Individual and combined inhibitory effects of methanol and toluene on acetyl-CoA synthetase expression level of acetoclastic methanogen, Methanosaeta concilii

Abstract Diabetes mellitus is a complex metabolic disease around the world that is characterized by hyperglycemia resulting from impaired insulin secretion, insulin action, or both. MicroRNA-29a is an important regulator of insulin signaling and gluconeogenesis pathways through IRS2, PI3K and PEPCK expressions which up regulates in Diabetes. Morin is a substantial bioflavonoid which has insulin mimetic effect, and interacting with nucleic acids and proteins. In this study HepG2 cells, were exposed to high glucose to induce diabetic condition. We have determined whether high glucose stimulation might promotes miR-29a expression level in HepG2 cells and subsequently evaluated the Morin treatment effects on this state. In HepG2 cells, high glucose increases miR-29a expression level and decreases its target genes, IRS2 and PI3K expression, and increases associated downstream gene in gluconeogenic pathway, PEPCK. Morin treatment down regulates miR-29a expression level and improves insulin signaling and glucose metabolism. To confirm the inhibitory effects of Morin on miR-29a, we have transfected cells with mimic and inhibitor-miR-29a. This study for the first time identifies that Morin improves diabetic condition through down regulation of the miR-29a level, and suggest that this new inhibitor of miR-29a may be a useful biomedicine to treat diabetes.

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THE FORMATION OF ACETOACETATE FROM ACETYL COENZYME A, MALONYL COENZYME A, AND PYRUVATE BY WASHED MITOCHONDRIA ISOLATED FROM GUINEA PIG LIVER

Canadian Journal of Biochemistry and Physiology ◽

10.1139/y63-227 ◽

1963 ◽

Vol 41 (1) ◽

pp. 1997-2011

Author(s):

F. Sauer

Keyword(s):

Guinea Pig ◽

Coenzyme A ◽

Inhibitory Effects ◽

Significant Extent ◽

Acetyl Coa ◽

Pig Liver ◽

Malonyl Coa ◽

Binding Agents ◽

Guinea Pig Liver ◽

Tracer Experiments

Washed mitochondria isolated from guinea pig liver were capable of synthesizing acetoacetate from pyruvate. Both acetyl-CoA and malonyl-CoA were incorporated into acetoacetate in the presence of pyruvate. However, without pyruvate, only acetyl-CoA was incorporated to any significant extent. Tracer experiments indicated that although malonyl-CoA was incorporated into acetoacetate, increased acetoacetate synthesis in the presence of pyruvate plus malonyl-CoA resulted primarily from increased pyruvate incorporation.The results of the present experiments indicated that a CO2fixation step was involved in the conversion of pyruvate to acetoacetate. Evidence in favor of this was based on the inhibitory effects of avidin (with partial reversal by biotin), stimulation with increasing bicarbonate concentration, and increased acetoacetate synthesis in the presence of malonyl-CoA.Sulphydryl binding agents completely inhibited acetoacetate synthesis from pyruvate. In the formation of acetoacetate, carbon atom 1 of pyruvate was eliminated. This indicated that pyruvate was converted into an active 2-carbon unit.

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Effects of dichloroacetate on the metabolism of glucose, pyruvate, acetate, 3-hydroxybutyrate and palmitate in rat diaphragm and heart muscle in vitro and on extraction of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo

Biochemical Journal ◽

10.1042/bj1341067 ◽

1973 ◽

Vol 134 (4) ◽

pp. 1067-1081 ◽

Cited By ~ 88

Author(s):

Anthony McAllister ◽

S. P. Allison ◽

Philip J. Randle

Keyword(s):

