Analyze Mouse Knockout Models of UPR Pathway Elements

2022 ◽  
pp. 205-219
Author(s):  
Chao Zheng ◽  
Cheng Wang ◽  
Qiang Jie ◽  
Liu Yang
Keyword(s):  
Mouse Knockout ◽  
Upr Pathway

scholarly journals Protease Inhibitor Anti-HIV, Lopinavir, Impairs Placental Endocrine Function

2021 ◽  
Vol 22 (2) ◽  
pp. 683
Author(s):  
Camille Fraichard ◽  
Fidéline Bonnet-Serrano ◽  
Christelle Laguillier-Morizot ◽  
Marylise Hebert-Schuster ◽  
René Lai-Kuen ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Metastatic Lymph Node ◽  
Endocrine Function ◽  
Maternal Circulation ◽  
Hormone Production ◽  
Mitofusin 2 ◽  
Villous Trophoblast ◽  
Activating Transcription Factor ◽  
Upr Pathway

Protease Inhibitors (PI e.g., ritonavir (RTV) and lopinavir (LPV)) used to treat pregnant mothers infected by HIV induce prematurity and endocrine dysfunctions. The maintenance of pregnancy relies on placental hormone production (human Chorionic Gonadotrophin (hCG) and progesterone (P4)). Those functions are ensured by the villous trophoblast and are mainly regulated by the Unfolded Protein Response (UPR) pathway and mitochondria. We investigated, in vitro, if PI impair hCG and P4 production and the potential intracellular mechanisms involved. Term villous cytotrophoblast (VCT) were cultured with or without RTV or LPV from 6 to 48 h. VCT differentiation into syncytiotrophoblast (ST) was followed measuring hCG and P4 secretion. We evaluated the expression of P4 synthesis partners (Metastatic Lymph Node 64 (MLN64), cholesterol side-chain cleavage (P450SCC), Hydroxy-delta-5-Steroid Dehydrogenase and 3 Beta-and steroid delta-isomerase 1 (HSD3B1)), of mitochondrial pro-fusion factors (Mitofusin 2 (Mfn2), Optic Atrophy 1 (OPA1)) and of UPR factors (Glucose-Regulated Protein 78 (GRP78), Activating Transcription Factor 4 (ATF4), Activating Transcription Factor 6 (ATF6), spliced X-box Binding Protein 1 (sXBP1)). RTV had no significant effect on hCG and P4 secretion, whereas lopinavir significantly decreased both secretions. LPV also decreased P450SCC and HSD3B1 expression, whereas it increased Mfn2, GRP78 and sXBP1 expression in ST. RTV has no effect on the endocrine placenta. LPV impairs both villous trophoblast differentiation and P4 production. It is likely to act via mitochondrial fusion and UPR pathway activation. These trophoblastic alterations may end in decreased P4 levels in maternal circulation, inducing prematurity.

scholarly journals Dysregulation in the Unfolded Protein Response in the FGR Rat Pancreas

2020 ◽  
Vol 2020 ◽  
pp. 1-11 ◽  
Author(s):  
Xiaomei Liu ◽  
Yanyan Guo ◽  
Jun Wang ◽  
Liangliang Zhu ◽  
Linlin Gao
Keyword(s):  
Protein Kinase ◽  
Unfolded Protein Response ◽  
Binding Protein ◽  
Protein Kinase R ◽  
Pregnant Rats ◽  
Fetal Pancreas ◽  
Unfolded Protein ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

Accumulating evidence suggests that fetal growth restriction (FGR) leads to the development of diabetes mellitus in adults. The aim of this study was to investigate the effect of protein malnutrition in utero on the pancreatic unfolded protein response (UPR) pathway in FGR offspring. An FGR model was developed by feeding a low-protein diet to pregnant rats throughout gestation. Eighty-four UPR pathway components in the pancreas were investigated by quantitative PCR arrays and confirmed by qPCR and western blotting. Activating transcription factor (Atf4 and Atf6), herpud1, protein kinase R-like endoplasmic reticulum kinase (Perk), X-box binding protein 1 (Xbp1), and the phosphorylation of eIF2α were upregulated, while cyclic AMP-responsive element-binding protein 3-like protein was markedly downregulated in FGR fetuses compared with controls. Investigation in adult offspring revealed temporal changes, for most UPR factors restored to normal, except that dysregulation of Atf6 and Creb3l3 maintained until adulthood. Moreover, autophagy was suppressed in FGR fetal pancreas and may be associated with decreased activation of AMP-activated protein kinase (Ampk). Apoptosis regulators Bax and cleaved-caspase 3 and 9 were upregulated in FGR fetal pancreas. Given that islet size and number were decreased in FGR fetus, we speculated that the aberrant intrauterine milieu impaired UPR signaling in fetal pancreas development. Whether these alterations early in life contribute to the predisposition of FGR fetuses to adult metabolic disorders invites further exploration.

scholarly journals Initial characterization of behavior and ketamine response in a mouse knockout of the post-synaptic effector gene Anks1b

2017 ◽  
Vol 641 ◽  
pp. 26-32 ◽  
Author(s):  
Rachel M. Enga ◽  
Ann C. Rice ◽  
Pamela Weller ◽  
Mark A. Subler ◽  
Daiyoon Lee ◽  
...  
Keyword(s):  
Effector Gene ◽  
Mouse Knockout ◽  
Initial Characterization

scholarly journals Optical manipulation ofSaccharomyces cerevisiaecells reveals that green light protection against UV irradiation is favored by low Ca2+and requires intact UPR pathway

