Protection of neurons from high glucose-induced injury by deletion of MAD2B.
Protection of neurons from high glucose-induced injury by deletion of MAD2B.
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通过删除 MAD2B 保护神经元免受高糖诱导的损伤
DOI：
10.1111/jcmm.12229
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发表时间：
2014-05
影响因子：
5.3
通讯作者：
Zhang C
中科院分区：
文献类型：
--
作者：
Meng X;Wang X;Tian X;Yang Z;Li M;Zhang C
糖尿病脑病可能导致糖尿病患者的认知缺陷并降低生活质量。研究表明，持续性高血糖与神经元凋亡直接相关，而神经元凋亡与糖尿病脑病有关。后期促进复合物（APC）对有丝分裂后神经元的存活至关重要。在我们之前的研究中，我们发现有丝分裂阻滞缺陷蛋白MAD 2B（APC抑制剂之一）在中枢神经系统的神经元中表达。然而，MAD2B是否参与高血糖诱导的细胞凋亡，从而参与糖尿病脑病仍然是未知的。为了解决这个问题，我们首先通过免疫荧光和Western blot检测MAD2B和cyclin B1的表达。结果发现，高血糖可显著增加糖尿病大鼠模型大脑皮层及原代培养神经元中MAD2B的表达和cyclin B1的积累。为了进一步探索MAD2B在高脂血症诱导的神经元损伤中的作用，我们通过针对MAD2B的特异性靶向shRNA耗尽MAD2B表达。我们观察到，MAD2B缺陷减轻细胞周期蛋白B1的表达和凋亡神经元死亡。这些结果表明，MAD2B表达是高糖下神经元中细胞周期蛋白B1积累和凋亡的罪魁祸首。此外，MAD2B的表达抑制防止神经元进入异常的S期，导致分化的神经元凋亡细胞死亡。这些结果表明，高血糖通过诱导MAD2B的表达诱导神经细胞凋亡，这代表了糖尿病脑病的一种新机制。
Diabetic encephalopathy may lead to cognitive deficits in diabetic patients and diminish quality of life. It has been shown that protracted hyperglycaemia is directly associated with neuronal apoptosis, which is involved in diabetic encephalopathy. The anaphase‐promoting complex (APC) is essential for the survival of post‐mitotic neurons. In our previous study, we found that the mitotic arrest deficient protein MAD2B, one of APC inhibitors, was expressed in neurons in central nervous system. However, whether MAD2B is involved in hyperglycaemia‐induced apoptosis and thus takes part in diabetic encephalopathy is still unknown. To address this issue, we first explored the expression of MAD2B and cyclin B1 detected by immunofluorescence and Western blot. It was found that hyperglycaemia remarkably increased the expression of MAD2B and accumulation of cyclin B1 in cortices of diabetes mellitus rat model and in cultured primary neurons. To further explore the role of MAD2B in hyperglycaemia‐induced neuronal injury, we depleted MAD2B expression by a specifically targeted shRNA against MAD2B. We observed that MAD2B deficiency alleviated cyclin B1 expression and apoptotic neuronal death. These results demonstrate that MAD2B expression is the main culprit for accumulation of cyclin B1 and apoptosis in neurons under high glucose. Moreover, inhibition of the expression of MAD2B prevented neurons from entering an aberrant S phase that led differentiated neurons into apoptotic cell death. These results suggest that hyperglycaemia induced neuronal apoptosis through inducing expression of MAD2B, which represents a novel mechanism of diabetic encephalopathy.
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DOI：
10.1042/bj20112040
发表时间：
2012-06-15
期刊：
The Biochemical journal
影响因子：
--
作者：
Hindley C;Philpott A
通讯作者：
Philpott A
影响因子：
3.8
作者：
Kok, Kin Hang;Jin, Dong-Yan
通讯作者：
Jin, Dong-Yan
DOI：
10.3390/molecules16097980
发表时间：
2011-09-15
期刊：
Molecules (Basel, Switzerland)
影响因子：
--
作者：
Cavanagh BL;Walker T;Norazit A;Meedeniya AC
通讯作者：
Meedeniya AC
影响因子：
4
作者：
Casadesus, Gemma;Gutierrez-Cuesta, Javier;Pallas, Merce
通讯作者：
Pallas, Merce
影响因子：
5.1
作者：
Almeida, Angeles
通讯作者：
Almeida, Angeles