Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 13

Publication Record

Connections

Regulation of leukocyte function by citric acid cycle intermediates.
Patil NK, Bohannon JK, Hernandez A, Patil TK, Sherwood ER
(2019) J Leukoc Biol 106: 105-117
MeSH Terms: Animals, Citric Acid, Citric Acid Cycle, Fumarates, Humans, Leukocytes, Reactive Oxygen Species, Succinates, Succinic Acid
Show Abstract · Added March 18, 2020
Cellular metabolism is a means of generating ATP to provide energy for key cellular functions. However, recent research shows that citric acid cycle intermediates target vital cellular functions of the innate immune system. Succinate, itaconate, citrate, and fumarate have been shown to mediate or regulate important myeloid cell functions during infection and inflammation. This review covers the regulatory functions of citric acid cycle intermediates in myeloid cells and discusses potential translational applications, key mechanistic questions, and future research directions.
©2019 Society for Leukocyte Biology.
0 Communities
2 Members
0 Resources
9 MeSH Terms
Open-Source Automated Parahydrogen Hyperpolarizer for Molecular Imaging Using (13)C Metabolic Contrast Agents.
Coffey AM, Shchepin RV, Truong ML, Wilkens K, Pham W, Chekmenev EY
(2016) Anal Chem 88: 8279-88
MeSH Terms: Animals, Automation, Carbon Isotopes, Catalysis, Contrast Media, Hydrogen, Lactic Acid, Magnetic Resonance Imaging, Magnetic Resonance Spectroscopy, Mice, Mice, Nude, Software, Succinates, Water
Show Abstract · Added March 21, 2018
An open-source hyperpolarizer producing (13)C hyperpolarized contrast agents using parahydrogen induced polarization (PHIP) for biomedical and other applications is presented. This PHIP hyperpolarizer utilizes an Arduino microcontroller in conjunction with a readily modified graphical user interface written in the open-source processing software environment to completely control the PHIP hyperpolarization process including remotely triggering an NMR spectrometer for efficient production of payloads of hyperpolarized contrast agent and in situ quality assurance of the produced hyperpolarization. Key advantages of this hyperpolarizer include: (i) use of open-source software and hardware seamlessly allowing for replication and further improvement as well as readily customizable integration with other NMR spectrometers or MRI scanners (i.e., this is a multiplatform design), (ii) relatively low cost and robustness, and (iii) in situ detection capability and complete automation. The device performance is demonstrated by production of a dose (∼2-3 mL) of hyperpolarized (13)C-succinate with %P13C ∼ 28% and 30 mM concentration and (13)C-phospholactate at %P13C ∼ 15% and 25 mM concentration in aqueous medium. These contrast agents are used for ultrafast molecular imaging and spectroscopy at 4.7 and 0.0475 T. In particular, the conversion of hyperpolarized (13)C-phospholactate to (13)C-lactate in vivo is used here to demonstrate the feasibility of ultrafast multislice (13)C MRI after tail vein injection of hyperpolarized (13)C-phospholactate in mice.
0 Communities
1 Members
0 Resources
14 MeSH Terms
A 5-hydroxytryptamine receptor antagonist, sarpogrelate, reduces renal tubulointerstitial fibrosis by suppressing PAI-1.