Fatty Acids ◽

Free Fatty Acids ◽

Plasma Free Fatty Acid ◽

Diabetic Rats ◽

Inhibitory Effects ◽

Acetyl Coa ◽

Citrate Concentration ◽

Lactate And Pyruvate

1. The extractions of glucose, lactate, pyruvate and free fatty acids by dog heart in vivo were calculated from measurements of their arterial and coronary sinus blood concentration. Elevation of plasma free fatty acid concentrations by infusion of intralipid and heparin resulted in increased extraction of free fatty acids and diminished extractions of glucose, lactate and pyruvate by the heart. It is suggested that metabolism of free fatty acids by the heart in vivo, as in vitro, may impair utilization of these substrates. These effects of elevated plasma free fatty acid concentrations on extractions by the heart in vivo were reversed by injection of dichloroacetate, which also improved extraction of lactate and pyruvate by the heart in vivo in alloxan diabetes. 2. Sodium dichloroacetate increased glucose oxidation and pyruvate oxidation in hearts from fed normal or alloxan-diabetic rats perfused with glucose and insulin. Dichloroacetate inhibited oxidation of acetate and 3-hydroxybutyrate and partially reversed inhibitory effects of these substrates on the oxidation of glucose. In rat diaphragm muscle dichloroacetate inhibited oxidation of acetate, 3-hydroxybutyrate and palmitate and increased glucose oxidation and pyruvate oxidation in diaphragms from alloxan-diabetic rats. Dichloroacetate increased the rate of glycolysis in hearts perfused with glucose, insulin and acetate and evidence is given that this results from a lowering of the citrate concentration within the cell, with a consequent activation of phosphofructokinase. 3. In hearts from normal rats perfused with glucose and insulin, dichloroacetate increased cell concentrations of acetyl-CoA, acetylcarnitine and glutamate and lowered those of aspartate and malate. In perfusions with glucose, insulin and acetate, dichloroacetate lowered the cell citrate concentration without lowering the acetyl-CoA or acetylcarnitine concentrations. Measurements of specific radioactivities of acetyl-CoA, acetylcarnitine and citrate in perfusions with [1-14C]acetate indicated that dichloroacetate lowered the specific radio-activity of these substrates in the perfused heart. Evidence is given that dichloroacetate may not be metabolized by the heart to dichloroacetyl-CoA or dichloroacetylcarnitine or citrate or CO2. 4. We suggest that dichloroacetate may activate pyruvate dehydrogenase, thus increasing the oxidation of pyruvate to acetyl-CoA and acetylcarnitine and the conversion of acetyl-CoA into glutamate, with consumption of aspartate and malate. Possible mechanisms for the changes in cell citrate concentration and for inhibitory effects of dichloroacetate on the oxidation of acetate, 3-hydroxybutyrate and palmitate are discussed.

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Coenzyme A is a potent inhibitor of acetyl-CoA carboxylase from rat epididymal fat-pads

Biochemical Journal ◽

10.1042/bj2830035 ◽

1992 ◽

Vol 283 (1) ◽

pp. 35-38 ◽

Cited By ~ 8

Author(s):

S K Moule ◽

N J Edgell ◽

A C Borthwick ◽

R M Denton

Keyword(s):

Potent Inhibitor ◽

Ion Exchange Chromatography ◽

Exchange Chromatography ◽

Acetyl Coa Carboxylase ◽

Inhibitory Effects ◽

Fat Pad ◽

Maximal Inhibition ◽

Acetyl Coa ◽

Epididymal Fat ◽

Fat Pads

Rat epididymal fat-pad extracts have previously been shown to contain an insulin-stimulated acetyl-CoA carboxylase kinase, which is co-eluted from Mono Q ion-exchange chromatography with a potent inhibitor of acetyl-CoA carboxylase [Borthwick, Edgell & Denton (1990) Biochem. J. 270, 795-801]. A variety of tests, including reactivity with thiol reagents, identify this inhibitor as CoA. Inhibition requires the presence of MgATP, but is independent of any phosphorylation of the enzyme. The effect is complete in about 5 min and is associated with depolymerization of acetyl-CoA carboxylase. Half-maximal inhibition is observed at about 40 nM-CoA. The inhibitory effects of CoA can be partially reversed by incubation with citrate and more fully overcome by treatment of the enzyme with the insulin-stimulated acetyl-CoA carboxylase kinase.

