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PDRG1 at the interface between intermediary metabolism and oncogenesis

World Journal of Biological Chemistry 2017年第4期8卷 175-186页

作者： Maríaángeles Pajares Department of Chemical and Physical Biology Centro de Investigaciones Biológicas(CSIC)Madrid 28040Spain Instituto de Investigación Sanitaria La Paz(IdiPAZ) Madrid 28046Spain

PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.

关键词： Epigenetic modifications Glutathione Methylation Oncogenes intermediary metabolism p53 and DNA damage-regulated gene 1 Protein complexes R2TP/prefoldin complex S-adenosylmethionine synthesis Redox stress

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Exploring the effects of dietary inulin in rainbow trout fed a high‑starch,100%plant‑based diet

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Journal of Animal Science and Biotechnology 2024年第2期15卷 713-732页

作者： Raphaël Defaix Jep Lokesh Laura Frohn Mickael Le Bechec Thierry Pigot Vincent Veron Anne Surget Sandra Biasutti Frederic Terrier Sandrine Skiba-Cassy Jerome Roy Stephane Panserat Karine Ricaud Universite de Pau Et Des Pays de L’Adour E2S UPPAINRAENUMEASaint‑Pee‑Sur‑NivelleFrance Universite de Pau Et Des Pays de L’Adour E2S UPPACNRSIMT Mines AlesIPREMPauFrance Universite de Pau Et Des Pays de L’Adour E2S UPPAIUT des Pays de l’AdourDepartement Genie BiologiqueMont de MarsanFrance.

Background High dietary carbohydrates can spare protein in rainbow trout(Oncorhynchus mykiss)but may affect growth and ***,a prebiotic,could have nutritional and metabolic effects,along with anti-inflammatory properties in teleosts,improving growth and *** tested this hypothesis in rainbow trout by feeding them a 100%plant-based diet,which is a viable alternative to fishmeal and fish oil in aquaculture *** a two-factor design,we examined the impact of inulin(2%)as well as the variation in the carbohydrates(CHO)/plant protein ratio on rainbow *** assessed the influence of these factors on zootechnical parameters,plasma metabolites,gut microbiota,production of short-chain fatty acids and lactic acid,as well as the expression of free-fatty acid receptor genes in the mid-intestine,intermediary liver metabolism,and immune markers in a 12-week feeding *** The use of 2%inulin did not significantly change the fish intestinal microbiota,but interestingly,the high CHO/protein ratio group showed a change in intestinal microbiota and in particular the beta diversity,with 21 bacterial genera affected,including Ralstonia,Bacillus,and 11 lactic-acid producing *** were higher levels of butyric,and valeric acid in groups fed with high CHO/protein diet but not with *** high CHO/protein group showed a decrease in the expression of pro-inflammatory cytokines(il1b,il8,and tnfa)in liver and a lower expression of the genes coding for tight-junction proteins in mid-intestine(tjp1a and tjp3).However,the 2%inulin did not modify the expression of plasma immune ***,inulin induced a negative effect on rainbow trout growth performance irrespective of the dietary *** With a 100%plant-based diet,inclusion of high levels of carbohydrates could be a promising way for fish nutrition in aquaculture through a protein sparing effect whereas the supplementation of 2%inulin does not appear to improve the use of CHO wh

关键词： Aquaculture Fish nutrition Gut microbiota Immune markers intermediary metabolism Inulin Prebiotic Rainbow trout Short-chain fatty acids

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Supplying the trip to antibody production-nutrients,signaling,and the programming of cellular metabolism in the mature B lineage

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Cellular & Molecular Immunology 2022年第3期19卷 352-369页

作者： Mark R.Boothby Shawna K.Brookens Ariel L.Raybuck Sung Hoon Cho Department of Pathology Microbiology&ImmunologyMolecular Pathogenesis DivisionVanderbilt University Medical CenterNashvilleTN37232USA Department of Medicine Rheumatology&Immunology DivisionVanderbilt University Medical CenterNashvilleTN37232USA Cancer Biology Program Vanderbilt UniversityNashvilleTN37232USA Vanderbilt Institute of Infection Inflammationand ImmunologyNashvilleTN37232USA

The COVID pandemic has refreshed and expanded recognition of the vital role that sustained antibody(Ab)secretion plays in our immune defenses against microbes and of the importance of vaccines that elicit Ab protection against *** this backdrop,it is especially timely to review aspects of the molecular programming that govern how the cells that secrete Abs arise,persist,and meet the challenge of secreting vast amounts of these *** plasmablasts and plasma cells(PCs)are the primary sources of secreted Abs,the process leading to the existence of these cell types starts with naive B lymphocytes that proliferate and differentiate toward several potential *** each step,cells reside in specific microenvironments in which they not only receive signals from cytokines and other cell surface receptors but also draw on the interstitium for *** in turn influence flux through intermediary metabolism and sensor enzymes that regulate gene transcription,translation,and *** review will focus on nutrient supply and how sensor mechanisms influence distinct cellular stages that lead to PCs and their adaptations as factories dedicated to Ab *** findings of this group and others,sometimes exhibiting differences,will be summarized with regard to the journey to a distinctive metabolic program in PCs.

关键词： B lymphocyte Plasma cell intermediary metabolism Glucose Glutamine Fatty acid Signal transduction

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Pipeline of New Drug Treatment for Non-alcoholic Fatty Liver Disease/Metabolic Dysfunction-associated Steatotic Liver Disease

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Journal of Clinical and Translational Hepatology 2024年第9期12卷 802-814页

作者： Ye Hu Chao Sun Ying Chen Yu-Dong Liu Jian-Gao Fan Department of Gastroenterology Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Geriatrics Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina Department of Gastroenterology Changxing branch of Xin Hua Hospital Affiliated to Shanghai Jiao Tong University School of MedicineShanghaiChina

Given the global prevalence and rising incidence of metabolic dysfunction-associated steatotic liver disease(MASLD),the absence of licensed medications is striking.A deeper understanding of the heterogeneous nature of MASLD has recently contributed to the discovery of novel groups of agents and the potential repurposing of currently available *** therapies center on four major *** the close relationship between MASLD and type 2 diabetes,the first approach involves antidiabetic medications,including incretins,thiazolidinedione insulin sensitizers,and sodium-glucose cotransporter 2 *** second approach targets hepatic lipid accumulation and the resultant metabolic *** in this group include peroxisome proliferatoractivated receptor agonists(e.g.,pioglitazone,elafibranor,saroglitazar),bile acid-farnesoid X receptor axis regulators(obeticholic acid),de novo lipogenesis inhibitors(aramchol,NDI-010976),and fibroblast growth factor 21/19 *** third approach focuses on targeting oxidative stress,inflammation,and *** in this group include antioxi-dants(vitamin E),tumor necrosis factor a pathway regulators(emricasan,pentoxifylline,ZSP1601),and immune modulators(cenicriviroc,belapectin).The final group targets the gut(IMM-124e,solithromycin).Combination therapies targeting different pathogenetic pathways may provide an alternative to MASLD treatment with higher efficacy and fewer side *** review aimed to provide an update on these medications.

关键词： NAFLD MASLD Clinical trial Medication Hypoglycemic agents intermediary metabolism

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