Hamasaki Y, Doi K, Maeda-Mamiya R, Ogasawara E, Katagiri D, Tanaka T, Yamamoto T, Sugaya T, Nangaku M, Noiri E
(2013) Am J Physiol Renal Physiol 305: F1796-803
MeSH Terms: Adenine, Animals, Cells, Cultured, Disease Models, Animal, Fatty Acid-Binding Proteins, Fibrosis, In Vitro Techniques, Kidney Tubules, Male, Mice, Mice, Inbred C57BL, Mice, Transgenic, Nephritis, Interstitial, Plasminogen Activator Inhibitor 1, Regional Blood Flow, Serotonin, Serotonin Antagonists, Succinates, Transforming Growth Factor beta1, Up-Regulation
Show Abstract · Added February 11, 2016
A selective 5-hydroxytryptamine (5-HT) 2A receptor antagonist sarpogrelate (SG) blocks serotonin-induced platelet aggregation. It has been used clinically for the treatment of peripheral arterial disease. SG might be able to improve chronic ischemia, which contributes to renal fibrosis progression by maintaining renal microcirculation. This study investigated whether SG suppresses renal fibrosis. C57BL/6 mice fed a 0.2% adenine-containing diet for 6 wk developed severe tubulointerstitial fibrosis with kidney dysfunction. Subsequent SG treatment (30 mg·kg(-1)·day(-1)) for 4 wk improved these changes significantly by increasing peritubular blood flow in the fibrotic area, as evaluated by intravital microscopy and decreasing fibrin deposition. Urinary L-type fatty acid-binding protein, up-regulated by renal hypoxia, was also reduced by SG. Additionally, results showed that mRNA expression of plasminogen activator inhibitor-1 (PAI-1), which is known to promote fibrosis by mediating and enhancing transforming growth factor (TGF)-β1 signaling, was suppressed by SG treatment in the kidney. In vitro experiments using cultured murine proximal tubular epithelial (mProx) cells revealed that incubation with TGF-β1 and 5-HT increased PAI-1 mRNA expression; SG significantly reduced it. In conclusion, SG reduces renal fibrosis not only by the antithrombotic effect of maintaining peritubular blood flow but also by suppressing PAI-1 expression in renal tubular cells.
0 Communities
1 Members
0 Resources
20 MeSH Terms
The neuromediator glutamate, through specific substrate interactions, enhances mitochondrial ATP production and reactive oxygen species generation in nonsynaptic brain mitochondria.
Panov A, Schonfeld P, Dikalov S, Hemendinger R, Bonkovsky HL, Brooks BR
(2009) J Biol Chem 284: 14448-56
MeSH Terms: Adenosine Triphosphate, Animals, Brain, Cell Respiration, Glutamic Acid, Hydrogen Peroxide, Male, Mitochondria, Mitochondria, Heart, Models, Biological, Neurons, Oxidation-Reduction, Pyruvic Acid, Rats, Rats, Sprague-Dawley, Reactive Oxygen Species, Serum Albumin, Bovine, Substrate Specificity, Succinates, Synapses
Show Abstract · Added February 17, 2016
The finding that upon neuronal activation glutamate is transported postsynaptically from synaptic clefts and increased lactate availability for neurons suggest that brain mitochondria (BM) utilize a mixture of substrates, namely pyruvate, glutamate, and the tricarboxylic acid cycle metabolites. We studied how glutamate affected oxidative phosphorylation and reactive oxygen species (ROS) production in rat BM oxidizing pyruvate + malate or succinate. Simultaneous oxidation of glutamate + pyruvate + malate increased state 3 and uncoupled respiration by 52 and 71%, respectively. The state 4 ROS generation increased 100% over BM oxidizing pyruvate + malate and 900% over that of BM oxidizing glutamate + malate. Up to 70% of ROS generation was associated with reverse electron transport. These effects of pyruvate + glutamate + malate were observed only with BM and not with liver or heart mitochondria. The effects of glutamate + pyruvate on succinate-supported respiration and ROS generation were not organ-specific and depended only on whether mitochondria were isolated with or without bovine serum albumin. With the non-bovine serum albumin brain and heart mitochondria oxidizing succinate, the addition of pyruvate and glutamate abrogated inhibition of Complex II by oxaloacetate. We conclude that (i) during neuronal activation, simultaneous oxidation of glutamate + pyruvate temporarily enhances neuronal mitochondrial ATP production, and (ii) intrinsic inhibition of Complex II by oxaloacetate is an inherent mechanism that protects against ROS generation during reverse electron transport.
0 Communities
1 Members
0 Resources
20 MeSH Terms
Human immunodeficiency virus type 1 resistance to the small molecule maturation inhibitor 3-O-(3',3'-dimethylsuccinyl)-betulinic acid is conferred by a variety of single amino acid substitutions at the CA-SP1 cleavage site in Gag.