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THE FORMATION OF ACETOACETATE FROM ACETYL COENZYME A, MALONYL COENZYME A, AND PYRUVATE BY WASHED MITOCHONDRIA ISOLATED FROM GUINEA PIG LIVER

Canadian Journal of Biochemistry and Physiology ◽

10.1139/o63-227 ◽

1963 ◽

Vol 41 (9) ◽

pp. 1997-2011

Author(s):

F. Sauer

Keyword(s):

Guinea Pig ◽

Coenzyme A ◽

Inhibitory Effects ◽

Significant Extent ◽

Acetyl Coa ◽

Pig Liver ◽

Malonyl Coa ◽

Binding Agents ◽

Guinea Pig Liver ◽

Tracer Experiments

Washed mitochondria isolated from guinea pig liver were capable of synthesizing acetoacetate from pyruvate. Both acetyl-CoA and malonyl-CoA were incorporated into acetoacetate in the presence of pyruvate. However, without pyruvate, only acetyl-CoA was incorporated to any significant extent. Tracer experiments indicated that although malonyl-CoA was incorporated into acetoacetate, increased acetoacetate synthesis in the presence of pyruvate plus malonyl-CoA resulted primarily from increased pyruvate incorporation.The results of the present experiments indicated that a CO2fixation step was involved in the conversion of pyruvate to acetoacetate. Evidence in favor of this was based on the inhibitory effects of avidin (with partial reversal by biotin), stimulation with increasing bicarbonate concentration, and increased acetoacetate synthesis in the presence of malonyl-CoA.Sulphydryl binding agents completely inhibited acetoacetate synthesis from pyruvate. In the formation of acetoacetate, carbon atom 1 of pyruvate was eliminated. This indicated that pyruvate was converted into an active 2-carbon unit.

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Different sites of inhibition of carnitine palmitoyltransferase by malonyl-CoA, and by acetyl-CoA and CoA, in human skeletal muscle

Biochemical Journal ◽

10.1042/bj2450205 ◽

1987 ◽

Vol 245 (1) ◽

pp. 205-209 ◽

Cited By ~ 25

Author(s):

S Zierz ◽

A G Engel

Keyword(s):

Skeletal Muscle ◽

Human Subjects ◽

Fold Increase ◽

Inhibitory Effect ◽

Carnitine Palmitoyltransferase ◽

Inhibitory Effects ◽

Acetyl Coa ◽

Malonyl Coa ◽

Normal Human ◽

Triton X

The inhibition of carnitine palmitoyltransferase (CPT, EC 2.3.1.21) by malonyl-CoA, acetyl-CoA and free CoA was studied in sonicated skeletal-muscle homogenates from normal human subjects and from five patients with a mutant CPT [Zierz & Engel (1985) Eur. J. Biochem. 149, 207-214]. (1) Malonyl-CoA, acetyl-CoA and CoA were competitive inhibitors of CPT with palmitoyl-CoA. (2) Acetyl-CoA and CoA inhibited normal and mutant CPT to the same degree, whereas malonyl-CoA inhibited mutant CPT more than normal CPT. (3) Triton X-100 abolished the inhibition of normal CPT by malonyl-CoA, but not by acetyl-CoA or CoA. Triton X-100 by itself caused loss of activity of the mutant CPT. (4) In the concentration range 0.1-0.4 mM, the inhibitory effects of any two of the three inhibitors were synergistic. (5) The inhibitory constants (Ki) for acetyl-CoA and CoA were close to 45 microM. The Ki for malonyl-CoA was 200-fold lower, or 0.22 microM. Addition of 40 microM-acetyl-CoA or CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. Addition of 20 microM-CoA resulted in a 3-fold increase in the Ki for acetyl-CoA. (6) The findings indicate that acetyl-CoA and CoA can inhibit CPT at the catalytic site or a nearby site which is different from that at which malonyl-CoA inhibits CPT. (7) The fact that small changes in the concentration of acetyl-CoA and CoA can antagonize the inhibitory effect of malonyl-CoA suggests that these compounds could modulate the inhibition of CPT by malonyl-CoA.

