scholarly journals Global Lysine Acetylome Analysis of LPS-Stimulated HepG2 Cells Identified Hyperacetylation of PKM2 as a Metabolic Regulator in Sepsis

2021 ◽  
Vol 22 (16) ◽  
pp. 8529
Author(s):  
Ann-Yae Na ◽  
Sanjita Paudel ◽  
Soyoung Choi ◽  
Jun Hyung Lee ◽  
Min-Sik Kim ◽  
...  
Keyword(s):  
Liver Dysfunction ◽  
Lactate Level ◽  
Hepg2 Cells ◽  
Lactate Concentration ◽  
Lysine Acetylation ◽  
Post Translational Modification ◽  
Glycolysis Pathway ◽  
The Relationship ◽  
Causative Link ◽  
Lps Treatment

Sepsis-induced liver dysfunction (SILD) is a common event and is strongly associated with mortality. Establishing a causative link between protein post-translational modification and diseases is challenging. We studied the relationship among lysine acetylation (Kac), sirtuin (SIRTs), and the factors involved in SILD, which was induced in LPS-stimulated HepG2 cells. Protein hyperacetylation was observed according to SIRTs reduction after LPS treatment for 24 h. We identified 1449 Kac sites based on comparative acetylome analysis and quantified 1086 Kac sites on 410 proteins for acetylation. Interestingly, the upregulated Kac proteins are enriched in glycolysis/gluconeogenesis pathways in the Kyoto Encyclopedia of Genes and Genomes (KEGG) category. Among the proteins in the glycolysis pathway, hyperacetylation, a key regulator of lactate level in sepsis, was observed at three pyruvate kinase M2 (PKM2) sites. Hyperacetylation of PKM2 induced an increase in its activity, consequently increasing the lactate concentration. In conclusion, this study is the first to conduct global profiling of Kac, suggesting that the Kac mechanism of PKM2 in glycolysis is associated with sepsis. Moreover, it helps to further understand the systematic information regarding hyperacetylation during the sepsis process.

scholarly journals Alterations in cellular and organellar phospholipid compositions of HepG2 cells during cell growth

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Tokuji Tsuji ◽  
Shin-ya Morita ◽  
Yoshinobu Nakamura ◽  
Yoshito Ikeda ◽  
Taiho Kambe ◽  
...  
Keyword(s):  
Cell Growth ◽  
Hepg2 Cells ◽  
Phospholipid Class ◽  
Present Report ◽  
Phospholipid Metabolism ◽  
Cancer Cell Growth ◽  
Microsomal Membranes ◽  
Intracellular Organelles ◽  
The Relationship ◽  
Pe Ratio

AbstractThe human hepatoblastoma cell line, HepG2, has been used for investigating a wide variety of physiological and pathophysiological processes. However, less information is available about the phospholipid metabolism in HepG2 cells. In the present report, to clarify the relationship between cell growth and phospholipid metabolism in HepG2 cells, we examined the phospholipid class compositions of the cells and their intracellular organelles by using enzymatic fluorometric methods. In HepG2 cells, the ratios of all phospholipid classes, but not the ratio of cholesterol, markedly changed with cell growth. Of note, depending on cell growth, the phosphatidic acid (PA) ratio increased and phosphatidylcholine (PC) ratio decreased in the nuclear membranes, the sphingomyelin (SM) ratio increased in the microsomal membranes, and the phosphatidylethanolamine (PE) ratio increased and the phosphatidylserine (PS) ratio decreased in the mitochondrial membranes. Moreover, the mRNA expression levels of enzymes related to PC, PE, PS, PA, SM and cardiolipin syntheses changed during cell growth. We suggest that the phospholipid class compositions of organellar membranes are tightly regulated by cell growth. These findings provide a basis for future investigations of cancer cell growth and lipid metabolism.

scholarly journals Lipopolysaccharides promote pulmonary fibrosis in silicosis through the aggravation of apoptosis and inflammation in alveolar macrophages

2020 ◽  
Vol 15 (1) ◽  
pp. 598-605
Author(s):  
Shiyi Tan ◽  
Shang Yang ◽  
Mingke Chen ◽  
Yurun Wang ◽  
Li Zhu ◽  
...  
Keyword(s):  
Pulmonary Fibrosis ◽  
Alveolar Macrophages ◽  
Inflammatory Factors ◽  
Necrosis Factor Alpha ◽  
Defensive Role ◽  
Factor Alpha ◽  
Apoptosis And Inflammation ◽  
The Relationship ◽  
Lps Treatment ◽  
Necrosis Factor

