Preventive effects of imperatorin on perfluorohexanesulfonate-induced neuronal apoptosis via inhibition of intracellular calcium-mediated ERK pathway
The Korean Journal of Physiology and Pharmacology
; : 399-406, 2016.
Article
in English
| WPRIM (Western Pacific)
| ID: wpr-728432
Responsible library:
WPRO
ABSTRACT
Early life neuronal exposure to environmental toxicants has been suggested to be an important etiology of neurodegenerative disease development. Perfluorohexanesulfonate (PFHxS), one of the major perfluoroalkyl compounds, is widely distributed environmental contaminants. We have reported that PFHxS induces neuronal apoptosis via ERK-mediated pathway. Imperatorin is a furanocoumarin found in various edible plants and has a wide range of pharmacological effects including neuroprotection. In this study, the effects of imperatorin on PFHxS-induced neuronal apoptosis and the underlying mechanisms are examined using cerebellar granule cells (CGC). CGC were isolated from seven-day old rats and were grown in culture for seven days. Caspase-3 activity and TUNEL staining were used to determine neuronal apoptosis. PFHxS-induced apoptosis of CGC was significantly reduced by imperatorin and PD98059, an ERK pathway inhibitor. PFHxS induced a persistent increase in intracellular calcium, which was significantly blocked by imperatorin, NMDA receptor antagonist, MK801 and the L-type voltage-dependent calcium channel blockers, diltiazem and nifedipine. The activation of caspase-3 by PFHxS was also inhibited by MK801, diltiazem and nifedipine. PFHxS-increased ERK activation was inhibited by imperatorin, MK801, diltiazem and nifedipine. Taken together, imperatorin protects CGC against PFHxS-induced apoptosis via inhibition of NMDA receptor/intracellular calcium-mediated ERK pathway.
Full text:
Available
Health context:
Sustainable Health Agenda for the Americas
Health problem:
Goal 9: Noncommunicable diseases and mental health
Database:
WPRIM (Western Pacific)
Main subject:
Plants, Edible
/
Calcium Channel Blockers
/
Diltiazem
/
Nifedipine
/
Calcium
/
Dizocilpine Maleate
/
N-Methylaspartate
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Apoptosis
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Neurodegenerative Diseases
/
In Situ Nick-End Labeling
Limits:
Animals
Language:
English
Journal:
The Korean Journal of Physiology and Pharmacology
Year:
2016
Document type:
Article