
--
作者：
Sun YY;Lin SH;Lin HC;Hung CC;Wang CY;Lin YC;Hung KS;Lien CC;Kuan CY;Lee YH
黄芩素的神经保护作用通常归因于抑制12/15-脂氧合酶（12/15-LOX）和抑制氧化应激，但最近的研究表明黄芩素还通过抑制脯氨酰水解酶2（PHD 2）和激活磷脂酰肌醇-3激酶（PI 3 K）/Akt信号通路激活缺氧诱导因子-α（HIF 1 α）。然而，促存活细胞因子促红细胞生成素（Epo）和血管内皮生长因子（VEGF），HIF 1 α的两个转录靶点，在黄芩苷介导的神经元和星形胶质细胞的神经保护中的意义和调节仍然未知。在这里，我们调查的因果关系PI 3 K/Akt信号通路和Epo/VEGF表达黄芩苷介导的神经保护原代大鼠皮层神经元和星形胶质细胞。结果表明黄芩素以HIF 1 α和PI 3 K/Akt依赖的方式诱导神经元Epo和VEGF表达。黄芩素还以PI 3 K和Epo/VEGF依赖的方式保护神经元免受兴奋性毒性，而不影响神经元的兴奋性。相反，至少需要10倍高浓度的黄芩素来诱导星形胶质细胞中Epo/VEGF产生和PI 3 K/Akt活性以保护神经元。此外，只有黄芩苷诱导的星形胶质细胞VEGF表达需要HIF 1 α，而Epo表达不需要HIF 1 α，而PI 3 K/Akt信号在黄芩苷诱导的星形胶质细胞Epo/VEGF表达中几乎没有作用。这些结果表明黄芩素介导的Epo/VEGF在神经元和星形胶质细胞中产生神经保护作用的不同机制，并为黄芩素在体内治疗脑损伤的机制和潜力提供了新的见解。
The neuroprotective effect of baicalein is generally attributed to inhibition of 12/15-lipoxygenase (12/15-LOX) and suppression of oxidative stress, but recent studies showed that baicalein also activates hypoxia-inducible factor-α (HIF1α) through inhibition of prolyl hydrolase 2 (PHD2) and activation of the phosphatidylinositide-3 kinase (PI3K)/Akt signaling pathway. Yet, the significance and regulation of prosurvival cytokines erythropoietin (Epo) and vascular endothelial growth factor (VEGF), two transcriptional targets of HIF1α, in baicalein-mediated neuroprotection in neurons and astrocytes remains unknown. Here we investigated the causal relationship between the PI3K/Akt signaling pathway and Epo/VEGF expression in baicalein-mediated neuroprotection in primary rat cortical neurons and astrocytes. Our results show that baicalein induced Epo and VEGF expression in a HIF1α- and PI3K/Akt-dependent manner in neurons. Baicalein also protected neurons against excitotoxicity in a PI3K- and Epo/VEGF-dependent manner without affecting neuronal excitability. In contrast, at least a 10-fold higher concentration of baicalein was needed to induce Epo/VEGF production and PI3K/Akt activity in astrocytes for protection of neurons. Moreover, only baicalein-induced astrocytic VEGF, but not Epo expression requires HIF1α, while PI3K/Akt signaling had little role in baicalein-induced astrocytic Epo/VEGF expression. These results suggest distinct mechanisms of baicalein-mediated Epo/VEGF production in neurons and astrocytes for neuroprotection, and provide new insights into the mechanisms and potential of baicalein in treating brain injury in vivo.
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影响因子：
3.6
作者：
Cho, Hyunju;Lee, Ho-Youl;Yang, Eun Gyeong
通讯作者：
Yang, Eun Gyeong
影响因子：
3.7
作者：
Mowat FM;Luhmann UF;Smith AJ;Lange C;Duran Y;Harten S;Shukla D;Maxwell PH;Ali RR;Bainbridge JW
通讯作者：
Bainbridge JW
影响因子：
2.9
作者：
Lee, HH;Yang, LL;Lee, YH
通讯作者：
Lee, YH
影响因子：
2
作者：
Kong, Dexin;Yamazaki, Kanami;Yamori, Takao
通讯作者：
Yamori, Takao
影响因子：
5.3
作者：
Chavez, Juan C.;Baranova, Oxana;Pichiule, Paola
通讯作者：
Pichiule, Paola