title: Is necroptosis a death pathway in aluminum-induced neuroblastoma cell demise?
abstract: Besides being an aggravating factor secondary to major physiological alterations in degenerative diseases, aluminum has also been considered as a risk factor in the etiology. Although many in vivo and in vitro data are in favor of apoptosis and necrosis being involved in Al induced neurodegenerative processes, there is considerable evidence that very complex events may contribute to neural cell death. Necroptosis, a novel cell death pathway, was recently reported to contribute to ischemia brain injury. It is different from, but associated with, apoptosis and necrosis, the two common major pathways of cell demise. In the present study, SH-SY5Y cells were put under stress by Al, a potential degenerative cell death inducer. Nec-1, a specific inhibitor, was used to identify necroptosis. The characteristics observed in Nec-1 and Al treated SH-SY5Y cells showed that necrotic morphological changes were reduced, and a sharp decrease of necrotic rate was detected. Besides, there were Al-induced mitochondria membrane potential decreasing, reactive oxygen species remaining, and autophagosomes declining. The mechanism of Nec-1s effect on cell death may be related to caspases pathways. To our best knowledge, this is the pioneer report on necroptosis in mixed human neural cell death pathways, which might offer a novel therapeutic target for neurodegenerative diseases, and an extended window for neuroprotection.
authors.affiliation: Department of Occupational Health, School of Public Health, Shanxi Medical University, Taiyuan, China.
authors.forename: Q L
authors.initials: QL
authors.lastname: Zhang
authors.forename: Q
authors.initials: Q
authors.lastname: Niu
authors.forename: X L
authors.initials: XL
authors.lastname: Ji
authors.forename: P
authors.initials: P
authors.lastname: Conti
authors.forename: P
authors.initials: P
authors.lastname: Boscolo
mesh_terms: D000535:Aluminum / Q000633:toxicity*; D017209:Apoptosis; D053148:Caspase 3 / Q000378:metabolism; D045744:Cell Line, Tumor; D005434:Flow Cytometry; D006801:Humans; D046529:Microscopy, Electron, Transmission; D009336:Necrosis; D009447:Neuroblastoma / Q000139:chemically induced* / Q000201:enzymology / Q000473:pathology
chemical_list: D000535:Aluminum; D053148:Caspase 3