N-Farnesyl-norcantharimide Inhibits Progression of Human Leukemic Jurkat T Cells Through Up-regulation of Tumor Suppressor Gene and Down-regulation of Steroid Biosynthesis, Metabolic Pathways, and Fatty Acid Metabolism

2016 ◽  
Author(s):  
Cheng-Deng Kuo ◽  
En-Tung Tsai ◽  
Ming-Che Chang ◽  
Jin-Yi Wu ◽  
Hui-Fen Liao ◽  
...  
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Suppressor Gene ◽  
Steroid Biosynthesis ◽  
Jurkat T Cells

scholarly journals Modulation of ATP8B1 Gene expression in Colorectal Cancer Cells Suggest its Role as a Tumor Suppressor

2020 ◽  
Author(s):  
Saleh Althenayyan ◽  
Amal AlGhamdi ◽  
Mohammed H AlMuhanna ◽  
Esraa Hawsa ◽  
Dalal Aldeghaither ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Fatty Acid ◽  
Tumor Suppressor ◽  
Cell Line ◽  
Cancer Progression ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Suppressor Gene ◽  
Sporadic Colorectal Cancer ◽  
Limited Information

Sporadic colorectal cancer (CRC) develops through distinct molecular events. Loss of 18q chromosome is a conspicuous event in the progression of adenoma to carcinoma. There is limited information regarding the molecular effectors of this event. Earlier, we had reported ATP8B1 as a novel gene associated with CRC. ATP8B1 belongs to the family of P-type ATPases (P4 ATPase) that primarily function to facilitate the translocation of phospholipids. In this study, we attempt to implicate ATP8B1 gene located on chromosome 18q as a tumor suppressor gene. We studied indigenous patient data and confirmed the reduced expression of ATP8B1 in tumor samples. CRC cell lines were engineered with reduced and enhanced levels of ATP8B1 which provided a tool to study its role on cancer progression. Forced reduction of ATP8B1 expression either by CRISPR/Cas9 or shRNA was associated with increased growth and proliferation of CRC cell line - HT29. In contrast, overexpression of ATP8B1 resulted in reduced growth and proliferation of SW480 cell line. We generated a network of genes that are downstream of ATP8B1. Further, we provide predicted effect of modulation of ATP8B1 levels on this network and possible effect on fatty acid metabolism related genes. These results provide evidence in support of ATP8B1 being a tumor suppressor that may affect fatty acid metabolism in CRC.

scholarly journals Redox, amino acid, and fatty acid metabolism intersect with bacterial virulence in the gut

2018 ◽  
Vol 115 (45) ◽  
pp. E10712-E10719 ◽  
Author(s):  
Reed Pifer ◽  
Regan M. Russell ◽  
Aman Kumar ◽  
Meredith M. Curtis ◽  
Vanessa Sperandio
Keyword(s):  
Fatty Acid ◽  
High Throughput ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Virulence Genes ◽  
Acid Metabolism ◽  
Feedback Mechanism ◽  
Regulatory Pathways ◽  
Successful Infection ◽  
Cellular Circuits

The gut metabolic landscape is complex and is influenced by the microbiota, host physiology, and enteric pathogens. Pathogens have to exquisitely monitor the biogeography of the gastrointestinal tract to find a suitable niche for colonization. To dissect the important metabolic pathways that influence virulence of enterohemorrhagicEscherichia coli(EHEC), we conducted a high-throughput screen. We generated a dataset of regulatory pathways that control EHEC virulence expression under anaerobic conditions. This unraveled that the cysteine-responsive regulator, CutR, converges with the YhaO serine import pump and the fatty acid metabolism regulator FadR to optimally control virulence expression in EHEC. CutR activates expression of YhaO to increase activity of the YhaJ transcription factor that has been previously shown to directly activate the EHEC virulence genes. CutR enhances FadL, which is a pump for fatty acids that represses inhibition of virulence expression by FadR, unmasking a feedback mechanism responsive to metabolite fluctuations. Moreover, CutR and FadR also augment murine infection byCitrobacter rodentium, which is a murine pathogen extensively employed as a surrogate animal model for EHEC. This high-throughput approach proved to be a powerful tool to map the web of cellular circuits that allows an enteric pathogen to monitor the gut environment and adjust the levels of expression of its virulence repertoire toward successful infection of the host.

