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Effect of Beta‐amyloid on cell death‐related molecules: Is the co‐chaperone BAG2 a potential target for Alzheimer's disease?
Author(s) -
Carrettiero Daniel Carneiro,
Fardin Nubia M,
Carmo Ramon Torreglosa,
Almeida Maria Camila
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.802.50
Subject(s) - relb , gene knockdown , apoptosis , microbiology and biotechnology , chemistry , sh sy5y , messenger rna , programmed cell death , cell culture , biology , nfkb1 , biochemistry , gene , transcription factor , genetics , neuroblastoma
Alzheimer's disease is characterized by abnormal accumulation of extracellular beta‐amyloid plaques (Aβ). Aβ promotes cell death and NF‐κB signaling activation. Because BAG2 is repressed by NF‐κB signaling, the aim of the present study was to investigate the effect of Aβ/BAG2 on cell death‐related molecules such as NF‐κBp65, BAX, Bcl‐2, and Bcl‐3 in hippocampal primary cell culture and in differentiated and non‐differentiated SH‐SY5Y cells. In addition, we also investigate the effect of Aβ/BAG2 on NFκB1, NFκB2, RELA, and RELB gene expression. Western blotting and qPCR were used in the present project after Aβ stimulation with BAG2 overexpression or BAG2 knockdown. Aβ toxicity was increased in BAG2 overexpressing cells and was decreased after mRNA BAG2 knockdown. Aβ treatment promotes an increase in pNF‐kBp65/NF‐kBp65 suggesting nuclear translocation of this molecule and possible gene activation independently of BAG2. Pro‐apoptotic BAX and anti‐apoptotic Bcl‐2 proteins and mRNA were analyzed in Aβ‐stimulated cells with BAG2 knockdown. Aβ treatment resulted in an increase in BAX which was reversed in mRNA BAG2 knockdown cells, but no significant effect was detected in Bcl‐2 or Bcl‐3 levels. The effect of Aβ in differentiated compared to non‐differentiated SH‐SY5Y cells were distinct. Aβ treatment, in differentiated SH‐SY5Y cells, resulted in an increase of NFKB1, NFKB2, and RELA which was reversed in mRNA BAG2 knockdown cells. No significant effect was detected in RELB levels. On the other hand, in non‐differentiated SH‐SY5Y cells, Aβ treatment resulted in a decrease in NFκB1, NFκB2 and increase in RELB which was reversed in mRNA BAG2 knockdown cells. Our data suggests BAG2 an important molecule related to Aβ toxicity and NF‐κB signaling activation. BAG2 increased Aβ toxicity, probably interacting with the transcription factor NF‐κB in the NF‐κB nuclear translocation, and resulted in activation of pro‐apoptotic BAX leading to the expression of several cell death‐related molecules. Nevertheless, this effect seems to be differentially activated in differentiated and non‐differentiated SH‐SY5Y cells. Support or Funding Information FAPESP (grant 2015/23426‐9) This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .