• However, in contrast to lipopolysaccharide, CD40 signal is able to drive pro-inflammatory and anti-tumorigenic polarization by some yet undefined metabolic programming. (acir.org)
  • ABSTRACT: Exposure of lipopolysaccharide triggers macrophage pro-inflammatory polarization accompanied by metabolic reprogramming, characterized by elevated aerobic glycolysis and a broken tricarboxylic acid cycle. (acir.org)
  • Dr. Otto Warburg first described, more than 80 years ago, that a fundamental biochemical difference between tumor cells and their normal counterparts was that tumor cells rely on aerobic glycolysis for ATP generation, unlike most normal differentiated cells of the body, which use mitochondrial oxidative phosphorylation. (aacrjournals.org)
  • Mitochondria provide most of the cellular energy via their oxidative phosphorylation (OXPHOS) system, which requires the coordinated expression of genes encoded by both the nuclear (nDNA) and mitochondrial genomes (mtDNA). (biomed.news)
  • He found that, even in the presence of ample oxygen, cancer cells prefer to metabolize glucose by glycolysis, a seeming paradox as glycolysis, when compared to oxidative phosphorylation, is a less efficient pathway for producing ATP (Warburg, 1956). (pharmaceuticalintelligence.com)
  • The mammalian genome comprises nuclear DNA (nDNA) derived from both parents and mitochondrial DNA (mtDNA) that is maternally inherited and encodes essential proteins required for oxidative phosphorylation. (regenerativemedicine.net)
  • In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. (wikipedia.org)
  • As such, succinate links cellular metabolism, especially ATP formation, to the regulation of cellular function. (wikipedia.org)
  • Dysregulation of succinate synthesis, and therefore ATP synthesis, happens in some genetic mitochondrial diseases, such as Leigh syndrome, and Melas syndrome, and degradation can lead to pathological conditions, such as malignant transformation, inflammation and tissue injury. (wikipedia.org)
  • reported that CD40-mediated signaling boosted fatty acid oxidation (FAO) and glutamine metabolism to promote epigenetic reprogramming of macrophages towards pro-inflammatory/anti-tumorigenic polarization. (acir.org)
  • Here we show that CD40 activation triggers fatty acid oxidation (FAO) and glutamine metabolism to promote ATP citrate lyase-dependent epigenetic reprogramming of pro-inflammatory genes and anti-tumorigenic phenotypes in macrophages. (acir.org)
  • Together these data show that metabolic reprogramming, which includes FAO and glutamine metabolism, controls the activation of pro-inflammatory and anti-tumorigenic polarization, and highlight a therapeutic potential of metabolic preconditioning of tumor-associated macrophages before agonistic anti-CD40 treatments. (acir.org)
  • Melanin, especially eumelanin, has antioxidant properties, and MGST1 KD melanoma cells are under higher oxidative stress, with increased reactive oxygen species, decreased antioxidant capacities, reduced energy metabolism and ATP production, and lower proliferation rates in 3D culture. (bvsalud.org)
  • The specialized function of the normal prostate glandular epithelium to produce and secrete enormously high levels of citrate involves and requires unique intermediary metabolism activities that are not generally associated with other normal mammalian cells. (biomedcentral.com)
  • These genetic/metabolic relationships have important consequences on citrate-related metabolism, bioenergetics, cell proliferation and invasive capabilities of the malignant cells, which result in tumor-suppression characteristics. (biomedcentral.com)
  • Here, we find that dysregulation of propionate metabolism produces a pro-aggressive signature in breast and lung cancer cells, increasing their metastatic potential. (biomed.news)
  • For example, an upregulated metabolism may result in the build up of toxic metabolites, including lactate and noncanonical nucleotides, which must be disposed of (F). Moreover, cancer cells may also exhibit a high energetic demand, for which they must either increase flux through normal ATP-generating processes, or else rely on an increased diversity of fuel sources (G). (pharmaceuticalintelligence.com)
  • Genetic ablation of Ldha (encoding lactate dehydrogenase) and Gls (encoding glutaminase 1) impaired anti-CD40 monoclonal antibody-induced antitumor responses and re-education of tumor-associated macrophages. (acir.org)
