Pretreatment of SH-SY5Y cells with dicaffeoylquinic acids attenuates the reduced expression of nicotinic receptors, elevated level of oxidative stress and enhanced apoptosis caused by β-amyloid peptide.
OBJECTIVE
This in vitro investigation was designed to examine potential neuroprotection by dicaffeoylquinic acids (diCQAs) extracted from a traditional Chinese medicinal herb herba erigerontis and their effects against the toxicity induced by β-amyloid peptide (Aβ25-35 ).


METHODS
The neuroblastoma SH-SY5Y cell line was treated with Aβ or 3, 4-diCQA, 3, 5-diCQA or 4, 5-diCQA. 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) reduction was assayed by spectrophotometrical method, lipid peroxidation (malondialdehyde) on the basis of the level of thiobarbituric acid-reactive substance, the activity of superoxide dismutase by the xanthine oxidase procedure, the frequency of apoptosis by flow cytometry, and the levels of α3 and α7 nicotinic acetylcholine receptor (nAChR) subunit proteins by Western blotting.


RESULTS
When the cells were exposed to Aβ25-35 , MTT reduction declined, oxidative stress and apoptosis were enhanced, and the expression of α3 and α7 nAChR subunit proteins was lowered. Expression of the α7 nAChR subunit protein was increased by all three diCQAs, and the level of α3 was increased by 3, 5-diCQA and 4, 5-diCQA. Significantly, pretreatment with diCQAs attenuated the neurotoxic effects of Aβ25-35 , a neuroprotective effect in which the upregulation of α7 and α3 nAChR may be involved.


CONCLUSIONS
The diCQAs exert a protective effect on Aβ-induced neurotoxicity in SH-SY5Y cells and a potential underlying mechanism involving stimulation of nAChRs.
Department of Molecular Biology, Guiyang Medical College, Guiyang, China.
Jie
J
Deng
Xiao-Lan
XL
Qi
Zhi-Zhong
ZZ
Guan
Xiu-Ming
XM
Yan
Yong
Y
Huang
Yong-Lin
YL
Wang
D016229:Amyloid beta-Peptides / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D006801:Humans; D015227:Lipid Peroxidation / Q000187:drug effects; D009447:Neuroblastoma / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology*; D018384:Oxidative Stress; D011801:Quinic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D011978:Receptors, Nicotinic / Q000032:analysis*; D013482:Superoxide Dismutase / Q000378:metabolism
D016229:Amyloid beta-Peptides; D018696:Neuroprotective Agents; D017382:Reactive Oxygen Species; D011978:Receptors, Nicotinic; C472707:caffeoylquinic acid; D011801:Quinic Acid; D013482:Superoxide Dismutase
apoptosis; dicaffeoylquinic acids; lipid peroxidation; nicotinic acetylcholine receptor; β-amyloid peptide