Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells.
Involvement of AMPK in regulating the degradation of MAD2B under high glucose in neuronal cells.
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AMPK参与调节神经细胞高糖下MAD2B的降解
DOI：
10.1111/jcmm.13046
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发表时间：
2017-06
影响因子：
5.3
通讯作者：
Zhang C
中科院分区：
文献类型：
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作者：
Meng X;Chu G;Ye C;Tang H;Qiu P;Hu Y;Li M;Zhang C
Although our recent study has demonstrated that mitotic spindle assembly checkpoint protein (MAD2B) mediates high glucose‐induced neuronal apoptosis, the mechanisms for MAD2B degradation under hyperglycaemia have not yet been elucidated. In this study, we first found that the activation of adenosine 5′‐monophosphate (AMP)‐activated protein kinase (AMPK) was decreased in neurons, accompanied with the increased expression of MAD2B. Mechanistically, we demonstrated that activation of AMPK with its activators such as AICAR and metformin decreased the expression of MAD2B, indicating a role of AMPK in regulating the expression of MAD2B. Moreover, activation of AMPK prevented neuronal cells from high glucose‐induced injury as demonstrated by the reduced expression of cyclin B1 and percentage of apoptosis as detected by TUNEL. We further found that when total protein synthesis was suppressed by chlorhexidine, the degradation of MAD2B was slower in high glucose‐treated neurons and was mainly dependent on the ubiquitin–proteasome system. Finally, it was indicated that high glucose inhibited the ubiquitination of MAD2B, which could be reversed by activation of AMPK. Collectively, this study demonstrates that AMPK acts as a key regulator of MAD2B expression, suggesting that activation of AMPK signalling might be crucial for the treatment of high glucose‐induced neuronal injury.
DOI：
10.1016/j.ijdevneu.2013.07.002
发表时间：
2013-11
期刊：
International journal of developmental neuroscience : the official journal of the International Society for Developmental Neuroscience
影响因子：
--
作者：
Wise A;Schatoff E;Flores J;Hua SY;Ueda A;Wu CF;Venkatesh T
通讯作者：
Venkatesh T