keyword
https://read.qxmd.com/read/38433101/to-initiate-or-not-to-initiate-a-critical-assessment-of-eif2a-eif2d-and-mct-1%C3%A2-denr-to-deliver-initiator-trna-to-ribosomes
#1
REVIEW
Daisy J Grove, Paul J Russell, Michael G Kearse
Selection of the correct start codon is critical for high-fidelity protein synthesis. In eukaryotes, this is typically governed by a multitude of initiation factors (eIFs), including eIF2·GTP that directly delivers the initiator tRNA (Met-tRNAi Met ) to the P site of the ribosome. However, numerous reports, some dating back to the early 1970s, have described other initiation factors having high affinity for the initiator tRNA and the ability of delivering it to the ribosome, which has provided a foundation for further work demonstrating non-canonical initiation mechanisms using alternative initiation factors...
2024: Wiley Interdisciplinary Reviews. RNA
https://read.qxmd.com/read/38376197/activation-of-protein-kinase-receptor-pkr-plays-a-pro-viral-role-in-mammarenavirus-infected-cells
#2
JOURNAL ARTICLE
Haydar Witwit, Roaa Khafaji, Arul Salaniwal, Arthur S Kim, Beatrice Cubitt, Nathaniel Jackson, Chengjin Ye, Susan R Weiss, Luis Martinez-Sobrido, Juan Carlos de la Torre
Many viruses, including mammarenaviruses, have evolved mechanisms to counteract different components of the host cell innate immunity, which is required to facilitate robust virus multiplication. The double-stranded RNA (dsRNA) sensor protein kinase receptor (PKR) pathway plays a critical role in the cell anti-viral response. Whether PKR can restrict the multiplication of the Old World mammarenavirus lymphocytic choriomeningitis virus (LCMV) and the mechanisms by which LCMV may counteract the anti-viral functions of PKR have not yet been investigated...
February 20, 2024: Journal of Virology
https://read.qxmd.com/read/38266075/yeast-eif2a-has-a-minimal-role-in-translation-initiation-and-uorf-mediated-translational-control-in-vivo
#3
JOURNAL ARTICLE
Swati Gaikwad, Fardin Ghobakhlou, Hongen Zhang, Alan G Hinnebusch
Initiating translation of most eukaryotic mRNAs depends on recruitment of methionyl initiator tRNA (Met-tRNAi) in a ternary complex (TC) with GTP-bound eukaryotic initiation factor 2 (eIF2) to the small (40S) ribosomal subunit, forming a 43S preinitiation complex (PIC) that attaches to the mRNA and scans the 5'-untranslated region (5' UTR) for an AUG start codon. Previous studies have implicated mammalian eIF2A in GTP-independent binding of Met-tRNAi to the 40S subunit and its recruitment to specialized mRNAs that do not require scanning, and in initiation at non-AUG start codons, when eIF2 function is attenuated by phosphorylation of its α-subunit during stress...
January 24, 2024: ELife
https://read.qxmd.com/read/38205251/undersized-telomeres-in-regulatory-t%C3%A2-cells-link-to-the-pathogenesis-of-allergic-rhinitis
#4
JOURNAL ARTICLE
Jinmei Xue, Zhizhen Liu, Yun Liao, Xiwen Zhang, Yu Liu, Lihua Mo, Rui Dong, Qiang Li, Xizhuo Sun, Jun Xie, Pingchang Yang
Telomeres are an important biomarker in the cell destiny. The relationship between telomeres and regulatory T cells (Tregs) has not yet been investigated. The objective of this study is to evaluate the link between Tregs' telomere length and allergic rhinitis (AR)'s pathogenesis. Here, we report that low telomerase activity and high endoplasmic reticulum stress status were observed in Tregs from AR patients, as shown in the results. Immune regulatory molecules levels were correlated with the length of Tregs' telomeres...