scholarly journals Allogeneic T Cells up-Regulate Fatty Acid Metabolism and Can Be Targeted Through Metabolic Inhibition of Fatty Acid Oxidation

2013 ◽  
Vol 19 (2) ◽  
pp. S318-S319
Author(s):  
Craig A. Byersdorfer ◽  
Victor Tkachev ◽  
Stefanie Goodell ◽  
Stacy Sandquist ◽  
Anthony W. Opipari ◽  
...  
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Inhibition ◽  
Acid Oxidation

scholarly journals Cord Blood CD8+ T Cells Have a Natural Propensity to Express IL-4 in a Fatty Acid Metabolism and Caspase Activation-Dependent Manner

2018 ◽  
Vol 9 ◽  
Author(s):  
Yuxia Zhang ◽  
Jovana Maksimovic ◽  
Bing Huang ◽  
David Peter De Souza ◽  
Gaetano Naselli ◽  
...  
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Cord Blood ◽  
Fatty Acid Metabolism ◽  
Cd8 T Cells ◽  
Acid Metabolism ◽  
Dependent Manner ◽  
Caspase Activation

scholarly journals Signatures of mito-nuclear climate adaptation in a warbler species complex

2020 ◽  
Author(s):  
Silu Wang ◽  
Madelyn J. Ore ◽  
Else K. Mikkelsen ◽  
Julie Lee-Yaw ◽  
Sievert Rohwer ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Species Complex ◽  
Acid Metabolism ◽  
Climate Adaptation ◽  
Climatic Conditions ◽  
Secondary Contact ◽  
Mitochondrial Fatty Acid ◽  
Genetic Patterns

AbstractMitochondrial (mtDNA) and nuclear (nDNA) genes interact to govern metabolic pathways of mitochondria. When differentiated populations interbreed at secondary contact, incompatibilities between mtDNA of one population and nDNA of the other could result in low fitness of hybrids. Hermit Warblers (S. occidentalis abbreviated as HEWA) and inland Townsend’s Warblers (Setophaga townsendi, abbreviated as i-TOWA) exhibit distinct mtDNA haplotypes and a few nDNA regions of high differentiation, whereas coastal TOWA (c-TOWA) displays a mix of these genetic patterns consistent with ancient hybridization of HEWA and i-TOWA. Of the few highly-differentiated nDNA regions between i-TOWA and HEWA, two of these regions (on chromosome 5 and Z, respectively) are also differentiated between c-TOWA and i-TOWA, similar to the mtDNA pattern. These two nDNA regions are associated with mitochondrial fatty acid metabolism. Moreover, these nDNA regions are correlated with mtDNA ancestries among sites, a pattern consistent with mito-nuclear co-adaptation. Such mito-nuclear coevolution might be driven by climate-related selection, because the mito-nuclear ancestry is correlated with climatic conditions among sampling sites. These results suggest that cryptic differentiation in this species complex has been shaped by climate-correlated adaptation associated with mito-nuclear fatty acid metabolism.

scholarly journals Pathomechanisms in schwannoma development and progression

Oncogene ◽  
2020 ◽  
Vol 39 (32) ◽  
pp. 5421-5429 ◽  
Author(s):  
Dario-Lucas Helbing ◽  
Alexander Schulz ◽  
Helen Morrison
Keyword(s):  
Extracellular Matrix ◽  
T Cells ◽  
Nervous System ◽  
Tumor Microenvironment ◽  
Tumor Suppressor ◽  
Tumor Suppressor Gene ◽  
Schwann Cells ◽  
Cell Types ◽  
Suppressor Gene ◽  
Different Cell Types

Abstract Schwannomas are tumors of the peripheral nervous system, consisting of different cell types. These include tumorigenic Schwann cells, axons, macrophages, T cells, fibroblasts, blood vessels, and an extracellular matrix. All cell types involved constitute an intricate “tumor microenvironment” and play relevant roles in the development and progression of schwannomas. Although Nf2 tumor suppressor gene-deficient Schwann cells are the primary tumorigenic element and principle focus of current research efforts, evidence is accumulating regarding the contributory roles of other cell types in schwannoma pathology. In this review, we aim to provide an overview of intra- and intercellular mechanisms contributing to schwannoma formation. “Genes load the gun, environment pulls the trigger.” -George A. Bray

scholarly journals Comparative analysis of powdery mildew resistant and susceptible cultivated cucumber (Cucumis sativus L.) varieties to reveal the metabolic responses to Sphaerotheca fuliginea infection

