PubMed

Related Articles Modern traditional Chinese medicine: Identifying, defining and usage of TCM components. Adv Pharmacol. 2020;87:113-158 Authors: Newman DJ Abstract TCM-based medications have been used for millennia in China and have always been "different" from current Western-based medicines in that they frequently are still mixtures of predominately plant products. From the early 20th Century, there has been a move to identify both the actual compounds in these mixes, and then over the past approximately 50years, to utilize early information for current diseases, with an example being artemisinin for treatment of malaria. Since that discovery, Western scientists, together with their Chinese counterparts, have begun to investigate how TCM compositions can be utilized to discover new agents, sometimes the actual TCM-based compound(s) but also by utilizing the pharmacophores from such preparations that have utility in human diseases. The examples in this review include artemisinin derivatives and their manifold bioactivities, indirubins and derivatives as antitumor agents, arsenicals predominately as treatment for leukemia, though extending into other cancer types. Finally, there are sections discussing the use of current computerized techniques that combine metabolomics, mass spectroscopy/HPLC, and network pharmacology with the aim of identifying the "active principles" in relevant TCM preparations and finally how high content screening can be utilized in conjunction with the other analytical techniques. PMID: 32089231 [PubMed - in process]

Related Articles Silver Nanoparticles Alter Soil Microbial Community Compositions and Metabolite Profiles in Unplanted and Cucumber-planted Soil. Environ Sci Technol. 2020 Feb 23;: Authors: Zhang H, Huang M, Zhang W, Gardea-Torresdey JL, White JC, Ji R, Zhao L Abstract The rapid development of nanotechnology makes environmental impact assessment a neccesity to ensure the sustainable use of engineered nanomaterials. Here, silver nanoparticles (AgNPs) at 100 mg/kg were added to soils in the absence or presence of cucumber (Cucumis sativa) plants for 60 days. The response of the soil microbial community and associated soil metabolites were investigated by 16S rRNA gene sequencing and gas chromatography-mass spectrometry (GC-MS) based metabolomics, respectively. The results show that AgNPs exposure significantly increased soil pH in both unplanted and cucumber-planted soils. The soil bacterial community structure was altered upon Ag exposure in both soils. Several functionally significant bacterial groups, which are associated with carbon-, nitrogen-, and phosphorus- cycling, were compromised by AgNPs in both unplanted and cucumber-planted soils. Generally, plants played a limited role on mediating the impacts of AgNPs on the bacterial community. Soil metabolomic analysis showed that AgNPs altered the metabolite profile in both unplanted and cucumber-planted soils. The significantly changed metabolites are involved in sugar and amino acid related metabolic pathways, indicating the perturbation of C and N metabolism, which is consistent with the bacterial community structure results. In addition, several fatty acids were significantly decreased upon exposure to AgNPs in both unplanted and cucumber-planted soils, suggesting the possible oxidative stress imposed on microbial cell membranes. These results provide valuable information for understanding the biological and biochemical impacts of AgNPs exposure on both plant species and on soil microbial communities; such understanding is needed to understand the risk posed by these materials in the environment. PMID: 32088952 [PubMed - as supplied by publisher]