January 19, 2024: IScience
https://read.qxmd.com/read/38187690/unveiling-the-intercompartmental-signaling-axis-mitochondrial-to-er-stress-response-mersr-and-its-impact-on-proteostasis
#5
Jeson J Li, Nan Xin, Chunxia Yang, Larissa A Tavizon, Ruth Hong, Travis I Moore, Rebecca George Tharyan, Adam Antebi, Hyun-Eui Kim
Maintaining protein homeostasis is essential for cellular health. During times of proteotoxic stress, cells deploy unique defense mechanisms to achieve resolution. Our previous research uncovered a cross-compartmental Mitochondrial to Cytosolic Stress Response (MCSR), a unique stress response activated by the perturbation of mitochondrial proteostasis, which ultimately results in the improvement of proteostasis in the cytosol. Here, we found that this signaling axis also influences the unfolded protein response of the endoplasmic reticulum (UPR ER ), suggesting the presence of a Mitochondria to ER Stress Response (MERSR)...
December 21, 2023: bioRxiv
https://read.qxmd.com/read/38187575/diroximel-fumarate-acts-through-nrf2-to-attenuate-methylglyoxal-induced-nociception-in-mice-and-decreases-isr-activation-in-drg-neurons
#6
Muhammad Saad Yousuf, Marisol Mancilla Moreno, Jiahe Li, Lucy He, Danielle Royer, Jennifer Zhang, Brodie J Woodall, Peter M Grace, Theodore J Price
UNLABELLED: Diabetic neuropathic pain is associated with elevated plasma levels of methylglyoxal (MGO). MGO is a metabolite of glycolysis that causes mechanical hypersensitivity in mice by inducing the integrated stress response (ISR), which is characterized by phosphorylation of eukaryotic initiation factor 2α (p-eIF2α). Nuclear factor erythroid 2-related factor 2 (Nrf2) is a transcription factor that regulates the expression of antioxidant proteins that neutralize MGO. We hypothesized that activating Nrf2 using diroximel fumarate (DRF) would alleviate MGO-induced pain hypersensitivity...
December 23, 2023: bioRxiv
https://read.qxmd.com/read/38150547/hemopexin-reverses-activation-of-lung-eif2a-and-decreases-mitochondrial-injury-in-chlorine-exposed-mice
#7
JOURNAL ARTICLE
Sadis Matalon, Zhihong Yu, Shubham Dubey, Israr Ahmad, Emily M Stephens, Ammar Saadoon Alishlash, Ashley Meyers, Douglas Cossar, Donald Stewart, Edward P Acosta, Kyoko Kojima, Tamas Jilling, James A Mobley
We assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl2 ) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult male and female C57BL/6 mice to Cl2 (500 ppm for 30 min), returned them to room air, and injected them intramuscularly with either human hemopexin (hHPX; 5 µg/ g BW in 50 µl saline) or vehicle at 1h post exposure. Upon return to room air, Cl2 exposed mice, injected with vehicle, developed respiratory acidosis, increased concentrations of plasma proteins in the alveolar space, lung mitochondrial DNA injury, increased levels of free plasma heme and major alterations of their lung proteome...
December 27, 2023: American Journal of Physiology. Lung Cellular and Molecular Physiology
https://read.qxmd.com/read/38129650/reconstitution-of-c9orf72-ggggcc-repeat-associated-non-aug-translation-with-purified-human-translation-factors
#8
JOURNAL ARTICLE
Hayato Ito, Kodai Machida, Mayuka Hasumi, Morio Ueyama, Yoshitaka Nagai, Hiroaki Imataka, Hideki Taguchi
Nucleotide repeat expansion of GGGGCC (G4 C2 ) in the non-coding region of C9orf72 is the most common genetic cause underlying amyotrophic lateral sclerosis and frontotemporal dementia. Transcripts harboring this repeat expansion undergo the translation of dipeptide repeats via a non-canonical process known as repeat-associated non-AUG (RAN) translation. In order to ascertain the essential components required for RAN translation, we successfully recapitulated G4 C2 -RAN translation using an in vitro reconstituted translation system comprising human factors, namely the human PURE system...
