title: [MAPK signaling pathways involved in aluminum-induced apoptosis and necroptosis in SH-SY5Y cells].
abstract: OBJECTIVE
  To explore the role of MAPK signaling pathway in apoptosis and necroptosis induced by aluminum in SH-SY5Y cells.
  
  
  METHODS
  To imitate neural cell death induced by aluminium, AlCl3 x 6H2O (4 mmol/L) was used to treat SH-SY5Y cells. Necrostatin-1 (Nec-1,60 μmol/L), the specific inhibitor for necroptosis, and zVAD-fmk (20 μmol/L), the specific inhibitor for apoptosis, were added into cultures for inhibiting the occurrence of necroptosis and apoptosis. CCK-8 was performed to measure cell viability, flow cytometry was used to test the difference of apoptosis rate and necrosis rate between groups, and western-blot was used to detect the change of MAPK protein.
  
  
  RESULTS
  Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, cell viabiligy of Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group decreaced (P < 0.05). Compared with Al(3+) exposed group, cell viability of Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group increased (P < 0.05). Necrotic rate and apoptotic rate in Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group obviously increased compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group (P < 0.05). Compared with Al(3+) exposed group, necrotic and apaptotic rate of Al(3+) plus zVAD-fmk group and Al(3+) plus Nec-1 group were statistically significant decreased (P < 0.05). Compared with blank control group, solvent control group, Nec-1 control group and zVAD-fmk control group, expression of p-p38 in Al(3+) exposed group, Al(3+) plus Nec-1 group and Al(3+) plus zVAD-fmk group increased obviously (P < 0.05), and expression of p-ERK decreased significantly (P < 0.05). Compared with Al(3+) exposed group, expression of p-p38 decreased (P < 0.05), but p-ERK increased in Al(3+) plus Nec-1 group (P < 0.05).
  
  
  CONCLUSIONS
  The ERK and p38 MAPK signaling pathways are involved in aluminum-induced necroptosis in SH-SY5Y cells, but only ERK signaling pathway is involved in aluminum-induced apoptosis, and JNK signaling pathway is not involved in aluminum-induced cell death.
authors.affiliation: Department of Occupation Health, School of Public Health, Shanxi Medical University, Taiyuan 030001, China. jiaxiaofang2008@163.com
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Jia
authors.forename: Qinli
authors.initials: Q
authors.lastname: Zhang
authors.forename: Qiao
authors.initials: Q
authors.lastname: Niu
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000590:Amino Acid Chloromethyl Ketones; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D016923:Cell Death / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D002712:Chlorides; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D007211:Indoles / Q000494:pharmacology; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism; D009447:Neuroblastoma; D015398:Signal Transduction
chemical_list: D017607:Aluminum Compounds; D000590:Amino Acid Chloromethyl Ketones; D002712:Chlorides; D007093:Imidazoles; D007211:Indoles; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; C507699:necrostatin-1; D000077410:Aluminum Chloride; D000535:Aluminum; D020929:Mitogen-Activated Protein Kinase Kinases