Related Articles Rapid identification of absorbed components and metabolites of Gandou decoction in rat plasma and liver by UPLC-Q-TOF-MSE. J Chromatogr B Analyt Technol Biomed Life Sci. 2020 Jan 15;1137:121934 Authors: Xu L, Liu Y, Wu H, Zhou A Abstract Gandou Decoction (GDD), a well-known traditional Chinese medicine prescription, has been widely used for decades in clinical practice to treat Wilson's disease (WD) in China. However, due to lack of in vivo metabolism research, the absorbed components and metabolites of GDD have not been fully elucidated. In this study, a rapid and high-throughput ultra-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q-TOF-MSE) was applied to rapidly identify prototypes and metabolites after oral administration of GDD. On this basis, the possible metabolic pathways of the main prototypes were proposed between normal and copper-laden rats. As a result, a total of 89 GDD-related xenobiotics were detected in normal dosed rats, including 83 (36 prototypes and 47 metabolites) in plasma and 52 (21 prototypes and 31 metabolites) in liver; a total of 77 GDD-related xenobiotics were detected in copper-laden dosed rats, including 68 (31 prototypes and 37 metabolites) in plasma and 42 (19 prototypes and 23 metabolites) in liver. Our findings showed that anthraquinones, alkaloids and protostane triterpenoids as well as a few saponins, flavonoids, tannins and curcuminoids were the main absorbed chemical components of GDD in rat plasma; anthraquinones, protostane triterpenoids and curcuminoids were the major components in rat liver. Glucuronidation and sulfation were deduced to be the predominant metabolic pathways of GDD. Methylation, acetylation, reduction, hydroxylation, demethylation and deglycosylation were often occurred in the metabolic process. Furthermore, the holistic metabolic profile of GDD revealed that copper-laden rats and normal rats had certain differences in drug absorption and metabolism. This study offered a solid basis for ascertaining bioactive components and action mechanism of GDD. PMID: 31877432 [PubMed - indexed for MEDLINE]

Related Articles Functional cross-talk between allosteric effects of activating and inhibiting ligands underlies PKM2 regulation. Elife. 2019 07 02;8: Authors: Macpherson JA, Theisen A, Masino L, Fets L, Driscoll PC, Encheva V, Snijders AP, Martin SR, Kleinjung J, Barran PE, Fraternali F, Anastasiou D Abstract Several enzymes can simultaneously interact with multiple intracellular metabolites, however, how the allosteric effects of distinct ligands are integrated to coordinately control enzymatic activity remains poorly understood. We addressed this question using, as a model system, the glycolytic enzyme pyruvate kinase M2 (PKM2). We show that the PKM2 activator fructose 1,6-bisphosphate (FBP) alone promotes tetramerisation and increases PKM2 activity, but addition of the inhibitor L-phenylalanine (Phe) prevents maximal activation of FBP-bound PKM2 tetramers. We developed a method, AlloHubMat, that uses eigenvalue decomposition of mutual information derived from molecular dynamics trajectories to identify residues that mediate FBP-induced allostery. Experimental mutagenesis of these residues identified PKM2 variants in which activation by FBP remains intact but cannot be attenuated by Phe. Our findings reveal residues involved in FBP-induced allostery that enable the integration of allosteric input from Phe and provide a paradigm for the coordinate regulation of enzymatic activity by simultaneous allosteric inputs. PMID: 31264961 [PubMed - indexed for MEDLINE]

Related Articles Kynurenine Is a Cerebrospinal Fluid Biomarker for Bacterial and Viral Central Nervous System Infections. J Infect Dis. 2019 06 05;220(1):127-138 Authors: Sühs KW, Novoselova N, Kuhn M, Seegers L, Kaever V, Müller-Vahl K, Trebst C, Skripuletz T, Stangel M, Pessler F Abstract BACKGROUND: The tryptophan-kynurenine-nicotinamide adenine dinucleotide (oxidized; NAD+) pathway is closely associated with regulation of immune cells toward less inflammatory phenotypes and may exert neuroprotective effects. Investigating its regulation in central nervous system (CNS) infections would improve our understanding of pathophysiology and end-organ damage, and, furthermore, open doors to its evaluation as a source of diagnostic and/or prognostic biomarkers. METHODS: We measured concentrations of kynurenine (Kyn) and tryptophan (Trp) in 221 cerebrospinal fluid samples from patients with bacterial and viral (due to herpes simplex, varicella zoster, and enteroviruses) meningitis/encephalitis, neuroborreliosis, autoimmune neuroinflammation (due to anti-N-methyl-D-aspartate receptor [NMDA] encephalitis and multiple sclerosis), and noninflamed controls (ie, individuals with Bell palsy, normal pressure hydrocephalus, or Tourette syndrome). RESULTS: Kyn concentrations correlated strongly with CSF markers of neuroinflammation (ie, leukocyte count, lactate concentration, and blood-CSF-barrier dysfunction), were highly increased in bacterial and viral CNS infections, but were low or undetectable in NMDA encephalitis, multiple sclerosis, and controls. Trp concentrations were decreased mostly in viral CNS infections and neuroborreliosis. Multiple logistic regression analysis revealed that combinations of Kyn concentration, Trp concentration, and Kyn/Trp concentration ratio with leukocyte count or lactate concentration were accurate classifiers for the clinically important differentiation between neuroborreliosis, viral CNS infections, and autoimmune neuroinflammation. CONCLUSIONS: The Trp-Kyn-NAD+ pathway is activated in CNS infections and provides highly accurate CSF biomarkers, particularly when combined with standard CSF indices of neuroinflammation. PMID: 30721966 [PubMed - indexed for MEDLINE]

Related Articles Pre-diagnostic Serum Metabolomic Profiling of Prostate Cancer Survival. J Gerontol A Biol Sci Med Sci. 2019 05 16;74(6):853-859 Authors: Huang J, Weinstein SJ, Moore SC, Derkach A, Hua X, Mondul AM, Sampson JN, Albanes D Abstract Impaired metabolism may play a role in the development and lethality of prostate cancer, yet a comprehensive analysis of the interrelationships appears lacking. We measured 625 metabolites using ultrahigh performance liquid chromatography/mass spectrometry (LC-MS) and gas chromatography/mass spectrometry (GC-MS) of prediagnostic serum from 197 prostate cancer cases in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention (ATBC) Study (ages at diagnosis, 55-86 years). Cox proportional hazards models estimated associations between circulating metabolites and prostate cancer mortality for 1 SD differences (log-metabolite scale), adjusted for age, year of diagnosis, and disease stage. Associations between metabolite chemical classes and survival were examined through pathway analysis, and Cox models assessed the relationship with a sterol/steroid metabolite principal component analysis factor score. Elevated serum N-oleoyl taurine was significantly associated with prostate cancer-specific mortality (hazard ratios [HR] = 1.72 per 1 SD, p < .00008, Bonferroni-corrected threshold = 0.05/625; HR = 3.6 for highest vs lowest tertile, p < .001). Pathway analyses revealed a statistically significant association between lipids and prostate cancer death (p < .006, Bonferroni-corrected threshold = 0.05/8), and sterol/steroid metabolites showed the strongest chemical sub-class association (p = .0014, Bonferroni-corrected threshold = 0.05/45). In the principal component analysis, a 1-SD increment in the sterol/steroid metabolite score increased the risk of prostate cancer death by 46%. Prediagnostic serum N-oleoyl taurine and sterol/steroid metabolites were associated with prostate cancer survival. PMID: 29878065 [PubMed - indexed for MEDLINE]

Related Articles Dynamics in redox metabolism, from stoichiometry towards kinetics. Curr Opin Biotechnol. 2020 Feb 20;64:116-123 Authors: Verhagen KJ, van Gulik WM, Wahl SA Abstract Redox metabolism plays an essential role in the central metabolic network of all living cells, connecting, but at the same time separating, catabolic and anabolic pathways. Redox metabolism is inherently linked to the excretion of overflow metabolites. Overflow metabolism allows for higher substrate uptake rates, potentially outcompeting other microorganisms for the same substrate. Within dynamically changing environments, overflow metabolism can act as storage mechanism, as is shown in many recently described processes. However, for complete understanding of these mechanisms, the intracellular state of the metabolism must be elucidated. In recent years, progress has been made in the field of metabolomics to improve the accuracy and precision of measurements of intracellular and intercompartmental metabolites. This article highlights several of these recent advances, with focus on redox cofactor measurements, both fluorescence and mass spectrometry based. PMID: 32088622 [PubMed - as supplied by publisher]

Related Articles Exposure of ultrafine particulate matter causes glutathione redox imbalance in the hippocampus: A neurometabolic susceptibility to Alzheimer's pathology. Sci Total Environ. 2020 Feb 12;718:137267 Authors: Park SJ, Lee J, Lee S, Lim S, Noh J, Cho SY, Ha J, Kim H, Kim C, Park S, Lee DY, Kim E Abstract Particulate matter (PM) exposure is related to an increased risk of sporadic Alzheimer's disease (AD), the pathogenesis of which is explained by chronic neurometabolic disturbance. Therefore, PM-induced alterations in neurometabolism might herald AD. We aimed to identify brain region-specific changes in metabolic pathways associated with ultrafine particle (UFP) exposure and to determine whether such metabolic alterations are linked to susceptibility to AD. We constructed UFP exposure chambers and generated UFP by the pyrolysis method, which produces no toxic oxidized by-products of combustion, such as NOx and CO. Twenty male C57BL6 mice (11-12 months old) were exposed either to UFP or room air in the chambers for 3 weeks. One week following completion of UFP exposure, regional brain tissues, including the olfactory bulb, cortex, hippocampus, and cerebellum, were obtained and analyzed by metabolomics based on GC-MS and LC-MS, western blot analysis, and immunohistochemistry. Our results demonstrated that the metabolomic phenotype was distinct within the 4 different anatomical regions following UFP exposure. The highest level of metabolic change was identified in the hippocampus, a vulnerable region involved in AD pathogenesis. In this region, one of the key changes was perturbed redox homeostasis via alterations in the methionine-glutathione pathway. UFP exposure also induced oxidative stress and neuroinflammation, and importantly, increased Alzheimer's beta-amyloid levels in the hippocampus. These results suggest that inhaled UFP-induced perturbation in hippocampal redox homeostasis has a role in the pathogenesis of AD. Therefore, chronic exposure to UFP should be regarded as a cumulative environmental risk factor for sporadic AD. PMID: 32088476 [PubMed - as supplied by publisher]

Related Articles Metabolomic fingerprinting and genetic discrimination of four Hypericum taxa from Greece. Phytochemistry. 2020 Feb 19;:112290 Authors: Zeliou K, Koui EM, Papaioannou C, Koulakiotis NS, Iatrou G, Tsarbopoulos A, Papasotiropoulos V, Lamari FN Abstract Hypericum perforatum has plenty of uses in traditional medicine and is the source of top-selling herbal drugs and food supplements. The secondary metabolite chemistry for most of the nearly 500 Hypericum taxa is still unknown, even though they are used interchangeably. In the present study, we characterized four Hypericum populations from Achaia, Greece, belonging to H. perforatum ssp. veronense, H. perfoliatum, H. triquetrifolium, and an uninvestigated taxon, H. empetrifolium ssp. empetrifolium, in terms of their essential oils and polar bioactives in methanolic extracts via GC-MS, LC-HRMS, LC-DAD-MS, and HPLC-DAD. We also performed sequence analysis of nrITS to explore the genetic profile of these taxa and to examine whether their genotype is correlated to the metabolome. Sixty-three non-volatile compounds, phloroglucinols in their majority, and over one hundred (113) volatiles, mostly sesqui- and mono- terpenes, were detected. The concentration of the major polar constituents varied greatly among samples. In particular, phloroglucinols' diversity and abundance in H. empetrifolium ssp. empetrifolium was remarkable. The PCA and Biplot analysis revealed the contribution of each compound to the total chemodiversity and also revealed certain compounds that contribute to the discrimination of the samples. Sequence analysis of nrITS revealed different genetic profiles and markers which can be used for the identification of the four Hypericum taxa. The Mantel test showed a relatively strong correlation between the genetic profile and the volatile compounds and low with the main polar metabolites. PMID: 32087928 [PubMed - as supplied by publisher]

68 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/23PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

61 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/22PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

27 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/21PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

38 new pubmed citations were retrieved for your search. Click on the search hyperlink below to display the complete search results: metabolomics These pubmed results were generated on 2020/02/20PubMed comprises more than millions of citations for biomedical literature from MEDLINE, life science journals, and online books. Citations may include links to full-text content from PubMed Central and publisher web sites.

