Molecular Mechanism of the ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuronal Apoptosis in SPS Rats.

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Abstrakt

Tytuł:: Molecular Mechanism of the ATF6α/S1P/S2P Signaling Pathway in Hippocampal Neuronal Apoptosis in SPS Rats.
Autorzy:: Han L; PTSD Laboratory, Department of Histology and Embryology, School of Basic Medicine, China Medical University, Shenyang, China.; Department of Thoracic Surgery, Third Affiliated Hospital of Jinzhou Medical University, Jinzhou, China.
Xu Y; PTSD Laboratory, Department of Histology and Embryology, School of Basic Medicine, China Medical University, Shenyang, China.
Shi Y; PTSD Laboratory, Department of Histology and Embryology, School of Basic Medicine, China Medical University, Shenyang, China. .
Źródło:: Journal of molecular neuroscience : MN [J Mol Neurosci] 2021 Dec; Vol. 71 (12), pp. 2487-2499. Date of Electronic Publication: 2021 Mar 18.
Typ publikacji:: Journal Article
Język:: English
Imprint Name(s):: Publication: Totowa, NJ : Humana Press
Original Publication: Boston : Birkhäuser [i.e. Cambridge, MA : Birkhäuser Boston, c1989-
MeSH Terms:: Apoptosis*
Activating Transcription Factor 6/*metabolism
Hippocampus/*metabolism
Proprotein Convertases/*metabolism
Serine Endopeptidases/*metabolism
Stress Disorders, Post-Traumatic/*metabolism
Activating Transcription Factor 6/genetics ; Animals ; Caspase 12/genetics ; Caspase 12/metabolism ; Endoplasmic Reticulum Stress ; Heat-Shock Proteins/genetics ; Heat-Shock Proteins/metabolism ; Hippocampus/cytology ; Male ; Memory ; Neurons/metabolism ; Proprotein Convertases/genetics ; Rats ; Rats, Wistar ; Serine Endopeptidases/genetics ; Signal Transduction ; Stress Disorders, Post-Traumatic/genetics ; Transcription Factor CHOP/genetics ; Transcription Factor CHOP/metabolism
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Contributed Indexing:: Keywords: Activating transcription factor 6α; Hippocampus; Posttraumatic stress disorder; Single prolonged stress
Substance Nomenclature:: 0 (Activating Transcription Factor 6)
0 (Atf6 protein, rat)
0 (Ddit3 protein, rat)
0 (GRP78 protein, rat)
0 (Heat-Shock Proteins)
147336-12-7 (Transcription Factor CHOP)
EC 3.4.21.- (Proprotein Convertases)
EC 3.4.21.- (Serine Endopeptidases)
EC 3.4.21.112 (membrane-bound transcription factor peptidase, site 1)
EC 3.4.22.- (Caspase 12)
Entry Date(s):: Date Created: 20210319 Date Completed: 20220302 Latest Revision: 20220302
Update Code:: 20240105
DOI:: 10.1007/s12031-021-01823-9
PMID:: 33738762
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Apoptosis of hippocampal neurons is one of the mechanisms of hippocampal atrophy in posttraumatic stress disorder (PTSD), and it is also an important cause of memory impairment in PTSD patients. Endoplasmic reticulum stress (ERS) mediated by activated transcription factor 6α (ATF6α)/site 1 protease (S1P)/S2P is involved in cell apoptosis, but it is not clear whether it is involved in hippocampal neuron apoptosis caused by PTSD. A PTSD rat model was constructed by the single prolonged stress (SPS) method. The study was divided into three parts. Experiment 1 included the control group, SPS 1 d group, SPS 7 d group, and SPS 14 d group. Experiment 2 included the control group, SPS 7 d group, SPS 7 d + AEBSF group, and control + AEBSF group. (4-(2-Aminoethyl)benzenesulfonyl fluoride hydrochloride (AEBSF) is an ATF6α pathway inhibitor). Experiment 3 included the control group, SPS 4 d group, SPS 4 d + AEBSF group, and control + AEBSF group. The protein and mRNA expression levels of ATF6α, glucose-regulated protein (GRP78), S1P, S2P, C/EBP homologous protein (CHOP), and caspase-12 in the hippocampus of PTSD rats were detected by immunohistochemistry, Western blotting and qRT-PCR. Apoptosis of hippocampal neurons was detected by TUNEL staining. In experiment 1, the protein and mRNA expression of ATF6α and GRP78 increased gradually in the SPS 1 d group and the SPS 7 d group but decreased in the SPS 14 d group (P < 0.01). In experiment 2, compared with that in the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were significantly increased in the SPS 7 d group (P < 0.01). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were significantly decreased after AEBSF pretreatment (P < 0.01). In experiment 3, compared with that in the control group, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were increased in the SPS 14 d group (P < 0.05). However, the protein and mRNA expression of ATF6α, GRP78, S1P, S2P, CHOP, and caspase-12 and the apoptosis rate were decreased after AEBSF pretreatment (P < 0.05). SPS induced apoptosis of hippocampal neurons by activating ERS mediated by ATF6α, suggesting that ERS-induced apoptosis is involved in the occurrence of PTSD.
(© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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