December 20, 2023: Scientific Reports
https://read.qxmd.com/read/38064788/ochratoxin-a-triggers-endoplasmic-reticulum-stress-through-perk-nrf2-signaling-and-dna-damage-during-early-embryonic-developmental-competence-in-pigs
#9
JOURNAL ARTICLE
Seong-Min Woo, Seul-Gi Yang, Ye-Won Kim, Deog-Bon Koo, Hyo-Jin Park
Ochratoxin A (OTA), a mycotoxin found in foods, has a deleterious effect on female reproduction owing to its endocrine-disrupting activity mediated through endoplasmic reticulum (ER) stress and reactive oxygen species (ROS) production. However, the mechanisms of OTA-induced ER stress in pig embryos during in vitro culture (IVC) are not yet fully understood. In the present study, porcine embryos were cultured for two days in an IVC medium supplemented with 0.5, 1.0, and 5.0 μM OTA, which led to an OTA-induced reduction in the developmental rate of blastocysts...
December 7, 2023: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/38056196/modulating-endoplasmic-reticulum-stress-attenuates-mast-cell-degranulation
#10
JOURNAL ARTICLE
Jialiang Fan, Longpeng Ma, Bailing Xie, Shuyao Qiu, Shuo Song, Zhiyuan Tang, Yongjin Wu, Hui Huangfu, Yan Feng, Xiangqian Luo, Pingchang Yang
OBJECTIVES: Degranulation of mast cells leads to direct allergic symptoms. The underlying mechanism needs to be explored further. Endoplasmic reticulum (ER) stress is involved in the pathogenesis of allergic conditions. The objective of this study is to gain a better understanding of the mechanism of mast cell degranulation. METHODS: Bone marrow derived mast cells and mast cells isolated from the airway tissues were prepared. The role of ER stress in mediating the release of mast cells was tested...
December 5, 2023: International Immunopharmacology
https://read.qxmd.com/read/38056121/hesperetin-protects-hippocampal-neurons-from-the-neurotoxicity-of-aflatoxin-b1-in-mice
#11
JOURNAL ARTICLE
Chao Song, Zixu Wang, Jing Cao, Yulan Dong, Yaoxing Chen
Aflatoxin B1 (AFB1) is a major food and feed pollutant that endangers public health. Previous studies have shown that exposure to AFB1 causes neurotoxicity in the body. However, the mechanism of neurotoxicity caused by AFB1 is not well understood, and finding a workable and practical method to safeguard animals from AFB1 toxicity is essential. This study confirmed that AFB1 caused endoplasmic reticulum stress (ER stress) and apoptosis in hippocampal neurons using C57BL/6 J mice and HT22 cells as models...
December 5, 2023: Ecotoxicology and Environmental Safety
https://read.qxmd.com/read/38011112/eif2a-represses-cell-wall-biogenesis-gene-expression-in-saccharomyces-cerevisiae
#12
JOURNAL ARTICLE
Laura Meyer, Baptiste Courtin, Maïté Gomard, Abdelkader Namane, Emmanuelle Permal, Gwenael Badis, Alain Jacquier, Micheline Fromont-Racine
Translation initiation is a complex and highly regulated process that represents an important mechanism, controlling gene expression. eIF2A was proposed as an alternative initiation factor, however, its role and biological targets remain to be discovered. To further gain insight into the function of eIF2A in Saccharomyces cerevisiae, we identified mRNAs associated with the eIF2A complex and showed that 24% of the most enriched mRNAs encode proteins related to cell wall biogenesis and maintenance. In agreement with this result, we showed that an eIF2A deletion sensitized cells to cell wall damage induced by calcofluor white...