Glutamine metabolism in the proliferation of GS-expression pituitary tumor cells. Endocr Connect. 2020 Feb 01;: Authors: Hu J, Chen Q, Ding X, Zheng X, Tang X, Li S, Yang H Abstract OBJECTIVE: Many cancer cells cannot survive without exogenous glutamine (Gln)，however, cancer cells expressed glutamine synthetase (GS) do not have this restriction. Previous metabolomics studies have indicated that glutamine metabolism is altered during pituitary tumorigenesis. However, the main role of Gln in pituitary adenoma (PA) pathophysiology remains unknown. The aim of this study was to evaluate the expression of GS and the main role of Gln in human PAs. METHODS: We used cell proliferation assay and flow cytometry to assess the effect of Gln depletion on three different pituitary cell lines and human primary PA cells. Then investigated the expression level of Gln synthetase (GS) in 24 human PA samples. At last, we used LC-MS/MS to identify the differences in metabolites of PA cells after the blockage of both endogenous and exogenous Gln. RESULTS: PA cell lines showed different sensitivities to Gln starvation, and the sensitivity is correlated with GS expression level. GS expressed in 21 out of the 24 human PA samples. Furthermore, a positive p53 and ki-67 index was correlated with a higher GS expression level (p<0.05). Removal of both endogenous and exogenous Gln from GS-expressing PA cells resulted in blockage of nucleotide metabolism and cell cycle arrest. CONCLUSIONS: Our data indicate that GS is needed for PA cells to proliferation during Gln deprivation, and most human PA cells express GS and might have a negative response to exogenous Gln depletion. Moreover, Gln is mainly responsible for nucleotide metabolism in the proliferation of GS-expressing pituitary tumor cells. PMID: 32069221 [PubMed - as supplied by publisher]

The Aging Metabolome- Biomarkers to Hub Metabolites. Proteomics. 2020 Feb 18;:e1800407 Authors: Sharma R, Ramanathan A Abstract Aging biology is intimately associated with dysregulated metabolism, which is one of the hallmarks of aging. Aging related pathways such as mTOR and AMPK which are major targets of anti-aging interventions including rapamcyin, metformin and exercise, either directly regulate or intersect with metabolic pathways. In this review we outline numerous candidate bio-markers of aging that have emerged using metabolomics. Metabolomics studies also reveal that not all metabolites are created equally. A set of core 'hub' metabolites are emerging as central mediators of aging. The hub metabolites reviewed here are- Nicotinamide adenine dinucleotide (NAD+), reduced nicotinamide dinucleotide phosphate (NADPH), alpha ketoglutarate (aKG) and beta-hydroxybutyrate (βHB). These 'hub' metabolites have signaling and epigenetic roles along with their canonical roles as co-factors or intermediates of carbon metabolism. Together these hub metabolites suggest a central role of the TCA cycle in signaling and metabolic dysregulation associated with aging. This article is protected by copyright. All rights reserved. PMID: 32068959 [PubMed - as supplied by publisher]

