Involvement of ubiquitin proteasome system in protective mechanisms of Puerarin to MPP(+)-elicited apoptosis.
It has been well documented that dysfunction of ubiquitin proteasome system (UPS) in the neuron exacerbated the Parkinson's disease (PD). However, whether or not UPS is involved in the protective effect of Puerarin on 1-Methyl-4-Phenyl-1, 2, 3, 6-Tetrahydropyridine (MPP(+))-elicited cell death is yet to be elucidated. In this study, treatment of SH-SY5Y cells with 1mM MPP(+)-elicited a characteristic apoptotic cell death and pretreatment with Puerarin protected cells against MPP(+)-induced apoptosis as evidenced by promoting cell viability, improving morphological changes and reducing apoptotic rate. To further explore the potential protective mechanism of Puerarin in MPP(+)-induced SH-SY5Y cell death, UPS activity, mitochondria-dependent apoptosis and caspase-3 activity were measured. Puerarin pretreatment attenuated MPP(+)-induced dysfunction of protease activity, thereby reducing accumulation of ubiquitin-conjugated proteins. Meanwhile, caspase-3 activity was remarkably attenuated by Puerarin. In addition, the ratio of bcl-2/bax was increased by Puerarin in comparison with MPP(+)-treated group. Taken together, these results suggest that Puerarin could protect MPP(+)-induced SH-SY5Y cells from apoptosis by regulating the function of UPS.
Cheng
Yue-Fa
YF
Dept of Pharmacology, Anhui Medical University, Hefei 230032, People's Republic of China.
Zhu
Guo-Qi
GQ
Wang
Mei
M
Cheng
Hui
H
Zhou
An
A
Wang
Ning
N
Fang
Nianbai
N
Wang
Xun-Cui
XC
Xiao
Xiao-Qiu
XQ
Chen
Zhi-Wu
ZW
Li
Qing-Lin
QL
D015655:1-Methyl-4-phenylpyridinium / Q000037:antagonists & inhibitors / Q000633:toxicity; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D051017:Apoptosis Regulatory Proteins / Q000187:drug effects / Q000378:metabolism; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D006540:Herbicides / Q000037:antagonists & inhibitors / Q000633:toxicity; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D015394:Molecular Structure; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D010300:Parkinson Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects* / Q000378:metabolism; D025801:Ubiquitin / Q000187:drug effects* / Q000378:metabolism; D054875:Ubiquitination / Q000187:drug effects / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
D051017:Apoptosis Regulatory Proteins; D006540:Herbicides; D007529:Isoflavones; D018696:Neuroprotective Agents; D025801:Ubiquitin; D014665:Vasodilator Agents; D053148:Caspase 3; D046988:Proteasome Endopeptidase Complex; D015655:1-Methyl-4-phenylpyridinium; C033607:puerarin