Profile of the unfolded protein response in rat cerebellar cortical development

Naughton, Michelle; McMahon, Jill; Healy, Sinéad; FitzGerald, Una

doi:10.1002/cne.24718

Cited by 6 publications

(5 citation statements)

References 35 publications

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“…eIF2a is involved in the PERK signalling pathway and is an upstream molecule of CHOP [21]. Glucose regulated protein 94 (GRP94) is a downstream target of ATF6 and could reflect the level of ER stress to some extent [22]. In our study, increased p-eIF2a, ATF-6 and CHOP implied that excessive ERstress might activate the pro-apoptosis pathway induced by CHOP.…”

Section: Effect Of Honokiol Treatment On Inos Enos and Vegf Levels Imentioning

confidence: 58%

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

Wei

Liu

Ying

et al. 2020

Biotechnology & Biotechnological Equipment

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The levels of inflammatory factors in pregnancy-induced hypertension (PIH) are closely correlated with the severity of the disease. The enhanced endoplasmic reticulum (ER) stress response and upregulated iNOS might contribute to the pathophysiology of preeclampsia. Honokiol has been shown to be a potential anti-inflammatory and anti-ER stress agent. However, the effect of honokiol on the inflammation and ER stress has not been investigated in a gestational hypertensive model. The present study aimed to elucidate the role of honokiol in inflammation, ER stress and endothelial/inducible nitric oxide synthase (eNOS/iNOS) in a PIH rat model. Rats with hypoxia-induced PIH were administered honokiol (0, 200, 600, 2000 lg/kg) daily for one week to different groups by intragastric administration. Systolic blood pressure (SBP) and urinary protein concentration were measured via the tail-cuff method and CBB kit. Proinflammatory cytokines and ER-stress markers, VEGF, NO, iNOS and eNOS in the plasma or placental tissue were analyzed by enzyme-linked immunosorbent assay (ELISA), quantitative real time polymerase chain reaction (RT-qPCR), NO assay kit or western blot. The blood pressure and urinary protein level in PIH rats were significantly decreased after honokiol. Honokiol significantly inhibited the elevated levels of proinflammatory cytokines and ER-stress markers, which were accompanied by the upregulation of eNOS, NO and VEGF mRNA in PIH rats. However, the level of iNOS was reduced by honokiol. Our study suggests a beneficial potential of honokiol in PIH rats through inhibition of proinflammatory cytokines and ER stress. Honokiol could be an intriguing therapeutic approach in ER stress related PIH.

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Section: Effect Of Honokiol Treatment On Inos Enos and Vegf Levels Imentioning

confidence: 58%

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

Wei

Liu

Ying

et al. 2020

Biotechnology & Biotechnological Equipment

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“…PDI is an enzyme to help protein folding by catalyzing the oxidation, reduction, and isomerization of the disulfide bonds of misfolded or nascent proteins. UPR is necessary for the normal development of cortical neurons and cerebellar white matter (Naughton et al, 2019). It protects neuron cells against ER stress induced by the accumulation of misfolded proteins (Naughton et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

“…UPR is necessary for the normal development of cortical neurons and cerebellar white matter (Naughton et al, 2019). It protects neuron cells against ER stress induced by the accumulation of misfolded proteins (Naughton et al, 2019). PDI is one of the critical factors in UPR, and its dysfunction causes the accumulation of unfolded/misfolded proteins in neuronal cells and neurodegeneration.…”

Section: Discussionmentioning

confidence: 99%

Bisphenol A and rotenone induce S-nitrosylation of protein disulfide isomerase (PDI) and inhibit neurite outgrowth of primary cultured cells of the rat hippocampus and PC12 cells

et al. 2020

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-Bisphenol A (BPA) interferes the function and development of the central nervous system (CNS), resulting in behavioral abnormalities and memory loss. S-nitrosylation of protein disulfide isomerase (PDI) is increased in brains with sporadic Alzheimer's disease and Parkinson's disease. The aim of the present study was to clarify the role of nitric oxide (NO) in BPA-induced neurotoxicity. Since rotenone induces NO-mediated neurodegeneration through S-nitrosylation of PDI, it was used as a positive control. First, rats were treated with BPA and rotenone, and S-nitrosylation of PDI was detected in rat brain microsomes. BPA and rotenone decreased RNase oxidation activity of PDI concomitant with S-nitrosylation of PDI. Next, to clarify S-nitrosylation of PDI by BPA and rotenone in rat brains, we treated the rat pheochromocytoma cell line PC12 and primary cultured neuron cells from the rat hippocampus with BPA (5 and 10 μM) and rotenone (100 or 200 nM). BPA induced S-nitrosylation of PDI, while NG-monomethyl-L-arginine (L-NMMA), a NOS inhibitor, exerted the opposite effects. Finally, to evaluate the toxicity of BPA in the CNS, we investigated its effects on neurite outgrowth of PC12 and primary cultured neuron cells. BPA inhibited neurite outgrowth of these cells, while L-NMMA reversed this inhibition. The involvement of PDI activity in neurite outgrowth was also examined, and bacitracin, a PDI inhibitor, is shown to decrease neurite outgrowth. Furthermore, the overexpression of PDI, but not a catalytically inactive PDI mutant, enhanced neurite outgrowth. These results suggested that S-nitrosylation of PDI induced by excessive NO caused BPA-induced neurotoxicity.

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“…Finally, it is of interest that when the expression of ER stress sensors and their downstream targets in the developing cerebellar cortex was analyzed using immunocytochemistry in histological sections, the activation of PERK and IRE1 was observed in normally developing CGC precursors [ 237 ]. A second proliferative pPERK-positive population was also detected in the internal granular layer, and, in general, the density of UPR protein-positive cells was found to decrease significantly when profiles in early and late postnatal ages were compared.…”

Section: The Cerebellar Granule Cells (Cgcs) As a Model To Study The ...mentioning

confidence: 99%

Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death

Merighi

Lossi

2022

IJMS

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Besides protein processing, the endoplasmic reticulum (ER) has several other functions such as lipid synthesis, the transfer of molecules to other cellular compartments, and the regulation of Ca2+ homeostasis. Before leaving the organelle, proteins must be folded and post-translationally modified. Protein folding and revision require molecular chaperones and a favorable ER environment. When in stressful situations, ER luminal conditions or chaperone capacity are altered, and the cell activates signaling cascades to restore a favorable folding environment triggering the so-called unfolded protein response (UPR) that can lead to autophagy to preserve cell integrity. However, when the UPR is disrupted or insufficient, cell death occurs. This review examines the links between UPR signaling, cell-protective responses, and death following ER stress with a particular focus on those mechanisms that operate in neurons.

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Profile of the unfolded protein response in rat cerebellar cortical development

Cited by 6 publications

References 35 publications

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

Honokiol inhibits inflammation and endoplasmic reticulum stress in a rat model of pregnancy-induced hypertension

Bisphenol A and rotenone induce S-nitrosylation of protein disulfide isomerase (PDI) and inhibit neurite outgrowth of primary cultured cells of the rat hippocampus and PC12 cells

Endoplasmic Reticulum Stress Signaling and Neuronal Cell Death

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