Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation.
Upregulation of mesencephalic astrocyte-derived neurotrophic factor in glial cells is associated with ischemia-induced glial activation.
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神经胶质细胞中中脑星形胶质细胞源性神经营养因子的上调与缺血诱导的神经胶质活化有关
DOI：
10.1186/1742-2094-9-254
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发表时间：
2012-11-23
影响因子：
9.3
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Shen Y;Sun A;Wang Y;Cha D;Wang H;Wang F;Feng L;Fang S;Shen Y
背景中脑星形胶质细胞源性神经营养因子（MANF）是一种20 kDa的分泌蛋白，最初来源于大鼠中脑1型星形胶质细胞细胞系。MANF与保守的多巴胺神经营养因子沿着属于一个新的进化保守的神经营养因子家族。近年来，越来越多的证据表明，二者在体内和体外对神经元的各种损伤均具有显著的保护作用。然而，MANF在不同类型的胶质细胞，特别是星形胶质细胞中的表达的特点，仍然不清楚。免疫荧光双标染色鉴定表达MANF的神经细胞类型。采用原代培养的胶质细胞检测胶质细胞对内质网应激刺激的反应。碘化丙啶染色用于确定死细胞。采用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blotting）检测MANF的mRNA和蛋白质水平。尽管其名称，MANF在正常脑组织中的胶质细胞（包括星形胶质细胞）中表达很差。然而，局灶性脑缺血时，MANF在胶质细胞中的表达上调，包括星形胶质细胞。在培养的原代神经胶质细胞中，这种表达也由几种内质网应激诱导剂和营养剥夺诱导。在这项研究中观察到的最有趣的现象是MANF在小胶质细胞中的表达模式。MANF的表达与小胶质细胞的形态和状态密切相关，并伴有BIP/Grp 78的上调。结论MANF在活化的胶质细胞中表达上调，可能参与了缺血性神经损伤的发生机制。
BackgroundMesencephalic astrocyte-derived neurotrophic factor (MANF), a 20 kDa secreted protein, was originally derived from a rat mesencephalic type-1 astrocyte cell line. MANF belongs to a novel evolutionally conserved family of neurotrophic factors along with conserved dopamine neurotrophic factor. In recent years, ever-increasing evidence has shown that both of them play a remarkable protective role against various injuries to neuronsin vivoorin vitro. However, the characteristics of MANF expression in the different types of glial cells, especially in astrocytes, remain unclear.MethodsThe model of focal cerebral ischemia was induced by rat middle cerebral artery occlusion. Double-labeled immunofluorescent staining was used to identify the types of neural cells expressing MANF. Primarily cultured glial cells were used to detect the response of glial cells to endoplasmic reticulum stress stimulation. Propidium iodide staining was used to determine dead cells. Reverse transcription PCR and western blotting were used to detect the levels of mRNA and proteins.ResultsWe found that MANF was predominantly expressed in neurons in both normal and ischemic cortex. Despite its name, MANF was poorly expressed in glial cells, including astrocytes, in normal brain tissue. However, the expression of MANF was upregulated in the glial cells under focal cerebral ischemia, including the astrocytes. This expression was also induced by several endoplasmic reticulum stress inducers and nutrient deprivation in cultured primary glial cells. The most interesting phenomenon observed in this study was the pattern of MANF expression in the microglia. The expression of MANF was closely associated with the morphology and state of microglia, accompanied by the upregulation of BIP/Grp78.ConclusionsThese results indicate that MANF expression was upregulated in the activated glial cells, which may contribute to the mechanism of ischemia-induced neural injury.
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DOI：
10.1111/j.1365-2990.1994.tb01173.x
发表时间：
1994-04-01
影响因子：
5
作者：
DELBIGIO, MR;BECKER, LE
通讯作者：
BECKER, LE
影响因子：
56.9
作者：
LIN, LFH;DOHERTY, DH;COLLINS, F
通讯作者：
COLLINS, F
影响因子：
3.5
作者：
Lindholm, Paivi;Peranen, Johan;Saarma, Mart
通讯作者：
Saarma, Mart
影响因子：
2.9
作者：
Jones, LL;Kreutzberg, GW;Raivich, G
通讯作者：
Raivich, G
影响因子：
6.2
作者：
Benavides, A;Pastor, D;Calvo, S
通讯作者：
Calvo, S