scholarly journals An O-GlcNAcylomic Approach Reveals ACLY as a Potential Target in Sepsis in the Young Rat

2021 ◽  
Vol 22 (17) ◽  
pp. 9236
Author(s):  
Manon Denis ◽  
Thomas Dupas ◽  
Antoine Persello ◽  
Justine Dontaine ◽  
Laurent Bultot ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Young Population ◽  
Post Translational Modification ◽  
Atp Citrate Lyase ◽  
E Coli ◽  
Citrate Lyase ◽  
Old Rats ◽  
Young Rat

Sepsis in the young population, which is particularly at risk, is rarely studied. O-GlcNAcylation is a post-translational modification involved in cell survival, stress response and metabolic regulation. O-GlcNAc stimulation is beneficial in adult septic rats. This modification is physiologically higher in the young rat, potentially limiting the therapeutic potential of O-GlcNAc stimulation in young septic rats. The aim is to evaluate whether O-GlcNAc stimulation can improve sepsis outcome in young rats. Endotoxemic challenge was induced in 28-day-old rats by lipopolysaccharide injection (E. Coli O111:B4, 20 mg·kg−1) and compared to control rats (NaCl 0.9%). One hour after lipopolysaccharide injection, rats were randomly assigned to no therapy, fluidotherapy (NaCl 0.9%, 10 mL·kg−1) ± NButGT (10 mg·kg−1) to increase O-GlcNAcylation levels. Physiological parameters and plasmatic markers were evaluated 2h later. Finally, untargeted mass spectrometry was performed to map cardiac O-GlcNAcylated proteins. Lipopolysaccharide injection induced shock with a decrease in mean arterial pressure and alteration of biological parameters (p < 0.05). NButGT, contrary to fluidotherapy, was associated with an improvement of arterial pressure (p < 0.05). ATP citrate lyase was identified among the O-GlcNAcylated proteins. In conclusion, O-GlcNAc stimulation improves outcomes in young septic rats. Interestingly, identified O-GlcNAcylated proteins are mainly involved in cellular metabolism.

scholarly journals Lipogenesis from ketone bodies in rat brain. Evidence for conversion of acetoacetate into acetyl-coenzyme A in the cytosol

1976 ◽  
Vol 156 (3) ◽  
pp. 603-607 ◽  
Author(s):  
M S Patel ◽  
O E Owen
Keyword(s):  
Rat Brain ◽  
Ketone Bodies ◽  
Brain Mitochondria ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Cellular Compartment ◽  
Brain Lipids ◽  
Acetyl Coenzyme A ◽  
Citrate Lyase ◽  
Old Rats

The metabolism of acetoacetate via a proposed cytosolic pathway in brain of 1-week-old rats was investigated. (-)-Hydroxycitrate, an inhibitor of ATP citrate lyase, markedly inhibited the incorporation of carbon from labelled glucose and 3-hydroxybutyrate into cerebral lipids, but had no effect on the incorporation of labelled acetate and acetoacetate into brain lipids. Similarly, n-butylmalonate and benzene-1,2,3-tricarboxylate inhibited the incorporation of labelled 3-hydroxybutyrate but not of acetoacetate into cerebral lipids. These inhibitors had no effect on the oxidation to 14CO2 of the labelled substrates used. (-)-Hydroxycitrate decreased the incorporation of 3H from 3H2O into cerebral lipids by slices metabolizing either glucose or 3-hydroxybutyrate, but not in the presence of acetoacetate. (-)-Hydroxycitrate also differentially inhibited the incorporation of [2-14C]-leucine and [U-14C]leucine into cerebral lipids. The data show that, although the acetyl moiety of acetyl-CoA generated in brain mitochondria is largely translocated as citrate from these organelles to the cytosol, a cytosolic pathway exists by which acetoacetate is converted directly into acetyl-COA in this cellular compartment.

scholarly journals O-GlcNAc stimulation is beneficial in sepsis in the young rat, involvement of the ATP-citrate lyase

2021 ◽  
Vol 13 (2) ◽  
pp. 205
Author(s):  
T. Dupas ◽  
M. Denis ◽  
A. Persello ◽  
J. Dontaine ◽  
L. Bultot ◽  
...  
Keyword(s):  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Young Rat

Endotoxin Alteration of the Mucopolysaccharide Blood Vessel Coating in Rats

1974 ◽  
Vol 32 ◽  
pp. 148-149
Author(s):  
D. E. Philpott ◽  
A. Takahashi
Keyword(s):  
Skeletal Muscle ◽  
Endothelial Cells ◽  
Salivary Gland ◽  
Carotid Artery ◽  
Basement Membrane ◽  
Coronary Vessels ◽  
Ruthenium Red ◽  
E Coli ◽  
Old Rats ◽  
The Brain

Two month, eight month and two year old rats were treated with 10 or 20 mg/kg of E. Coli endotoxin I. P. The eight month old rats proved most resistant to the endotoxin. During fixation the aorta, carotid artery, basil arartery of the brain, coronary vessels of the heart, inner surfaces of the heart chambers, heart and skeletal muscle, lung, liver, kidney, spleen, brain, retina, trachae, intestine, salivary gland, adrenal gland and gingiva were treated with ruthenium red or alcian blue to preserve the mucopolysaccharide (MPS) coating. Five, 8 and 24 hrs of endotoxin treatment produced increasingly marked capillary damage, disappearance of the MPS coating, edema, destruction of endothelial cells and damage to the basement membrane in the liver, kidney and lung.

