Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity

We examined synergistic effects of inhibiting reactive oxygen species generated from the mitochondria and from nicotinamide adenine dinucleotide phosphate oxidase on neurotoxicity. Primary hippocampal neurons were exposed to amyloid β, and the cells were treated with diazoxide or/and diphenyleneiodo...

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Main Authors: Qingxi Fu, Naiyong Gao, Fengyuan Che, Guangyin Xu, Hongxing Han, Quanping Su, Guozhao Ma
Format: Article
Language:English
Published: IMR Press 2019-12-01
Series:Journal of Integrative Neuroscience
Subjects:
Online Access: https://jin.imrpress.com/fileup/1757-448X/PDF/1577791324315-850926386.pdf
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author Qingxi Fu
Naiyong Gao
Fengyuan Che
Guangyin Xu
Hongxing Han
Quanping Su
Guozhao Ma
author_facet Qingxi Fu
Naiyong Gao
Fengyuan Che
Guangyin Xu
Hongxing Han
Quanping Su
Guozhao Ma
author_sort Qingxi Fu
collection DOAJ
description We examined synergistic effects of inhibiting reactive oxygen species generated from the mitochondria and from nicotinamide adenine dinucleotide phosphate oxidase on neurotoxicity. Primary hippocampal neurons were exposed to amyloid β, and the cells were treated with diazoxide or/and diphenyleneiodonium chloride. We found that the cell viability was decreased significantly after exposure to amyloid β for 72 h with higer reactive oxygen species and malondialdehyde levels, higher caspase-3 and cleaved caspase-3 levels and lower B-cell lymphoma 2 (Bcl-2) level. Both diazoxide and diphenyleneiodonium increased cell viability by inhibiting the increase in reactive oxygen species and caspase-3 activity as well as the decrease in Bcl-2 induced by amyloid β. The combination of diazoxide and diphenyleneiodonium exhibited better protective effects compared to a single treatment. In conclusion, the activation of a mitochondrial potassium channel in combination with the inhibitor of nicotinamide adenine dinucleotide phosphate oxidase exhibit synergistic protective effects against amyloid β neurotoxicity.
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spelling doaj.art-d09bcfaa405c46699e939c1f6fb2b7822022-12-22T00:26:51ZengIMR PressJournal of Integrative Neuroscience0219-63521757-448X2019-12-0118444544910.31083/j.jin.2019.04.11741577791324315-850926386Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicityQingxi Fu0Naiyong Gao1Fengyuan Che2Guangyin Xu3Hongxing Han4Quanping Su5Guozhao Ma6 Deparment of Neurology, Linyi People's Hospital, Shandong Province, 276003, P. R. China Deparment of Neurology, Linyi People's Hospital, Shandong Province, 276003, P. R. China Deparment of Neurology, Linyi People's Hospital, Shandong Province, 276003, P. R. China Deparment of Neurology, Linyi People's Hospital, Shandong Province, 276003, P. R. China Deparment of Neurology, Linyi People's Hospital, Shandong Province, 276003, P. R. China Central Laboratory, Linyi People's Hospital, Shandong Province, 276003, P. R. China Deparment of Neurology, East Hospital, Tongji University School of Medicine, Shanghai, 200120, P. R. China We examined synergistic effects of inhibiting reactive oxygen species generated from the mitochondria and from nicotinamide adenine dinucleotide phosphate oxidase on neurotoxicity. Primary hippocampal neurons were exposed to amyloid β, and the cells were treated with diazoxide or/and diphenyleneiodonium chloride. We found that the cell viability was decreased significantly after exposure to amyloid β for 72 h with higer reactive oxygen species and malondialdehyde levels, higher caspase-3 and cleaved caspase-3 levels and lower B-cell lymphoma 2 (Bcl-2) level. Both diazoxide and diphenyleneiodonium increased cell viability by inhibiting the increase in reactive oxygen species and caspase-3 activity as well as the decrease in Bcl-2 induced by amyloid β. The combination of diazoxide and diphenyleneiodonium exhibited better protective effects compared to a single treatment. In conclusion, the activation of a mitochondrial potassium channel in combination with the inhibitor of nicotinamide adenine dinucleotide phosphate oxidase exhibit synergistic protective effects against amyloid β neurotoxicity. https://jin.imrpress.com/fileup/1757-448X/PDF/1577791324315-850926386.pdf alzheimer's diseasediphenyleneiodoniumpotassium channelreactive oxygen speciesneurotoxicity
spellingShingle Qingxi Fu
Naiyong Gao
Fengyuan Che
Guangyin Xu
Hongxing Han
Quanping Su
Guozhao Ma
Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
Journal of Integrative Neuroscience
alzheimer's disease
diphenyleneiodonium
potassium channel
reactive oxygen species
neurotoxicity
title Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
title_full Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
title_fullStr Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
title_full_unstemmed Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
title_short Diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
title_sort diphenyleneiodonium chloride synergizes with diazoxide to enhance protection against amyloid β induced neurotoxicity
topic alzheimer's disease
diphenyleneiodonium
potassium channel
reactive oxygen species
neurotoxicity
url https://jin.imrpress.com/fileup/1757-448X/PDF/1577791324315-850926386.pdf
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