Novel interventions targeting on apoptosis and necrosis induced by aluminum chloride in neuroblastoma cells.
Aluminum chloride induces neuroblastoma cell (SH-SY5Y) death following in vitro exposure. The objective of this study is to define apoptosis and necrosis in an in vitro model system of SH-SY5Y cells, and to investigate appropriate defense mechanisms with caspase-3 small interference RNA (siRNA) and necrostatin-1 (Nec-1). SH-SY5Y cells were treated with aluminum chloride for 24 h, followed by analysis of cell death rates and alterations in morphology. The results show that aluminum chloride could induce cell death by a combination of apoptosis and necrosis. Treatment with caspase-3 siRNA resulted in inhibition of caspase-3 gene and protein expression, both indicatives of apoptosis reduction. In addition, decrement of apoptotic rate was evident. Interestingly, treatment with caspase-3 siRNA could markedly up-regulate the expression of LC3- II, indicating a shift of cell death mode, from apoptosis to autophagy. Nec-1 treatment significantly affected necrosis induced by aluminum chloride, resulting in decreased necrotic rates and marked inhibition of LC3- II expression. Results showed for the first time that cell death induced by aluminum chloride could be rescued by caspase-3 siRNA and Nec-1 in SH-SY5Y cells, and co-administration of both produced an additive effect on reducing cell death. These data will pave the way for future studies investigating the prevention of cell death in Al neurotoxicity both in vivo and in vitro.
Zhang
Q L
QL
Education Ministry Key Laboratory of Cell Physiology, Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, Shanxi, China.
Niu
Qiao
Q
Niu
P Y
PY
Ji
X L
XL
Zhang
C
C
Wang
L
L
D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D002712:Chlorides / Q000494:pharmacology*; D017931:DNA Primers; D006801:Humans; D008856:Microscopy, Fluorescence; D009336:Necrosis / Q000139:chemically induced*; D009447:Neuroblastoma / Q000201:enzymology / Q000235:genetics / Q000473:pathology*; D034741:RNA, Small Interfering / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017607:Aluminum Compounds; D002712:Chlorides; D017931:DNA Primers; D034741:RNA, Small Interfering; D000077410:Aluminum Chloride; D053148:Caspase 3