Vitamin A bio-modulates apoptosis via the mitochondrial pathway after hypoxic-ischemic brain damage.
Vitamin A bio-modulates apoptosis via the mitochondrial pathway after hypoxic-ischemic brain damage.
复制标题
缺氧缺血性脑损伤后维生素 A 通过线粒体途径生物调节细胞凋亡
DOI：
10.1186/s13041-018-0360-0
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发表时间：
2018-03-13
期刊：
影响因子：
3.6
通讯作者：
Li T
中科院分区：
文献类型：
--
作者：
Jiang W;Guo M;Gong M;Chen L;Bi Y;Zhang Y;Shi Y;Qu P;Liu Y;Chen J;Li T
我们之前的研究表明，维生素A缺乏症（VAD）可以通过损害海马来损害大鼠的出生后认知功能。本研究在体内和体外观察维甲酸（RA）对缺氧缺血性损伤诱导的细胞凋亡的影响，并探讨RA抗凋亡神经保护作用可能涉及的信号通路。采用流式细胞术、免疫荧光染色和行为学实验评价RA的神经保护作用和抗凋亡作用。采用western blotting和real-time PCR分别检测RARα、PI3K、Akt、Bad、caspase-3、caspase-8、Bcl-2、Bax、Bid蛋白和mRNA水平。与维生素A正常组（VAN）和维生素A补充组（VAS）相比，VAD组在学习和空间记忆方面存在障碍。此外，我们发现VAN组海马细胞凋亡明显弱于VAD组。与VAD组相比，VAN组体内RARα和PI3K mRNA和蛋白水平升高，磷酸化Akt/Bad水平上调。在体外，过低或过高的RA信号均可促进细胞凋亡。此外，对细胞凋亡的影响还涉及线粒体膜电位（MMP）。这些数据支持了以下观点：缺氧缺血性脑损伤（HIBD）后持续的VAD抑制RARα， RARα下调PI3K/Akt/Bad和Bcl-2/Bax通路，上调caspase-8/Bid通路，从而影响MMP，最终导致青少年学习和空间记忆缺陷。这表明HIBD的临床干预应包括适当剂量的VA。
Our previous studies demonstrated that vitamin A deficiency (VAD) can impair the postnatal cognitive function of rats by damaging the hippocampus. The present study examined the effects of retinoic acid (RA) on apoptosis induced by hypoxic-ischemic damage in vivo and in vitro,and investigated the possible signaling pathway involved in the neuroprotective anti-apoptotic effects of RA. Flow cytometry, immunofluorescence staining and behavioral tests were used to evaluate the neuroprotective and anti-apoptotic effects of RA. The protein and mRNA levels of RARα, PI3K, Akt, Bad, caspase-3, caspase-8, Bcl-2, Bax, and Bid were measured with western blotting and real-time PCR, respectively. We found impairments in learning and spatial memory in VAD group compared with vitamin A normal (VAN) and vitamin A supplemented (VAS) group. Additionally, we showed that hippocampal apoptosis was weaker in the VAN group than that in VAD group. Relative to the VAD group, the VAN group also had increased mRNA and protein levels of RARα and PI3K, and upregulated phosphorylated Akt/Bad levels in vivo. In vitro, excessively low or high RA signaling promoted apoptosis. Furthermore, the effects on apoptosis involved the mitochondrial membrane potential (MMP). These data support the idea that sustained VAD following hypoxic-ischemic brain damage (HIBD) inhibits RARα, which downregulates the PI3K/Akt/Bad and Bcl-2/Bax pathways and upregulates the caspase-8/Bid pathway to influence the MMP, ultimately producing deficits in learning and spatial memory in adolescence. This suggests that clinical interventions for HIBD should include suitable doses of VA.
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黄芩苷通过减少海马细胞凋亡提高整体缺血/再灌注大鼠的空间学习能力
影响因子：
2.9
作者：
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DOI：
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发表时间：
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影响因子：
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作者：
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通讯作者：
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3.5
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通讯作者：
Evans T
DOI：
10.1073/pnas.191369798
发表时间：
2001-09-25
影响因子：
11.1
作者：
Misner, DL;Jacobs, S;Evans, RM
通讯作者：
Evans, RM