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Identification of hub-genes, lncRNAs, and skin cancer inducer genes through meta-analysis of Hidradenitis Suppurativa disease transcriptome data.

10.21203/rs.3.rs-903999/v1 ◽

2021 ◽

Author(s):

Mehrdad Shahbazi ◽

Nikta Ziaei

Keyword(s):

Gene Ontology ◽

Skin Cancer ◽

Hidradenitis Suppurativa ◽

Expression Level ◽

Formyl Peptide Receptor ◽

Molecular Response ◽

Transcriptome Data ◽

Inhibitory Effects ◽

Hub Genes ◽

Chemokine Ligand

Abstract This research is aimed to explore the molecular response of the skin cells to Hidradenitis Suppurativa (HS). Microarray transcriptome data for patients with HS, merged and employed to identify the differentially expressed genes (DEGs), gene ontology (GO), and long non-coding RNAs (lncRNAs). A protein-protein interaction network, and consequently, a co-expression network, was constructed for the essential genes. The key genes' clinical relevance was also established by survival analysis, relative expression level, immunohistochemistry, and immune infiltration correlation analysis. Finally, potential herbal ingredients with inhibitory effects on cancer inducer proteins were characterized using the Traditional Chinese Medicine (TCMD) database. The chemokine signaling pathway was the gene ontology of the most significant cluster found by clusterONE. Myocardial Infarction Associated Transcript (MIAT) and RNA Polymerase II Subunit J4, Pseudogene (POLR2J4) are the predicted lncRNAs for up-and down-regulated genes. Interleukin 6 (IL6), Formyl Peptide Receptor 2 (FPR2), C-X-C Motif Chemokine Ligand 10 (CXCL10), C-C Motif Chemokine Receptor 7 (CCR7), and C-C Motif Chemokine Ligand 5 (CCL5) genes were predicted as hub-genes. Tryptophan 2,3-Dioxygenase (TDO2), Serpin Family B Member 4 (SERPINB4), and Matrix Metallopeptidase 3 (MMP3) were demonstrated to be potential cancer inducers due to their high expression level in HS disease. These genes also were positively correlated with dendritic cells, T cell CD4+, monocytes, and neutrophils in the skin cancer microenvironment. Piceatannol, Salicylic acid, and magnolol herbal ingredients were predicted as potential compounds with inhibitory effects on SERPIN B4, MMP3, and TDO2, respectively. The output of the present study will aid in a better understanding of the HS disease and consequent cancer induction mechanism.

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Dietary supplemental chromium and niacin influence the growth performance and fat deposition in lambs

Animal Production Science ◽

10.1071/an18717 ◽

2020 ◽

Vol 60 (5) ◽

pp. 618

Author(s):

K. Hashemian ◽

M. A. Norouzian ◽

A. Mohammadi-Sangcheshmeh

Keyword(s):