Zhou J, Chen CH, Aiken C
(2006) J Virol 80: 12095-101
MeSH Terms: Amino Acid Substitution, Anti-HIV Agents, Cell Line, Tumor, Drug Resistance, Viral, Gene Products, gag, HIV-1, Humans, Mutagenesis, Succinates, Triterpenes, Virus Assembly, Virus Replication
Show Abstract · Added February 19, 2015
The compound 3-O-(3',3'-dimethylsuccinyl)-betulinic acid (DSB) potently and specifically inhibits human immunodeficiency virus type 1 (HIV-1) replication by delaying the cleavage of the CA-SP1 junction in Gag, leading to impaired maturation of the viral core. In this study, we investigated HIV-1 resistance to DSB by analyzing HIV-1 mutants encoding a variety of individual amino acid substitutions in the CA-SP1 cleavage site. Three of the substitutions were lethal to HIV-1 replication owing to a deleterious effect on particle assembly. The remaining mutants exhibited a range of replication efficiencies; however, each mutant was capable of replicating in the presence of concentrations of DSB that effectively inhibited wild-type HIV-1. Mutations conferring resistance to DSB also led to impaired binding of the compound to immature HIV-1 virions and loss of DSB-mediated inhibition of cleavage of Gag. Surprisingly, two of the DSB-resistant mutants retained an intermediate ability to bind the compound, suggesting that binding of DSB to immature HIV-1 particles may not be sufficient for antiviral activity. Overall, our results indicate that Gag amino acids L363 and A364 are critical for inhibition of HIV-1 replication by DSB and suggest that these residues form key contacts with the drug in the context of the assembling HIV-1 particle. These results have implications for the design of and screening for novel inhibitors of HIV-1 maturation.
0 Communities
1 Members
0 Resources
12 MeSH Terms
The sequence of the CA-SP1 junction accounts for the differential sensitivity of HIV-1 and SIV to the small molecule maturation inhibitor 3-O-{3',3'-dimethylsuccinyl}-betulinic acid.
Zhou J, Chen CH, Aiken C
(2004) Retrovirology 1: 15
MeSH Terms: Animals, Anti-HIV Agents, Base Sequence, CD4-Positive T-Lymphocytes, Cell Line, DNA Primers, Drug Resistance, Viral, HIV-1, Humans, Kidney, Pregnancy-Specific beta 1-Glycoproteins, Simian Immunodeficiency Virus, Succinates, Triterpenes, Virus Replication
Show Abstract · Added February 19, 2015
BACKGROUND - Despite the effectiveness of currently available antiretroviral therapies in the treatment of HIV-1 infection, a continuing need exists for novel compounds that can be used in combination with existing drugs to slow the emergence of drug-resistant viruses. We previously reported that the small molecule 3-O-{3',3'-dimethylsuccinyl}-betulinic acid (DSB) specifically inhibits HIV-1 replication by delaying the processing of the CA-SP1 junction in Pr55Gag. By contrast, SIVmac239 replicates efficiently in the presence of high concentrations of DSB. To determine whether sequence differences in the CA-SP1 junction can fully account for the differential sensitivity of HIV-1 and SIV to DSB, we engineered mutations in this region of two viruses and tested their sensitivity to DSB in replication assays using activated human primary CD4+ T cells.
RESULTS - Substitution of the P2 and P1 residues of HIV-1 by the corresponding amino acids of SIV resulted in strong resistance to DSB, but the mutant virus replicated with reduced efficiency. Conversely, replication of an SIV mutant containing three amino acid substitutions in the CA-SP1 cleavage site was highly sensitive to DSB, and the mutations resulted in delayed cleavage of the CA-SP1 junction in the presence of the drug.
CONCLUSIONS - These results demonstrate that the CA-SP1 junction in Pr55Gag represents the primary viral target of DSB. They further suggest that the therapeutic application of DSB will be accompanied by emergence of mutant viruses that are highly resistant to the drug but which exhibit reduced fitness relative to wild type HIV-1.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Cloning and functional characterization of a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain.