Monitoring of the influence of long-term oxidative stress and ischemia on the condition of kidney using solid phase microextraction chemical biopsy coupled with liquid chromatography high resolution mass spectrometry. J Sep Sci. 2020 Feb 18;: Authors: Stryjak I, Warmuzińska N, Bogusiewicz J, Łuczykowski K, Bojko B Abstract The limiting factor in conventional quality assessments of transplanted organs, namely the invasiveness of tissue sample collection, has prompted much research on the field of transplantology to focus on the development of alternative evaluation methods of organ quality. In the present project, we undertake the challenge to address the need for a new analytical solution for graft quality assessments by using a novel metabolomic diagnostic protocol based on low-invasive solid-phase microextraction. Solid-phase microextraction probes of ca. 0.2 mm coated with 4 mm long mixed-mode extraction phase were inserted into rabbit kidneys immediately following euthanasia and after 2, 4, 6, and 21 h of preservation. LC-MS analysis of the extracts was performed with the use of a reversed phase column and a Q-Exactive Focus mass spectrometer operated in positive ionization mode. Statistical analysis of significantly changing compounds revealed metabolic profile changes in kidneys induced by ischemia and oxidative stress as a function of the duration of cold storage. The most pronounced alterations were reflected in levels of essential amino acids and purine nucleosides. Our findings demonstrate that the proposed approach may be successfully used to monitor changes in the metabolic profile of organs over time of preservation. This article is protected by copyright. All rights reserved. PMID: 32068348 [PubMed - as supplied by publisher]

Taurocholic acid inhibits features of age-related macular degeneration in vitro. Exp Eye Res. 2020 Feb 14;:107974 Authors: Warden C, Barnett J, Brantley MA Abstract Previous metabolomics studies from our lab found altered plasma levels of bile acids in patients with age-related macular degeneration (AMD) compared to controls. In this study, we investigated the ability of the bile acid taurocholic acid (TCA) to inhibit features of AMD modeled in vitro. Paraquat was used to induce oxidative stress in HRPEpiC primary retinal pigment epithelial (RPE) cells. Cells were treated with 300 μM paraquat alone or with TCA (10, 50, 100, 200, or 500 μM). RPE tight junction integrity was assessed via ZO-1 immunofluorescence and transepithelial electrical resistance (TEER) measurements. RF/6A macaque choroidal endothelial cells were treated with 100 ng/mL vascular endothelial growth factor (VEGF) to induce angiogenesis. The effect of TCA on VEGF-induced angiogenesis was evaluated with cell proliferation, cell migration, and tube formation assays. Addition of TCA at 100 (P = 8.6 × 10-4), 200 (P = 0.0035), and 500 (P = 2.1 × 10-4) μM resulted in significant preservation of TEER in paraquat treated cells. In RF/6A cells, TCA did not significantly affect VEGF-induced cell proliferation. VEGF-induced migration of RF/6A cells was significantly inhibited at TCA concentrations of 100 (P = 0.010), 200 (P = 0.023) and 500 (P = 0.0049) μM. VEGF-induced tube formation was significantly inhibited when treated with 200 (P = 0.014) and 500 (P = 7.1 × 10-4) μM TCA. In vitro, TCA promoted RPE cell and diminished VEGF-induced choroidal endothelial cell migration and tube formation. This suggests that TCA may have protective effects against both degenerative and neovascular AMD. PMID: 32067977 [PubMed - as supplied by publisher]

Precision Medicine Approach in Prostate Cancer. Curr Pharm Des. 2020 Feb 17;: Authors: Assadi M, Jokar N, Ghasemi M, Nabipour I, Gholamrezanezhad A, Ahmadzadehfar H Abstract Prostate cancer is the most prevalent form of cancer and the second cause of death in men worldwide. Various diagnostic and treatment procedures are available for this type of malignancy, but High-risk or locally advanced prostate cancers showed the potential to develop to lethal phase that can be causing dead. Therefore, new approaches are needed to prolong patient survival and provide a better quality of life. Precision medicine is a novel emerging field that has an essential role in identifying new sub-classifications of disease and guiding treatment based on individual multi-omics data. Multi-omics approaches include the use of genomics, transcriptomics, proteomics, metabolomics, epigenomics and phenomics data to unravel the complexity of a disease-associated biological network, to predict prognostic biomarkers, and to identify new targeted drugs for individual cancer patients. We review the impact of multi-omics data in the framework of systems biology in the era of precision medicine, emphasising the combination of molecular imaging modalities with high-throughput techniques and the new treatments that target metabolic pathways involved in prostate cancer. PMID: 32067601 [PubMed - as supplied by publisher]