Cloning and Expression Analysis of ATP-Citrate Lyase Genes from Sugarcane

2013 ◽  
Vol 38 (11) ◽  
pp. 2024-2033 ◽  
Author(s):  
Chang-Ning LI ◽  
Qian NONG ◽  
Qin-Liang TAN ◽  
SRIVASTAVA Manoj Kumar ◽  
Li-Tao YANG ◽  
...  
Keyword(s):  
Expression Analysis ◽  
Cloning And Expression ◽  
Atp Citrate Lyase ◽  
Citrate Lyase

Antimicrobial Activity of Silver Nanoparticles Prepared Under an Ultrasonic Field

2011 ◽  
Vol 4 (3) ◽  
pp. 1491-1496
Author(s):  
Umadevi M ◽  
Rani T ◽  
Balakrishnan T ◽  
Ramanibai R
Keyword(s):  
Escherichia Coli ◽  
Antimicrobial Activity ◽  
Silver Nanoparticles ◽  
Reduction Method ◽  
Therapeutic Potential ◽  
Chemical Reduction ◽  
Ultrasonic Field ◽  
Great Promise ◽  
Chemical Reduction Method ◽  
E Coli

Nanotechnology has great promise for improving the therapeutic potential of medicinal molecules and related agents. In this study, silver nanoparticles of different sizes were synthesized in an ultrasonic field using the chemical reduction method with sodium borohydride as a reducing agent. The size effect of silver nanoparticles on antimicrobial activity were tested against the microorganisms Staphylococcus aureus (MTCC No. 96), Bacillus subtilis (MTCC No. 441), Streptococcus mutans (MTCC No. 497), Escherichia coli (MTCC No. 739) and Pseudomonas aeruginosa (MTCC No. 1934). The results shows that B. subtilis, and E. coli were more sensitive to silver nanoparticles and its size, indicating the superior antimicrobial efficacy of silver nanoparticles. 

PAF increases vascular permeability without increasing pulmonary arterial pressure in the rat

2001 ◽  
Vol 90 (1) ◽  
pp. 261-268 ◽  
Author(s):  
Leonardo C. Clavijo ◽  
Mary B. Carter ◽  
Paul J. Matheson ◽  
Mark A. Wilson ◽  
William B. Wead ◽  
...  
Keyword(s):  
Arterial Pressure ◽  
Pulmonary Edema ◽  
Pulmonary Arterial Pressure ◽  
Ex Vivo ◽  
Platelet Activating Factor ◽  
Microvascular Permeability ◽  
Blue Dye ◽  
E Coli ◽  
Pulmonary Arterial

In vivo pulmonary arterial catheterization was used to determine the mechanism by which platelet-activating factor (PAF) produces pulmonary edema in rats. PAF induces pulmonary edema by increasing pulmonary microvascular permeability (PMP) without changing the pulmonary pressure gradient. Rats were cannulated for measurement of pulmonary arterial pressure (Ppa) and mean arterial pressure. PMP was determined by using either in vivo fluorescent videomicroscopy or the ex vivo Evans blue dye technique. WEB 2086 was administered intravenously (IV) to antagonize specific PAF effects. Three experiments were performed: 1) IV PAF, 2) topical PAF, and 3) Escherichia coli bacteremia. IV PAF induced systemic hypotension with a decrease in Ppa. PMP increased after IV PAF in a dose-related manner. Topical PAF increased PMP but decreased Ppa only at high doses. Both PMP (88 ± 5%) and Ppa (50 ± 3%) increased during E. coli bacteremia. PAF-receptor blockade prevents changes in Ppa and PMP after both topical PAF and E. coli bacteremia. PAF, which has been shown to mediate pulmonary edema in prior studies, appears to act in the lung by primarily increasing microvascular permeability. The presence of PAF might be prerequisite for pulmonary vascular constriction during gram-negative bacteremia.

