Protection of neurons from high glucose-induced injury by deletion of MAD2B.
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.
Department of Neurobiology, School of Basic Medical Sciences, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Xianfang
X
Meng
Xiaolan
X
Wang
Xiujuan
X
Tian
Zhihua
Z
Yang
Man
M
Li
Chun
C
Zhang
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002540:Cerebral Cortex / Q000473:pathology; D056744:Cyclin B1 / Q000378:metabolism; D017353:Gene Deletion; D020868:Gene Silencing / Q000187:drug effects; D005947:Glucose / Q000633:toxicity*; D006943:Hyperglycemia / Q000378:metabolism; D064246:Mad2 Proteins / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology*; D018696:Neuroprotective Agents / Q000378:metabolism*; D055550:Protein Stability / Q000187:drug effects; D017207:Rats, Sprague-Dawley; D016196:S Phase / Q000187:drug effects
D056744:Cyclin B1; D064246:Mad2 Proteins; D018696:Neuroprotective Agents; D005947:Glucose
MAD2B; cyclin B1; hyperglycaemia; neuronal injury