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Glutaminyl cyclase inhibitor contributes to the regulation of HSP70, HSP90, actin, and ribosome on gene and protein levels in vitro
Author(s) -
Yu Xi,
Li Yue,
Zou Yongdong,
Zheng Yizhi,
He Zhendan,
Liu Zhigang,
Xie Wenlin,
Wu Haiqiang
Publication year - 2019
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.28222
Subject(s) - hsp70 , transcriptome , gene , gene expression , heat shock protein , microbiology and biotechnology , in vitro , biology , translation (biology) , hsp90 , protein biosynthesis , messenger rna , chemistry , biochemistry
Because of the crucial roles of upregulated glutaminyl cyclase (QC) in the initiation and development of Alzheimer's disease (AD), QC inhibitors are supposed as disease‐modifying agents for the treatment of AD. And reported compounds encourage this hypothesis greatly based on the remarkable anti‐AD effects in vivo. To illustrate the mechanism in detail, the actions of a selected QC inhibitor ( 23 ) were assessed firstly in a cell system here. It was demonstrated that QC activities and the generation of pyroglutamate‐modified β‐amyloids in PC12 cells were both inhibited obviously after the treatment of 23 . A total of 13 and 15 genes were up‐ and downregulated significantly in treated cells by RNA‐sequencing analysis. Quantitative real‐time polymerase chain reaction, enzyme‐linked immunosorbent assay, WB, and immunouorescence analysis supported the effects of 23 on the transcriptome of PC12 cells consequently. The expressions of chaperones, heat shock proteins (HSP) 70, and 90, were upreglutated, while gene expression of actin and the level of encoded protein were reduced significantly in PC12 cells with the treatment. Furthermore, the regulations of ribosome were observed after the treatment. These results indicate the potency of 23 to improve the translation, expression and folding regulation of proteins and affect the multivalent cross‐linking of cytoskeletal protein and other proteins subsequently in the cell system and might contribute to the understanding of the mechanism of QC inhibitor as potential anti‐AD agents.