2023: PloS One
https://read.qxmd.com/read/37999823/semaphorin-3%C3%A2-a-restores-the-ability-of-type-1-regulatory-t-cells-to-suppress-food-allergy
#13
JOURNAL ARTICLE
Panpan Gao, Shuo Song, Yanan Wang, Huazhen Liu, Xiangyu Wang, Qing Shu, Pingchang Yang, Pengyuan Zheng
Food allergy (FA) is a common immune disorder that involves dysfunctional immune regulation. More remedies for restoring immune regulation are necessary. Semaphorin 3 A (Sema3a) is a secreted protein of the semaphorin family, which plays a role in immune responses at all stages. The objective of this study is to gain an understanding of how Sema3a can restore the immune regulatory abilities of type 1 regulatory T cells (Tr1 cells). In this study, blood samples were taken from patients with FA. Tr1 cells were purified from blood samples using flow cytometry cell sorting, using LAG3 and CD49b as surface markers...
November 24, 2023: Immunologic Research
https://read.qxmd.com/read/37986989/yeast-eif2a-has-a-minimal-role-in-translation-initiation-and-uorf-mediated-translational-control-in-vivo
#14
Swati Gaikwad, Fardin Ghobakhlou, Hongen Zhang, Alan G Hinnebusch
Initiating translation of most eukaryotic mRNAs depends on recruitment of methionyl initiator tRNA (Met- tRNAi) in a ternary complex (TC) with GTP-bound eukaryotic initiation factor 2 (eIF2) to the small (40S) ribosomal subunit, forming a 43S preinitiation complex (PIC) that attaches to the mRNA and scans the 5'- untranslated region (5' UTR) for an AUG start codon. Previous studies have implicated mammalian eIF2A in GTP-independent binding of Met-tRNAi to the 40S subunit and its recruitment to specialized mRNAs that do not require scanning, and in initiation at non-AUG start codons, when eIF2 function is attenuated by phosphorylation of its α-subunit during stress...
October 8, 2023: bioRxiv
https://read.qxmd.com/read/37942317/acriflavine-a-hif-1-inhibitor-preserves-vision-in-an-experimental-autoimmune-encephalomyelitis-model-of-optic-neuritis
#15
JOURNAL ARTICLE
Jeffrey J Anders, Benjamin W Elwood, Randy H Kardon, Oliver W Gramlich
INTRODUCTION: Optic neuritis (ON) is often an early sign of multiple sclerosis (MS), and recent studies show a link between HIF-1 pathway activation and inflammation. This study aimed to determine if inhibition of the HIF-1 pathway using the HIF-1a antagonist acriflavine (ACF) can reduce clinical progression and rescue the ocular phenotype in an experimental autoimmune encephalomyelitis (EAE) ON model. METHODS: EAE-related ON was induced in 60 female C57BL/6J mice by immunization with MOG33-55, and 20 EAE mice received daily systemic injections of ACF at 5 mg/kg...
2023: Frontiers in Immunology
https://read.qxmd.com/read/37891939/dietary-betaine-attenuates-high-carbohydrate-diet-induced-oxidative-stress-endoplasmic-reticulum-stress-and-apoptosis-in-mandarin-fish-siniperca-chuatsi
#16
JOURNAL ARTICLE
Hongyan Li, Yanzhi Zeng, Xinyu Zheng, Guangjun Wang, Jingjing Tian, Wangbao Gong, Yun Xia, Kai Zhang, Zhifei Li, Wenping Xie, Jun Xie, Ermeng Yu
To investigate the impact of betaine on high-carbohydrate-diet-induced oxidative stress and endoplasmic reticulum (ER) stress, mandarin fish ( Siniperca chuatsi ) (23.73 ± 0.05 g) were fed with control (NC), betaine (BET), high carbohydrate (HC), and high carbohydrate + betaine (HC + BET) diets for 8 weeks. The results showed that betaine significantly promoted the growth of mandarin fish irrespective of the dietary carbohydrate levels. The HC diet induced oxidative stress, as evidenced by significantly elevated MDA levels...
