Paraptosis triggers mitochondrial pathway-mediated apoptosis in Alzheimer's disease
Authors: Song Wang
Dong-Pei Jia
Fang Fang
Bao-Chao Zhang
Journal: Experimental and therapeutic medicine (2015)
Discipline: CLINICAL MEDICINE
Keywords: Alzheimer's disease; Bcl-2; cycloheximide; mitochondria-mediated apoptosis; paraptosis.
Affiliations: Department of Neurological Rehabilitation, Nanyang City Center Hospital, Nanyang, Henan 473003, P.R. China.

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 Œ≤-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&lt;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&gt;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. 

Retracted: Yes

PubPeer comments:
 Fig 4A.  Down-regulated ANRIL promoted the apoptotic index of HXO-RB44 cells and Y79 cells by Annexin V PI double staining method and flow cytometry (A) The cell apoptosis of HXO-RB44 cells in each group examined by flow cytometry .  Could the authors comment on the similarity to panels from Figure 4A of [Liu et al (2019)] ?  , 
 Expression of Concern, [26 March 2021] .  The Editorial Office has been made aware of potential issues surrounding the scientific validity of this paper, hence has issued an expression of concern to notify readers whilst the Editorial Office investigates. , 
 I don t want to slow the editors investigation, but they may also find it useful to examine the hand-drawn flow-cytometry plots of Fig 5A.  Also the stylised, string-of-sausages WBs of Figs 2 and 7.  , 
 Retracted, [13 September 2021] . -------------------------- This Retraction follows an Expression of Concern relating to this article previously published by Portland Press. This article is being retracted from Bioscience Reports at the request of the Editor-in-Chief and the Editorial Board following receipt of a notification from a reader, alerting the Editorial Board to duplicated data in Figure 4A which appears in another publication by different authors. The authors have been contacted in regards to the Retraction, and have not responded to the Journal s queries and the concerns raised. Given the extent of the issues raised, the Editorial Board stand by the decision to retract the article. ,