Protection of neurons from high glucose-induced injury by deletion of MAD2B
Article first published online: 20 JAN 2014
© 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Journal of Cellular and Molecular Medicine
Volume 18, Issue 5, pages 844–851, May 2014
How to Cite
Meng, X., Wang, X., Tian, X., Yang, Z., Li, M. and Zhang, C. (2014), Protection of neurons from high glucose-induced injury by deletion of MAD2B. Journal of Cellular and Molecular Medicine, 18: 844–851. doi: 10.1111/jcmm.12229
- Issue published online: 15 MAY 2014
- Article first published online: 20 JAN 2014
- Manuscript Accepted: 9 DEC 2013
- Manuscript Received: 28 JUL 2013
- National Natural Science Foundation of China. Grant Numbers: 30871174, 81170662, 81170600, 81300604
- Natural Science Foundation of Hubei Province. Grant Numbers: 2013CFA026, 2012FFA038
- Doctoral Fund of Ministry of Education of China. Grant Number: 20130142110064
- Fundamental Research Funds for the Central Universities. Grant Number: 2013QN176
- cyclin B1;
- neuronal injury
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.