Pajor AM, Gangula R, Yao X
(2001) Am J Physiol Cell Physiol 280: C1215-23
MeSH Terms: Amino Acid Sequence, Animals, Brain, Carrier Proteins, Cloning, Molecular, Consensus Sequence, Female, Fishes, Gene Library, Humans, Kinetics, Membrane Potentials, Membrane Transport Proteins, Mice, Molecular Sequence Data, Oocytes, Rats, Recombinant Proteins, Reverse Transcriptase Polymerase Chain Reaction, Sequence Alignment, Sequence Homology, Amino Acid, Substrate Specificity, Succinates, Symporters, Xenopus laevis
Show Abstract · Added April 7, 2010
Neurons contain a high-affinity Na(+)/dicarboxylate cotransporter for absorption of neurotransmitter precursor substrates, such as alpha-ketoglutarate and malate, which are subsequently metabolized to replenish pools of neurotransmitters, including glutamate. We have isolated the cDNA coding for a high-affinity Na(+)/dicarboxylate cotransporter from mouse brain, called mNaDC-3. The mRNA coding for mNaDC-3 is found in brain and choroid plexus as well as in kidney and liver. The mNaDC-3 transporter has a broad substrate specificity for dicarboxylates, including succinate, alpha-ketoglutarate, fumarate, malate, and dimethylsuccinate. The transport of citrate is relatively insensitive to pH, but the transport of succinate is inhibited by acidic pH. The Michaelis-Menten constant for succinate in mNaDC-3 is 140 microM in transport assays and 16 microM at -50 mV in two-electrode voltage clamp assays. Transport is dependent on sodium, although lithium can partially substitute for sodium. In conclusion, mNaDC-3 likely codes for the high-affinity Na(+)/dicarboxylate cotransporter in brain, and it has some unusual electrical properties compared with the other members of the family.
0 Communities
1 Members
0 Resources
25 MeSH Terms
Oxidation of C-1 compounds by Pseudomonas sp. MS.
Kung HF, Wagner C
(1970) Biochem J 116: 357-65
MeSH Terms: Amines, Amino Acids, Carbon Dioxide, Carbon Isotopes, Culture Media, Enzyme Induction, Ethanol, Formaldehyde, Formates, Hexoses, Lactates, Methane, Methanol, Methotrexate, Oxidoreductases, Pseudomonas, Pyruvates, Succinates
Show Abstract · Added January 20, 2015
Pseudomonas sp. MS is capable of growth on a number of compounds containing only C(1) groups. They include trimethylsulphonium salts, methylamine, dimethylamine and trimethylamine. Although formaldehyde and formate will not support growth they are rapidly oxidized by intact cells. Methanol neither supports growth nor is oxidized. A particulate fraction of the cell oxidizes methylamine to carbon dioxide in the absence of any external electron acceptor. Formaldehyde and formate are more slowly oxidized to carbon dioxide by the particulate fraction, although they do not appear to be free intermediates in the oxidation of methylamine. Soluble NAD-linked formaldehyde dehydrogenase and formate dehydrogenase are also present. The particulate methylamine oxidase is induced by growth on methylamine, dimethylamine and trimethylamine, whereas the soluble formaldehyde dehydrogenase and formate dehydrogenase are induced by trimethylsulphonium nitrate as well as the aforementioned amines.
0 Communities
1 Members
0 Resources
18 MeSH Terms
Malabsorption of thiamin in folate-deficient rats.
Howard L, Wagner C, Schenker S
(1974) J Nutr 104: 1024-32
MeSH Terms: Animals, Biological Transport, Biological Transport, Active, Duodenum, Erythrocytes, Folic Acid, Folic Acid Deficiency, Ileum, Intestine, Small, Jejunum, Liver, Malabsorption Syndromes, Rats, Succinates, Sulfathiazoles, Thiamine, Time Factors
Added January 20, 2015
0 Communities
1 Members
0 Resources
17 MeSH Terms
The metabolism of lactate and pyruvate by Pseudomonas AM1.
Salem AR, Wagner C, Hacking AJ, Quayle JR
(1973) J Gen Microbiol 76: 375-88
MeSH Terms: Carbon Isotopes, Cell-Free System, Chromatography, Thin Layer, Culture Media, Ethanol, Glycolates, Glyoxylates, Ketone Oxidoreductases, Lactates, Ligases, Malate Dehydrogenase, Methanol, Mutation, Oxo-Acid-Lyases, Phosphoenolpyruvate, Phosphoenolpyruvate Carboxykinase (GTP), Phosphopyruvate Hydratase, Phosphotransferases, Pseudomonas, Pyruvate Kinase, Pyruvates, Spectrophotometry, Succinates
Added January 20, 2015
0 Communities
1 Members
0 Resources
23 MeSH Terms