Effects of diazoxide on Aβ1-42-induced expression of the NR2B subunit in cultured cholinergic neurons.
The accumulation of amyloid-β protein (Aβ) is significant in the pathogenesis of Alzheimer's disease. Several previous studies indicate that the NR2B‑containing N‑methyl‑D‑aspartate receptors are critically involved in the Aβ mediated disruption of neuronal function. Diazoxide (DZ), a highly selective drug capable of opening mitochondrial ATP‑sensitive potassium channels, has neuroprotective effects against neuronal cell death. However, the mechanism by which DZ protects cholinergic neurons against Aβ‑induced cytotoxicity remains to be elucidated. The present study was designed to investigate the effects of DZ pretreatment against Aβ1‑42‑induced expression of NR2B in order to gain novel insights into the neuroprotective mechanisms. Following exposure to Aβ1‑42 for 24 h, the expression of the NR2B subunit remained unchanged compared with the control group. However, a significant increase in the expression of the NR2B subunit was observed following treatment with Aβ1‑42 for 72 h (P<0.05); and the upregulation of the expression of the NR2B subunit was reversed by pretreatment with DZ (P<0.05). These results suggested that DZ may counteract Aβ1‑42‑mediated cytotoxicity by alleviating the expression of NR2B.
Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shangdong 250014, P.R. China.
Jin
J
Zhu
Department of Neurology, Linyi People's Hospital, Linyi, Shandong 276003, P.R. China.
Qingxi
Q
Fu
Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shangdong 250014, P.R. China.
Chunfeng
C
Xia
Department of Neurology, Shandong Provincial Qianfoshan Hospital, Shandong University, Jinan, Shangdong 250014, P.R. China.
Guozhao
G
Ma
D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D059329:Cholinergic Neurons / Q000187:drug effects* / Q000378:metabolism; D003981:Diazoxide / Q000494:pharmacology*; D005260:Female; D018696:Neuroprotective Agents / Q000494:pharmacology*; D010446:Peptide Fragments / Q000378:metabolism*; D015221:Potassium Channels / Q000378:metabolism; D017208:Rats, Wistar; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*
D016229:Amyloid beta-Peptides; C121001:NR2B NMDA receptor; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D015221:Potassium Channels; D016194:Receptors, N-Methyl-D-Aspartate; C075222:amyloid beta-protein (1-42); C117780:mitochondrial K(ATP) channel; D003981:Diazoxide