FEBS Letters ◽  
2013 ◽  
Vol 587 (21) ◽  
pp. 3514-3521 ◽  
Author(s):  
Ileana C. Farcasanu ◽  
Radu Mitrica ◽  
Ligia Cristache ◽  
Ioana Nicolau ◽  
Lavinia L. Ruta ◽  
...  
Keyword(s):  
Uv Irradiation ◽  
Green Light ◽  
Optical Manipulation ◽  
Light Protection ◽  
Upr Pathway

scholarly journals Multiple Myeloma-Derived Extracellular Vesicles Induce Osteoclastogenesis through the Activation of the XBP1/IRE1α Axis

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2167 ◽  
Author(s):  
Lavinia Raimondi ◽  
Angela De Luca ◽  
Simona Fontana ◽  
Nicola Amodio ◽  
Viviana Costa ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Endoplasmic Reticulum ◽  
Extracellular Vesicle ◽  
Scientific Data ◽  
Daily Experience ◽  
Unfolded Protein ◽  
Xbp1 Mrna ◽  
Protein Response ◽  
Upr Pathway

Bone disease severely affects the quality of life of over 70% of multiple myeloma (MM) patients, which daily experience pain, pathological fractures, mobility issues and an increased mortality. Recent data have highlighted the crucial role of the endoplasmic reticulum-associated unfolded protein response (UPR) in malignant transformation and tumor progression; therefore, targeting of UPR-related molecules may open novel therapeutic avenues. Endoplasmic reticulum (ER) stress and UPR pathways are constitutively activated in MM cells, which are characterized by an increased protein turnover as a consequence of high production of immunoglobulins and high rates of protein synthesis. A great deal of scientific data also evidenced that a mild activation of UPR pathway can regulate cellular differentiation. Our previous studies revealed that MM cell-derived small extracellular vesicle (MM-EV) modulated osteoclasts (OCs) function and induced OCs differentiation. Here, we investigated the role of the UPR pathway, and in particular of the IRE1α/XBP1 axis, in osteoclastogenesis induced by MM-EVs. By proteomic analysis, we identified UPR signaling molecules as novel MM-EV cargo, prompting us to evaluate the effects of the MM-EVs on osteoclastogenesis through UPR pathway. MM-EVs administration in a murine macrophage cell line rapidly induced activation of IRE1α by phosphorylation in S724; accordingly, Xbp1 mRNA splicing was increased and the transcription of NFATc1, a master transcription factor for OCs differentiation, was activated. Some of these results were also validated using both human primary OC cultures and MM-EVs from MM patients. Notably, a chemical inhibitor of IRE1α (GSK2850163) counteracted MM-EV-triggered OC differentiation, hampering the terminal stages of OCs differentiation and reducing bone resorption.

scholarly journals Robust and Sensitive Analysis of Mouse Knockout Phenotypes

PLoS ONE ◽  
2012 ◽  
Vol 7 (12) ◽  
pp. e52410 ◽  
Author(s):  
Natasha A. Karp ◽  
David Melvin ◽  
Richard F. Mott ◽  
Keyword(s):  
Sensitive Analysis ◽  
Mouse Knockout

scholarly journals Mouse Knockout of the Cholesterogenic Cytochrome P450 Lanosterol 14α-Demethylase (Cyp51) Resembles Antley-Bixler Syndrome

2011 ◽  
Vol 286 (33) ◽  
pp. 29086-29097 ◽  
Author(s):  
Rok Keber ◽  
Helena Motaln ◽  
Kay D. Wagner ◽  
Nataša Debeljak ◽  
Minoo Rassoulzadegan ◽  
...  
Keyword(s):  
Cytochrome P450 ◽  
Mouse Knockout

scholarly journals Evaluation of the role of IKAChin atrial fibrillation using a mouse knockout model

2001 ◽  
Vol 37 (8) ◽  
pp. 2136-2143 ◽  
Author(s):  
Pramesh Kovoor ◽  
Kevin Wickman ◽  
Colin T Maguire ◽  
William Pu ◽  
Josef Gehrmann ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Mouse Knockout ◽  
Knockout Model

scholarly journals A novel role in cytokinesis reveals a housekeeping function for the unfolded protein response

2007 ◽  
Vol 177 (6) ◽  
pp. 1017-1027 ◽  
Author(s):  
Alicia A. Bicknell ◽  
Anna Babour ◽  
Christine M. Federovitch ◽  
Maho Niwa
Keyword(s):  
Cell Cycle ◽  
Unfolded Protein Response ◽  
Normal Cell ◽  
Growth Conditions ◽  
Unfolded Protein ◽  
Functional Capabilities ◽  
Cellular Events ◽  
The Unfolded Protein Response ◽  
Protein Response ◽  
Upr Pathway

The unfolded protein response (UPR) pathway helps cells cope with endoplasmic reticulum (ER) stress by activating genes that increase the ER's functional capabilities. We have identified a novel role for the UPR pathway in facilitating budding yeast cytokinesis. Although other cell cycle events are unaffected by conditions that disrupt ER function, cytokinesis is sensitive to these conditions. Moreover, efficient cytokinesis requires the UPR pathway even during unstressed growth conditions. UPR-deficient cells are defective in cytokinesis, and cytokinesis mutants activate the UPR. The UPR likely achieves its role in cytokinesis by sensing small changes in ER load and making according changes in ER capacity. We propose that cytokinesis is one of many cellular events that require a subtle increase in ER function and that the UPR pathway has a previously uncharacterized housekeeping role in maintaining ER plasticity during normal cell growth.

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