Related Articles Transcriptional coactivator with PDZ-binding motif suppresses the expression of steroidogenic enzymes by nuclear receptor 4 A1 in Leydig cells. FASEB J. 2020 Feb 17;: Authors: Shin JH, Lee G, Jeong MG, Kim HK, Won HY, Choi Y, Lee JH, Nam M, Choi CS, Hwang GS, Hwang ES Abstract Transcriptional coactivator with PDZ-binding motif (TAZ) plays crucial role in maintaining testicular structure and function via regulation of senescence of spermatogenic cells. However, it remains unclear whether TAZ is involved in testosterone biosynthesis in testicular Leydig cells. We found that TAZ deficiency caused aberrant Leydig cell expansion and increased lipid droplet formation, which was significantly associated with increased lipogenic enzyme expression. Additionally, the expression of key steroidogenic enzymes, including steroidogenic acute regulatory protein, cytochrome P450 (CYP) 11A1, CYP17A1, and 3β-hydroxysteroid dehydrogenase, was greatly increased in TAZ-deficient testes and primary Leydig cells. Interestingly, the transcriptional activity of nuclear receptor 4 A1 (NR4A1) was dramatically suppressed by TAZ; however, the protein expression and the subcellular localization of NR4A1 were not affected by TAZ. TAZ directly associated with the N-terminal region of NR4A1 and substantially suppressed its DNA-binding and transcriptional activities. Stable expression of TAZ in the mouse Leydig TM3 cell line decreased the expression of key steroidogenic enzymes, whereas knockdown of endogenous TAZ in TM3 cells increased transcripts of steroidogenic genes induced by NR4A1. Consistently, testosterone production was enhanced within TAZ-deficient Leydig cells. However, TAZ deficiency resulted in decreased testosterone secretion caused by dysfunctional mitochondria and lysosomes. Therefore, TAZ plays essential role in NR4A1-induced steroidogenic enzyme expression and testosterone production in Leydig cells. PMID: 32067268 [PubMed - as supplied by publisher]

Related Articles Germinal center B cells selectively oxidize fatty acids for energy while conducting minimal glycolysis. Nat Immunol. 2020 Feb 17;: Authors: Weisel FJ, Mullett SJ, Elsner RA, Menk AV, Trivedi N, Luo W, Wikenheiser D, Hawse WF, Chikina M, Smita S, Conter LJ, Joachim SM, Wendell SG, Jurczak MJ, Winkler TH, Delgoffe GM, Shlomchik MJ Abstract Germinal center B cells (GCBCs) are critical for generating long-lived humoral immunity. How GCBCs meet the energetic challenge of rapid proliferation is poorly understood. Dividing lymphocytes typically rely on aerobic glycolysis over oxidative phosphorylation for energy. Here we report that GCBCs are exceptional among proliferating B and T cells, as they actively oxidize fatty acids (FAs) and conduct minimal glycolysis. In vitro, GCBCs had a very low glycolytic extracellular acidification rate but consumed oxygen in response to FAs. [13C6]-glucose feeding revealed that GCBCs generate significantly less phosphorylated glucose and little lactate. Further, GCBCs did not metabolize glucose into tricarboxylic acid (TCA) cycle intermediates. Conversely, [13C16]-palmitic acid labeling demonstrated that GCBCs generate most of their acetyl-CoA and acetylcarnitine from FAs. FA oxidation was functionally important, as drug-mediated and genetic dampening of FA oxidation resulted in a selective reduction of GCBCs. Hence, GCBCs appear to uncouple rapid proliferation from aerobic glycolysis. PMID: 32066950 [PubMed - as supplied by publisher]