  • The genetic/metabolic relationships in normal prostate glandular epithelium are driven by the unique function to accumulate and secrete citrate. (biomedcentral.com)
  • Imatinib (STI571) works by binding close to the ATP binding site, locking it in a closed or self-inhibited conformation, therefore inhibiting the enzyme activity of the protein semicompetitively. (medchemexpress.com)
  • They are inactive forms of the enzyme argininosuccinate lyase. (lookformedical.com)
  • Like the prokaryotic system, mitochondria have no membrane-based compartmentalization to separate the different steps of mtDNA maintenance and expression and depend entirely on nDNA-encoded factors imported into the organelle. (biomed.news)
  • In malignancy, the normal zinc-accumulating citrate-producing epithelial cells are metabolically transformed to citrate-oxidizing cells that lose the ability to accumulate zinc. (biomedcentral.com)
  • the tri6 gene, encoding a zinc finger protein involved in the regulation of trichothecene biosynthesis, from Fusarium sporotrichioides (Proctor et al. (justia.com)
  • Other genes in the trichothecene biosynthetic pathway have been cloned including the tri3 gene, encoding a 15-O-acetyltransferase, from Fusarium sporotrichioides (McCormick et al. (justia.com)
  • the tri4 gene, encoding a cytochrome P450 monooxygenase, from Fusarium sporotrichioides (Hohn et al. (justia.com)
  • c-Kit (Mast/stem cell growth factor receptor, SCFR or CD117) is a proteinthat in humans is encoded by the KIT gene. (medchemexpress.com)
  • ATP-citrate lyase Mouse Monoclonal Antibody detects endogenous levels of ATP-citrate lyase protein. (ebiocell.com)
  • The following product was used in this experiment: ATP Citrate Lyase Polyclonal Antibody from Thermo Fisher Scientific, catalog # PA5-78712, RRID AB_2745828. (thermofisher.com)
  • Samples were loaded onto a 5% SDS-PAGE gel and probed with an ATP citrate lyase polyclonal antibody (Product # PA5-29495) at a dilution of 1:1000. (siderac.com)
  • ATP citrate lyase (ACLY) is an enzyme that in animals represents an important step in fatty acid biosynthesis. (siderac.com)
  • ATP citrate lyase/ACLY cDNA clones are full length sequence confirmed and expression validated. (siderac.com)
  • The gene encoding ATP-citrate lyase, designated ACLY, was mapped to human chromosome 17q12-q21 by PCR on a panel of human/rodent somatic cell hybrids and localized to 17q21.1 by PCR on a panel of radiation hybrids. (siderac.com)
  • ATP citrate lyase (ACLY), an important enzyme involved in lipid biogenesis linked with glucose metabolism, catalyzes the conversion of citrate to oxaloacetic acid (OAA) and acetyl-CoA. (siderac.com)
  • In addition, PD-1 inactivation enforces ATP citrate lyase (ACLY) activity, which generates extramitochondrial acetyl-CoA for histone acetylation to enable hyperactivity of activating protein 1 (AP-1) transcription factors. (bvsalud.org)
  • It catalyzes the formation of acetyl-CoA and oxaloacetate from citrate and CoA with a concomitant hydrolysis of ATP to ADP and phosphate. (thermofisher.com)
  • J. Bgee i: ENSMUSG00000020917, Expressed in inguinal mammary gland and 345 other tissues: The 4 substrates of this enzyme are ADP, phosphate, acetyl-CoA, and oxaloacetate, whereas its 3 products are ATP, citrate, and CoA. (siderac.com)
  • citrate and CoA into acetyl-CoA and oxaloacetate, along with the hydrolysis of ATP. (siderac.com)
  • The Citrate Lyase (ACL) is the main cytosolic enzyme that converts the citrate exported from mitochondria by the SLC25A1 carrier in Acetyl Coenzyme A (acetyl-CoA) and oxaloacetate. (siderac.com)
  • An enzyme that, in the presence of ATP and COENZYME A, catalyzes the cleavage of citrate to yield acetyl CoA, oxaloacetate, ADP, and ORTHOPHOSPHATE. (lookformedical.com)
  • In enzymology, an ATP citrate synthase (EC 2.3.3.8) is an enzyme that catalyzes the chemical reaction. (siderac.com)
  • In nervous tissue, ATP citrate-lyase may be involved in the biosynthesis of acetylcholine. (thermofisher.com)
  • In some embodiments, the at least one heterologous nucleic acid encodes one or more polypeptides involved in the biosynthesis of an iron co-factor such as heme (e.g. (justia.com)
  • ADP + phosphate + acetyl-CoA + oxaloacetate ⇌ ATP + citrate + CoA. (siderac.com)
  • A definitive role for ATP citrate lyase in tumorigenesis has emerged from ATP citrate lyase RNAi and chemical inhibitor studies, showing that ATP citrate lyase inhibition limits tumor cell proliferation and survival and induces differentiation in vitro. (siderac.com)
