title: Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease.
abstract: In previous years, increasing evidence has indicated that paraptosis and mitochondrial-mediated apoptosis may be associated with Alzheimer's disease (AD). However, the association between paraptosis and mitochondrial-mediated apoptosis, and the pathological processes underlying AD, remain elusive. In the present study, the β-amyloid precursor protein gene, and the gene mutations PS1M146L and L286V, were transfected to an SH-SY5Y cell line to establish an AD cell model. Subsequently, an MTT assay was used to examine the cell viability of the AD cell model, while a TUNEL assay was employed to observe the number of positively stained apoptotic cells. Cytoplasmic vacuolization was examined using light microscopy and images were photographed. Furthermore, western blot analysis was utilized to detect the expression of golden biomarkers of the mitochondrial pathway, including Bcl-2 and Bax. The paraptosis inhibitor, cycloheximide, was selected to treat the AD model cells in order to observe the association between paraptosis and mitochondrial-mediated apoptosis. The results indicated that the decrease in the cell viability of the AD cells was initiated at 24 h, as compared with the normal cells (P<0.05). TUNEL-positive stained cells were observed at 48 h, which was later compared with the cell death initiation. In addition, examination of cytoplasmic vacuolization using microscopy indicated that there were a small number of paraptosis cells present at 24 h. The expression levels of Bcl-2 was significantly decreased, while Bax was significantly increased at 48 h. Furthermore, cycloheximide treatment was demonstrated to significantly increase Bcl-2 expression, while decreasing Bax expression (P>0.05). In conclusion, the occurrence of paraptosis was demonstrated in the early pathological stages of AD, which may subsequently damage the mitochondria and trigger mitochondrial pathway-mediated apoptosis. Thus, paraptosis may trigger programmed cell death directly, or indirectly through the regulation of Bcl-2 and Bax protein expression.
authors.affiliation: Department of Neurological Rehabilitation, Nanyang City Center Hospital, Nanyang, Henan 473003, P.R. China.
authors.forename: Dong-Pei
authors.initials: DP
authors.lastname: Jia
authors.affiliation: Department of Neurological Rehabilitation, Nanyang City Center Hospital, Nanyang, Henan 473003, P.R. China.
authors.forename: Song
authors.initials: S
authors.lastname: Wang
authors.affiliation: Department of Neurological Rehabilitation, Nanyang City Center Hospital, Nanyang, Henan 473003, P.R. China.
authors.forename: Bao-Chao
authors.initials: BC
authors.lastname: Zhang
authors.affiliation: Department of Neurological Rehabilitation, Nanyang City Center Hospital, Nanyang, Henan 473003, P.R. China.
authors.forename: Fang
authors.initials: F
authors.lastname: Fang
keywords: Alzheimer's disease; Bcl-2; cycloheximide; mitochondria-mediated apoptosis; paraptosis