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Peng Zhang ◽  
Yuqiang Zhu ◽  
Shengjun Zhou
Keyword(s):  
Fatty Acid ◽  
Powdery Mildew ◽  
Cucumis Sativus ◽  
Fatty Acid Metabolism ◽  
Metabolic Pathways ◽  
Acid Metabolism ◽  
Susceptible Variety ◽  
Metabolic Responses ◽  
Resistant Variety ◽  
Sphaerotheca Fuliginea

Abstract Background Cucumber (Cucumis sativus L.) is a widely planted vegetable crop that suffers from various pathogen infections. Powdery mildew (PM) is typical disease caused by Sphaerotheca fuliginea infection and destroys the production of cucumber. However, the metabolic responses to S. fuliginea infection are largely unknown. Results In our study, a PM resistant variety ‘BK2’ and a susceptible variety ‘H136’ were used to screen differentially accumulated metabolites (DAMs) and differentially expressed genes (DEGs) under S. fuliginea infection. Most of DEGs and DAMs were enriched in several primary and secondary metabolic pathways, including flavonoid, hormone, fatty acid and diterpenoid metabolisms. Our data showed that many flavonoid-related metabolites were significantly accumulated in BK2 rather than H136, suggesting an essential role of flavonoids in formation of resistant quality. Changes in expression of CYP73A, CYP81E1, CHS, F3H, HCT and F3’M genes provided a probable explanation for the differential accumulation of flavonoid-related metabolites. Interestingly, more hormone-related DEGs were detected in BK2 compared to H136, suggesting a violent response of hormone signaling pathways in the PM-resistant variety. The number of fatty acid metabolism-related DAMs in H136 was larger than that in BK2, indicating an active fatty acid metabolism in the PM-susceptible variety. Conclusions Many differentially expressed transcription factor genes were identified under S. fuliginea infection, providing some potential regulators for the improvement of PM resistance. PM resistance of cucumber was controlled by a complex network consisting of various hormonal and metabolic pathways.

scholarly journals Nanoparticle-Mediated Lipid Metabolic Reprogramming of T Cells in Tumor Microenvironments for Immunometabolic Therapy

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Dongyoon Kim ◽  
Yina Wu ◽  
Qiaoyun Li ◽  
Yu-Kyoung Oh
Keyword(s):  
T Cells ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Tumor Microenvironment ◽  
Fatty Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Reprogramming ◽  
Killing Effect ◽  
Tumor Tissues

Highlights aCD3/F/AN, anti-CD3e f(ab′)2 fragment-modified and fenofibrate-encapsulated amphiphilic nanoparticle, reprogrammed mitochondrial lipid metabolism of T cells. aCD3/F/AN specifically activated T cells in glucose-deficient conditions mimicking tumor microenvironment, and exerted an effector killing effect against tumor cells. In vivo treatment with aCD3/F/AN increased T cell infiltration, cytokine production, and prevented tumor growth. Abstract We report the activation of anticancer effector functions of T cells through nanoparticle-induced lipid metabolic reprogramming. Fenofibrate was encapsulated in amphiphilic polygamma glutamic acid-based nanoparticles (F/ANs), and the surfaces of F/ANs were modified with an anti-CD3e f(ab′)2 fragment, yielding aCD3/F/ANs. An in vitro study reveals enhanced delivery of aCD3/F/ANs to T cells compared with plain F/ANs. aCD3/F/AN-treated T cells exhibited clear mitochondrial cristae, a higher membrane potential, and a greater mitochondrial oxygen consumption rate under glucose-deficient conditions compared with T cells treated with other nanoparticle preparations. Peroxisome proliferator-activated receptor-α and downstream fatty acid metabolism-related genes are expressed to a greater extent in aCD3/F/AN-treated T cells. Activation of fatty acid metabolism by aCD3/F/ANs supports the proliferation of T cells in a glucose-deficient environment mimicking the tumor microenvironment. Real-time video recordings show that aCD3/F/AN-treated T cells exerted an effector killing effect against B16F10 melanoma cells. In vivo administration of aCD3/F/ANs can increase infiltration of T cells into tumor tissues. The treatment of tumor-bearing mice with aCD3/F/ANs enhances production of various cytokines in tumor tissues and prevented tumor growth. Our findings suggest the potential of nanotechnology-enabled reprogramming of lipid metabolism in T cells as a new modality of immunometabolic therapy.

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