  • The PDCD1-encoded immune checkpoint receptor PD-1 is a key tumor suppressor in T cells that is recurrently inactivated in T cell non-Hodgkin lymphomas (T-NHLs). (bvsalud.org)
  • In vivo evaluation of the bystander effect in mouse models demonstrated that for effective therapy, at least 1% of tumor cells need to be delivered with TK-NTR-encoding MCs. (regenerativemedicine.net)
  • RNA-seq analyses revealed that T. versicolor oxalate production from the TCA/glyoxylate cycle was down-regulated, and conversely, genes encoding oxalate and formate metabolism enzymes were up-regulated. (frontiersin.org)
  • In this study, delivery vehicles comprised of microvesicles loaded with engineered minicircle (MC) DNA that encodes prodrug converting enzymes were developed as a cancer therapy in mammary carcinoma models. (regenerativemedicine.net)
  • Invitrogen Anti-ATP Citrate Lyase Polyclonal, Catalog # PA5-29497. (siderac.com)
  • Citrate is central to mitochondrial metabolism and respiration and plays fundamental activities in the cytosol, serving as a metabolic substrate, an allosteric enzymatic regulator and, as the source of Acetyl-Coenzyme A, also as an epigenetic modifier. (nih.gov)
  • Dysfunctional autoimmune Tregs display pro-inflammatory features and altered mitochondrial metabolism, but contributing factors remain elusive. (bvsalud.org)
  • In addition, it revealed enhancement of both H3ace and H4ace binding on the promoter region of Rela , as well as positive correlations between Rela and genes encoding histone acetyltransferases (HATs) including CREB-binding protein (CBP) and E1A-associated protein p300 (EP300). (frontiersin.org)
  • However, cellular citrate remains critically low in mutant Th17 cells, which interferes with oxidative phosphorylation (OXPHOS), lipid synthesis, and histone acetylation, crucial for transcription of Th17 signature genes. (bvsalud.org)
  • This is in contrast to Sordaria macrospora, in which fruiting body formation is initiated but maturation is defective in an ATP-citrate lyase mutant. (siderac.com)
  • In living organisms, succinic acid takes the form of an anion, succinate, which has multiple biological roles as a metabolic intermediate being converted into fumarate by the enzyme succinate dehydrogenase in complex 2 of the electron transport chain which is involved in making ATP, and as a signaling molecule reflecting the cellular metabolic state. (wikipedia.org)
  • Alternatively spliced transcript variants encoding different isoforms have been described. (wildpalm.net)
  • This strategy relies on isotope encoded chemical cross-linkers that have the same molecular mass yet produce unique and specific isotope signatures upon fragmentation in the mass spectrometer which can be used for quantitative analysis of cross-linked peptides. (tuberculosistest.net)
  • The mitochondrial citrate/isocitrate carrier, CIC, has been shown to play an important role in a growing list of human diseases. (nih.gov)
  • Here, we show that PDH is essential for the generation of a glucose-derived citrate pool needed for Th17 cell proliferation, survival, and effector function. (bvsalud.org)
  • The hypoxia-inducible factors (HIF) act as hypoxia sensors that orchestrate a coordinated response increasing the pro-survival and pro-invasive phenotype of cancer cells, and determine a broad metabolic rewiring. (mdpi.com)
  • E. coli-derived human ATP citrate lyase recombinant protein (Position: M1-I180). (thermofisher.com)
  • Human(47) Summary: ATP citrate lyase is the primary enzyme responsible for the synthesis of cytosolic acetyl-CoA in many tissues. (siderac.com)
  • Western blot analysis of ATP citrate lyase using A) 30 µg PC-12 whole cell lysate and B) 30 µg Rat2 whole cell lysate. (siderac.com)
  • S55746 is a potent and selective inhibitor of the anti-apoptotic protein B-cell lymphoma 2 (Bcl-2), with potential pro-apoptotic and antineoplastic activities. (csnpharm.cn)
  • In some embodiments, the methylotrophic yeast cell further includes a nucleic acid molecule that includes at least one heterologous nucleic acid encoding a polypeptide operably linked to at least one methanol-inducible promoter element. (justia.com)
  • CIC belongs to a large family of nuclear-encoded mitochondrial transporters that serve the fundamental function of allowing the transit of ions and metabolites through the impermeable mitochondrial membrane. (nih.gov)