title: Nitric Oxide and Protein Disulfide Isomerase Explain the Complexities of Unfolded Protein Response Following Intra-hippocampal Aβ Injection.
abstract: Several pathways involved in regulation of intracellular protein integrity are known as the protein quality control (PQC) system. Molecular chaperones as the main players are engaged in various aspects of PQC system. According to the importance of these proteins in cell survival, in the present study, we traced endoplasmic reticulum-specific markers and chaperone-mediated autophagy (CMA)-associated factors as two main arms of PQC system in intra-hippocampal amyloid beta (Aβ)-injected rats during 10 days running. Data analysis from Western blot indicated that exposure to Aβ activates immunoglobulin heavy-chain-binding protein (Bip) which is the upstream regulator of unfolded protein responses (UPR). Activation of UPR system eventually led to induction of pro-apoptotic factors like CHOP, calpain, and caspase-12. Moreover, our data revealed that protein disulfide isomerase activity dramatically decreased after Aβ injection, which could be attributed to the increased levels of nitric oxide. Besides, Aβ injection induced levels of 2 members of heat shock proteins (Hsp) 70 and 90. Elevated levels of Hsps family members are accompanied by increased levels of lysosome-associated membrane protein type-2A (Lamp-2A) that are involved in CMA. Despite the reduction in CHOP, calpain, caspase-12, and Lamp-2A protein levels, the levels of molecular chaperones Bip, Hsps70, and 90 increased 10 days after Aβ injection in comparison to the control group. Based on our results, 10 days after Aβ injection, despite the activation of protective chaperones, markers associated with neurotoxicity were still elevated.
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fariba
authors.initials: F
authors.lastname: Khodagholi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Hadi
authors.initials: H
authors.lastname: Digaleh
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Fereshteh
authors.initials: F
authors.lastname: Motamedi
authors.affiliation: NeuroBiology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.|Neuroscience Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Forough
authors.initials: F
authors.lastname: Foolad
authors.affiliation: Department of Physiology, Faculty of Medicine, Hormozgan University of Medical Sciences, Bandar Abbas, Iran. fatima.shaerzadeh@gmail.com.
authors.forename: Fatemeh
authors.initials: F
authors.lastname: Shaerzadeh
mesh_terms: D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D019704:Protein Disulfide-Isomerases / Q000378:metabolism*; D058767:Protein Unfolding; D017208:Rats, Wistar
chemical_list: D016229:Amyloid beta-Peptides; D009569:Nitric Oxide; D019704:Protein Disulfide-Isomerases
keywords: Alzheimer’s disease; Bip; Chaperones; Heat shock proteins; Nitric oxide; Protein disulfide isomerase