Manganese induces the overexpression of α-synuclein in PC12 cells via ERK activation.
Manganese has been known to induce neurological disorders. In the present study, we determined the effect of manganese on the expression of α-synuclein in PC12 cells and its role in manganese-induced cytotoxicity. We also investigated the relationship between α-synuclein expression and the change of ERK1/2 MAPK activity. In our research, manganese exposure induced the overexpression of α-synuclein, while siRNA knockdown of α-synuclein reversed manganese-induced cytotoxicity. Furthermore, manganese induced the activation of ERK1/2 MAPK. The MEK1 inhibitor PD98059, which inhibits the activation of ERK MAPK, attenuated the overexpression of α-synuclein and the cytotoxicity induced by manganese. In conclusion, our studies show that manganese may induce the overexpression of α-synuclein via ERK1/2 activation, which may play a role in manganese-induced cytotoxicity.
Cai
Tongjian
T
Department of Occupational and Environmental Health, School of Public Health, Fourth Military Medical University, Xi'an 710032, China.
Yao
Ting
T
Zheng
Gang
G
Chen
Yaoming
Y
Du
Kejun
K
Cao
Yunxin
Y
Shen
Xuefeng
X
Chen
Jingyuan
J
Luo
Wenjing
W
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D015153:Blotting, Western; D002469:Cell Separation; D004789:Enzyme Activation / Q000187:drug effects; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects* / Q000378:metabolism; D005434:Flow Cytometry; D008345:Manganese / Q000633:toxicity*; D016716:PC12 Cells; D034622:RNA Interference; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D014131:Trace Elements / Q000633:toxicity*; D051844:alpha-Synuclein / Q000096:biosynthesis*
D014131:Trace Elements; D051844:alpha-Synuclein; D008345:Manganese; D048049:Extracellular Signal-Regulated MAP Kinases