Acetyl-CoA is produced by the citrate synthase homology module of ATP-citrate lyase

2021 ◽  
Author(s):  
Kenneth Verstraete ◽  
Koen H. G. Verschueren ◽  
Ann Dansercoer ◽  
Savvas N. Savvides
Keyword(s):  
Citrate Synthase ◽  
Atp Citrate Lyase ◽  
Acetyl Coa ◽  
Citrate Lyase ◽  
Homology Module

scholarly journals IGF1-mediated HOXA13 overexpression promotes colorectal cancer metastasis through upregulating ACLY and IGF1R

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Chenyang Qiao ◽  
Wenjie Huang ◽  
Jie Chen ◽  
Weibo Feng ◽  
Tongyue Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Growth Factor ◽  
Cancer Metastasis ◽  
Combined Treatment ◽  
Insulin Like Growth Factor ◽  
Atp Citrate Lyase ◽  
Citrate Lyase ◽  
Elevated Expression ◽  
Igf1r Inhibitor ◽  
Colorectal Cancer Metastasis

AbstractMetastasis is the major reason for the high mortality of colorectal cancer (CRC) patients and its molecular mechanism remains unclear. Here, we report a novel role of Homeobox A13 (HOXA13), a member of the Homeobox (HOX) family, in promoting CRC metastasis. The elevated expression of HOXA13 was positively correlated with distant metastasis, higher AJCC stage, and poor prognosis in two independent CRC cohorts. Overexpression of HOXA13 promoted CRC metastasis whereas downregulation of HOXA13 suppressed CRC metastasis. Mechanistically, HOXA13 facilitated CRC metastasis by transactivating ATP-citrate lyase (ACLY) and insulin-like growth factor 1 receptor (IGF1R). Knockdown of ACLY and IGFIR inhibited HOXA13-medicated CRC metastasis, whereas ectopic overexpression of ACLY and IGFIR rescued the decreased CRC metastasis induced by HOXA13 knockdown. Furthermore, Insulin-like growth factor 1 (IGF1), the ligand of IGF1R, upregulated HOXA13 expression through the PI3K/AKT/HIF1α pathway. Knockdown of HOXA13 decreased IGF1-mediated CRC metastasis. In addition, the combined treatment of ACLY inhibitor ETC-1002 and IGF1R inhibitor Linsitinib dramatically suppressed HOXA13-mediated CRC metastasis. In conclusion, HOXA13 is a prognostic biomarker in CRC patients. Targeting the IGF1-HOXA13-IGF1R positive feedback loop may provide a potential therapeutic strategy for the treatment of HOXA13-driven CRC metastasis.

scholarly journals Treatment potential of LPCN 1144 on liver health and metabolic regulation in a non-genomic, high fat diet induced NASH rabbit model

2021 ◽  
Author(s):  
P. Comeglio ◽  
E. Sarchielli ◽  
S. Filippi ◽  
I. Cellai ◽  
G. Guarnieri ◽  
...  
Keyword(s):  
Hepatic Fibrosis ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Therapeutic Potential ◽  
Rabbit Model ◽  
Free Testosterone ◽  
Preclinical Model ◽  
High Fat ◽  
Liver Health ◽  
Metabolic Dysfunctions

Abstract Purpose Low free testosterone (T) level in men is independently associated with presence and severity of Non-Alcoholic Steatohepatitis (NASH). The histological and molecular effects of oral testosterone prodrug LPCN 1144 treatment on hepatic fibrosis and NASH features are unknown. A metabolic syndrome-induced NASH model in rabbits consuming high fat diet (HFD) has been previously used to assess treatment effects of injectable T on hepatic fibrosis and NASH features. Here we present results on LPCN 1144 in this HFD-induced, NASH preclinical model. Methods Male rabbits were randomly assigned to five groups: regular diet (RD), HFD, HFD + 1144 vehicle (HFD + Veh), HFD + 1144 (1144), and HFD + 1144 + α-tocopherol (1144 + ALPHA). Rabbits were sacrificed after 12 weeks for liver histological, biochemical and genetic analyses. Histological scores were obtained through Giemsa (inflammation), Masson’s trichrome (steatosis and ballooning), and Picrosirius Red (fibrosis) staining. Results Compared to RD, HFD and HFD + Veh significantly worsened NASH features and hepatic fibrosis. Considering HFD and HFD + Veh arms, histological and biomarker features were not significantly different. Both 1144 and 1144 + ALPHA arms improved mean histological scores of NASH as compared to HFD arm. Importantly, percentage of fibrosis was improved in both 1144 (p < 0.05) and 1144 + ALPHA (p = 0.05) treatment arms vs. HFD. Both treatment arms also reduced HFD-induced inflammation and fibrosis mRNA markers. Furthermore, 1144 treatments significantly improved HFD-induced metabolic dysfunctions. Conclusions Histological and biomarker analyses demonstrate that LPCN 1144 improved HFD-induced hepatic fibrosis and NASH biochemical, biomolecular and histochemical features. These preclinical findings support a therapeutic potential of LPCN 1144 in the treatment of NASH and of hepatic fibrosis.

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