alpha-Synuclein overexpression during manganese-induced apoptosis in SH-SY5Y neuroblastoma cells.
Chronic inorganic manganese (Mn) exposure has been known to induce neurological disorders similar to Parkinson's disease (PD). Apoptosis has been shown to be involved in manganese-induced neurotoxicity. However, the up-stream molecular mechanisms for cell apoptosis are not established. alpha-Synuclein (alpha-syn) is a major component of intracellular inclusions in PD, Alzheimer's disease (AD), and other neurodegenerative disorders. We investigated the role of alpha-syn in manganese chloride (MnCl(2))-induced apoptosis. Results show that MnCl(2) enhanced transcriptional and translational alpha-syn overexpression, and apoptosis as measured by caspase-3 activity and flow cytometry. Overexpressing alpha-syn exacerbated manganese-induced apoptosis, whereas antisense alpha-syn treatment significantly reversed MnCl(2)-induced apoptosis in human neuroblastoma SH-SY5Y cells. In conclusion, our results imply that intracellular alpha-syn overexpression may be responsible for MnCl(2)-induced apoptosis.
Li
Yan
Y
Department of Biochemical and Molecular Biology, China Medical University, Shenyang City 110001, Liaoning Province, China.
Sun
Liguang
L
Cai
Tongjian
T
Zhang
Ying
Y
Lv
Shijie
S
Wang
Yu
Y
Ye
Liping
L
D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology*; D015153:Blotting, Western; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D002712:Chlorides / Q000633:toxicity*; D006801:Humans; D017895:Manganese Compounds; D014176:Protein Biosynthesis / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014131:Trace Elements / Q000633:toxicity*; D014158:Transcription, Genetic / Q000187:drug effects; D051844:alpha-Synuclein / Q000378:metabolism*
D017304:Annexin A5; D002712:Chlorides; D017895:Manganese Compounds; D012333:RNA, Messenger; D014131:Trace Elements; D051844:alpha-Synuclein; C505407:CASP3 protein, human; D053148:Caspase 3; C025340:manganese chloride