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3-(Naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride attenuates MPP+-induced cytotoxicity by regulating oxidative stress and mitochondrial dysfunction in SH-SY5Y cells

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Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4- phenylpyridinium (MPP+)-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against MPP+-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated MPP+-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of MPP+-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, Ca2+, and ATP in MPP+-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against MPP+-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

Abstract

Parkinson's disease (PD) is a common chronic neurodegenerative disease mainly caused by the death of dopaminergic neurons. However, no complete pharmacotherapeutic approaches are currently available for PD therapies. 1-methyl-4- phenylpyridinium (MPP+)-induced SH-SY5Y neurotoxicity has been broadly utilized to create cellular models and study the mechanisms and critical aspects of PD. In the present study, we examined the role of a novel azetidine derivative, 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride (KHG26792), against MPP+-induced neurotoxicity in SH-SY5Y cells. Treatment of KHG26792 significantly attenuated MPP+-induced changes in the protein levels of Bcl-2 and Bax together with efficient suppression of MPP+-induced activation of caspase-3 activity. KHG26792 also attenuated mitochondrial potential and levels of ROS, Ca2+, and ATP in MPP+-treated SH-SY5Y cells. Additionally, KHG26792 inhibited the induced production of nitric oxide and malondialdehyde. Moreover, the protective effect of KHG26792 is mediated through regulation of glutathione peroxidase and GDNF levels. Our results suggest a possibility that KHG26792 treatment significantly protects against MPP+-induced neurotoxicity in SH-SY5Y cells and KHG26792 may be a valuable therapeutic agent for the treatment of PD induced by an environmental toxin.

참고문헌 (30)

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사람 신경모세포종 SH-SY5Y 세포주의 파킨슨 모델에 대한 小續命湯의 보호효과우찬, 김효린, 문아지, 신선호, 신용진, 유주연, 장철용대한한방내과학회 · 대한한방내과학회지2014 · 제35권 제3호Anti-inflammatory and anti-oxidative effects of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on β-amyloid-induced microglial activation김지애, 안지인, 양승주, 이상은, 조성우, 최수영생화학분자생물학회 · BMB Reports2017 · 제50권 제12호Rotundarpene이 파킨슨증 유발 신경독소1-methyl-4-phenylpyridinium에 의한 세포자멸사에 미치는 억제효과김두응, 이정수, 한상우, 한정호, 황인하대한신경과학회 · 대한신경과학회지2016 · 제34권 제4호Protective effects of PEP-1-Catalase on stress-induced cellular toxicity and MPTP-induced Parkinson’s disease권혁일, 김대원, 김덕수, 박진서, 손은정, 신민재, 안은희, 엄선애, 음원식, 전수정, 정석영, 조성우, 조효상, 최수영, 한규형생화학분자생물학회 · BMB Reports2015 · 제48권 제7호Protective effect of 3-(naphthalen-2-yl(propoxy)methyl)azetidine hydrochloride on hypoxia-induced toxicity by suppressing microglial activation in BV-2 cells김수민, 김지애, 나정민, 양승주, 조성우, 한호규생화학분자생물학회 · BMB Reports2016 · 제49권 제12호3,4,5-Tricaffeoylquinic acid가 파킨슨증후군유발독소 1-methyl-4-phenylpyridinium에 의한세포자멸사에 미치는 억제효과강진호, 김두응, 이정수, 주재정, 한정호대한신경과학회 · 대한신경과학회지2014 · 제32권 제2호

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