October 13, 2023: Antioxidants (Basel, Switzerland)
https://read.qxmd.com/read/37697311/sex-hormone-binding-globulin-shbg-mitigates-er-stress-and-improves-viability-and-insulin-sensitivity-in-adipose-derived-mesenchymal-stem-cells-asc-of-equine-metabolic-syndrome-ems-affected-horses
#17
JOURNAL ARTICLE
Nabila Bourebaba, Mateusz Sikora, Badr Qasem, Lynda Bourebaba, Krzysztof Marycz
BACKGROUND: Equine metabolic syndrome (EMS), which encompasses insulin resistance, low-grade inflammation and predisposition to laminitis is a critical endocrine disorder among the most prevalent conditions affecting horses from different breeds. According to the most recent research, low human sex hormone-binding globulin (SHBG) serum levels correlate with an increased risk of obesity, insulin resistance and diabetes, and may contribute to overall metabolic dysregulations. This study aimed to test whether exogenous SHBG could protect EMS affected adipose-derived stromal stem cells (EqASCEMS ) from apoptosis, oxidative stress, ER stress and thus improve insulin sensitivity...
September 11, 2023: Cell Communication and Signaling: CCS
https://read.qxmd.com/read/37645744/hemopexin-reverses-activation-of-lung-eif2a-and-decreases-mitochondrial-injury-in-chlorine-exposed-mice
#18
Sadis Matalon, Zhihong Yu, Shubham Dubey, Israr Ahmad, Emily M Stephens, Ammar Saadoon Alishlash, Ashley Meyers, Douglas Cossar, Donald Stewart, Edward P Acosta, Kyoko Kojima, Tamas Jilling, James A Mobley
We assessed the mechanisms by which non-encapsulated heme, released in the plasma of mice post exposure to chlorine (Cl 2 ) gas, resulted in the initiation and propagation of acute lung injury. We exposed adult C57BL/6 male and female to Cl 2 (500 ppm for 30 min) in environmental chambers and returned them to room air and injected them intramuscularly with a single dose of human hemopexin (hHPX; 5 µg/ g BW), the most efficient scavenger of heme, 30-60 min post exposure. Concentrations of hHPX in plasma of air and Cl 2 exposed mice were 9081±900 vs...
August 19, 2023: bioRxiv
https://read.qxmd.com/read/37641280/post-ruminal-choline-supply-during-negative-nutrient-balance-alters-components-of-hepatic-mtor-signaling-and-plasma-amino-acids-in-lactating-holstein-cows
#19
JOURNAL ARTICLE
D N Sherlock, E Abdel-Hamied, R Bucktrout, Y Liang, M Miura, J J Loor
Choline requirements for dairy cattle are unknown. However, enhanced post-ruminal supply of choline may increase flux through the methionine cycle to spare Met for other functions such as protein synthesis and phosphatidylcholine (PC) synthesis during periods of negative nutrient balance (NNB). The objective was to investigate the effects of post-ruminal choline supply during a feed restriction-induced NNB on hepatic abundance and phosphorylation of mTOR (mechanistic target of rapamycin)-related signaling proteins, hepatic lipidome and plasma amino acids (AA)...
August 23, 2023: Journal of Dairy Science
https://read.qxmd.com/read/37602404/increased-levels-of-eif2a-inhibit-translation-by-sequestering-40s-ribosomal-subunits
#20
JOURNAL ARTICLE
Daisy J Grove, Daniel J Levine, Michael G Kearse
eIF2A was the first eukaryotic initiator tRNA carrier discovered but its exact function has remained enigmatic. Uncharacteristic of translation initiation factors, eIF2A is reported to be non-cytosolic in multiple human cancer cell lines. Attempts to study eIF2A mechanistically have been limited by the inability to achieve high yield of soluble recombinant protein. Here, we developed a purification paradigm that yields ∼360-fold and ∼6000-fold more recombinant human eIF2A from Escherichia coli and insect cells, respectively, than previous reports...
August 21, 2023: Nucleic Acids Research
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