Meat Quality ◽

Low Density Lipoprotein ◽

Density Lipoprotein ◽

Fat Deposition ◽

Feed Additives ◽

Expression Level ◽

Acetyl Coa Carboxylase ◽

Acetyl Coa ◽

Fat Tail ◽

Chromium Methionine

Context Nowadays fat is an unpopular constituent of meat for consumers and therefore, a decrease in fat-tail size is often desirable for producers. Feed additives like chromium (Cr) and niacin (B3) have been reported to improve meat quality in beef and dairy cattle. However, their effect on meat quality and performance of fat-tail breeds of finishing lambs is unknown. Aim The aim of this study was to investigate the effect of supplemental chromium (Cr) and niacin (B3) on performance and fat deposition of carcass of finishing lambs. Methods Twenty male Zandi lambs (23.7 ± 0.73 kg) were allocated into one of four treatments: (1) control; (2) 300 µg/ kg DM Cr as chromium methionine; (3) 200 mg/kg DM B3 as rumen-protected niacin; and (4) 300 µg/ kg DM Cr as chromium methionine + 200 mg/kg DM B3 as rumen-protected niacin. Key results Chromium and B3 supplementation decreased blood glucose, insulin, triglycerides and low-density lipoprotein levels (P < 0.05). Lambs fed diet supplemented with B3 consumed more feed with a higher growth (P < 0.05) compared with other groups. There were no significant differences in feed efficiency, hot carcass weight, and dressing percentage among experimental groups. However, there was a decrease in the subcutaneous, abdominal, tail and total carcass fat in Cr supplemented lambs (P < 0.01) compared with other experimental groups. The expression level of acetyl CoA carboxylase 1 (ACC1) and diglyceride acyltransferase 2 (DGAT2) genes was lower in Cr groups of lambs compared with other groups (P < 0.05). Conclusions These results indicated that organic Cr supplementation improved meat quality by reducing fat accumulation, whereas B3 supplementation resulted in higher growth rate and feed intake. Implications Results showed that chromium supplementation reduces expression level of acetyl CoA carboxylase 1 and diglyceride acyltransferase 2 genes resulting in lower level of subcutaneous, abdominal, tail and total carcass fat of finishing lambs.

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MicroRNA-150 Inhibits Cell Invasion and Migration and Is Downregulated in Human Osteosarcoma

Cytogenetic and Genome Research ◽

10.1159/000437379 ◽

2015 ◽

Vol 146 (2) ◽

pp. 124-135 ◽

Cited By ~ 11

Author(s):

Xiao Li ◽

Li Chen ◽

Wei Wang ◽

Fan-Bin Meng ◽

Ren-Tao Zhao ◽

...

Keyword(s):

Cell Proliferation ◽

Cell Apoptosis ◽

Expression Level ◽

Luciferase Reporter ◽

Inhibitory Effects ◽

Invasion And Metastasis ◽

Invasion And Migration ◽

Protein Levels ◽

Mg63 Cells ◽

And Migration

miR-150 expression in osteosarcoma (OS) cell lines and human osteoblast cells was detected, and OS cell models were transfected with exogenous miR-150 to investigate its role in cell proliferation, invasion, and apoptosis. Our results showed that miR-150 expression in OS cells (MG63, Saos-2, SOSP-9607, and U2OS) was significantly lower compared to the osteoblast hFOB1.19 cell line (all p < 0.01). The expression level of miR-150 in MG63 cells that were transfected with exogenous miR-150 mimics was markedly upregulated, while the miR-150 expression level in the inhibitor group was significantly downregulated (both p < 0.01). Similar results were also found in SOSP-9607 cells. Importantly, exogenous miR-150 expression stimulated cell apoptosis and inhibited proliferation, invasion, and migration. A luciferase reporter assay displayed that miR-150 also regulated Sp1 expression by targeting its 3′-UTR, and qRT-PCR and Western blotting showed that elevated levels of miR-150 may reduce Sp1 protein expression. The mRNA and protein levels of Sp1 were upregulated after transfection with a Sp1-expression plasmid and partially reversed the inhibitory effects of miR-150 on cell proliferation, invasion, and metastasis in MG63 and SOSP-9607 cells, as well as promoted cell apoptosis. In conclusion, miR-150 inhibits cell proliferation, invasion, and metastasis and stimulates cell apoptosis by regulating the expression of Sp1. Therefore, miR-150 may be a potential clinical target for the treatment of OS patients.

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