Open AccessProtection of neurons from high glucose‐induced injury by deletion of MAD 2B
Author(s) -
Meng Xianfang,
Wang Xiaolan,
Tian Xiujuan,
Yang Zhihua,
Li Man,
Zhang Chun
Publication year - 2014
Publication title -
journal of cellular and molecular medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.44
H-Index - 130
eISSN - 1582-4934
pISSN - 1582-1838
DOI - 10.1111/jcmm.12229
Subject(s) - apoptosis , cyclin b1 , mitosis , biology , programmed cell death , encephalopathy , neuron , microbiology and biotechnology , small hairpin rna , neuroscience , cell cycle , cancer research , medicine , gene knockdown , cyclin dependent kinase 1 , biochemistry
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 MAD 2B, one of APC inhibitors, was expressed in neurons in central nervous system. However, whether MAD 2B 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 MAD 2B and cyclin B1 detected by immunofluorescence and Western blot. It was found that hyperglycaemia remarkably increased the expression of MAD 2B and accumulation of cyclin B1 in cortices of diabetes mellitus rat model and in cultured primary neurons. To further explore the role of MAD 2B in hyperglycaemia‐induced neuronal injury, we depleted MAD 2B expression by a specifically targeted sh RNA against MAD 2B. We observed that MAD 2B deficiency alleviated cyclin B1 expression and apoptotic neuronal death. These results demonstrate that MAD 2B expression is the main culprit for accumulation of cyclin B1 and apoptosis in neurons under high glucose. Moreover, inhibition of the expression of MAD 2B 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 MAD 2B, which represents a novel mechanism of diabetic encephalopathy.