AbstractAlveolar macrophages (AMs) play an important defensive role by removing dust and bacteria from alveoli. Apoptosis of AMs is associated with lung fibrosis; however, the relationship between this apoptotic event and environmental factors, such as the presence of lipopolysaccharides (LPSs) in the workplace, has not yet been addressed. To investigate whether exposure to LPS can exacerbate fibrosis, we collected AMs from 12 male workers exposed to silica and incubated them in the presence and absence of LPS for 24 h. We show that the levels of cleaved caspase-3 and pro-inflammatory cytokines interleukin (IL)-1β, IL-6, and tumor necrosis factor-alpha were increased in these AMs following LPS treatment. Moreover, we demonstrate that LPS exposure aggravated apoptosis and the release of inflammatory factors in AMs in a mouse model of silicosis, which eventually promoted pulmonary fibrosis. These results suggest that exposure to LPS may accelerate the progression of pulmonary fibrosis in silicosis by increasing apoptosis and inflammation in AMs.

MAPK p38/Ulk1 pathway inhibits autophagy and induces IL-1β expression in hepatic stellate cells

2022 ◽  
Author(s):  
Li Jin ◽  
Juan Li ◽  
ShuJuan Yang ◽  
Rou Zhang ◽  
Chunhua Hu ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Hepatic Inflammation ◽  
The Past ◽  
Cytokine Induction ◽  
Cytokines And Chemokines ◽  
The Relationship ◽  
Autophagy Inhibition ◽  
Lps Treatment

Background: In the past, hepatic stellate cells (HSCs) were considered to be noninflammatory cells and contribute to liver fibrosis by producing extracellular matrix. Recently, it was found that HSCs can also secrete cytokines and chemokines and therefore participate in hepatic inflammation. Autophagy participates in many immune response processes in immune cells. It is unclear whether autophagy is involved in inflammatory cytokine induction in HSCs. Methods: MAPK p38, Ulk1 phosphorylation and the Ulk1-Atg13 complex were analyzed in HSC-T6 cells after LPS treatment. The relationship between autophagy inhibition and inflammation was investigated in primary rat HSCs. Results: We discovered that LPS inhibited autophagy through MAPK p38. The activation of MAPK p38 induced Ulk1 phosphorylation, which disrupted the Ulk1-Atg13 complex and therefore inhibited autophagy. Furthermore, in primary rat HSCs, we demonstrated that autophagy inhibition regulated IL-1β induction, which depended on the MAPK p38/Ulk1 pathway. Conclusions: Our results reveal a continuous signaling pathway, MAPK p38-Ulk1 phosphorylation-Ulk1/Atg13 disruption, which inhibits autophagy and induces IL-1β expression in HSCs.

Agreement between i-STAT and YSI 2300 devices to determine lactate concentrations in dogs undergoing exercise

2016 ◽  
Vol 12 (2) ◽  
pp. 75-82 ◽  
Author(s):  
C. Berkman ◽  
M.C. Pereira ◽  
K.B. Nardi ◽  
G.T. Pereira ◽  
O.A.B. Soares ◽  
...  
Keyword(s):  
Venous Blood ◽  
Lactate Concentration ◽  
Intense Exercise ◽  
Blood Samples ◽  
Handheld Device ◽  
Clinical Evaluations ◽  
Small Constant ◽  
Constant Bias ◽  
Highly Correlated ◽  
The Relationship

Little information is available comparing the i-STAT and the YSI 2300 Stat Plus devices to determine the lactate concentration [Lac] in dogs undergoing intense exercise. The reproducibility of the YSI 2300 for quantifying the [Lac] in canine blood [Lac]b and plasma [Lac]p samples has been observed. In addition, the i-STAT handheld device was used to quantify [Lac] in dogs subjected to exercise, and the results were compared with that of YSI 2300. Venous blood samples of Beagle and American Pit Bull Terrier dogs were obtained during an intense exercise training on a treadmill. [Lac]p and [Lac]b were quantified using the YSI 2300 instrument to determine the reproducibility of the results. A total of 52 specimens were compared for both plasma and whole blood. For comparing the devices (YSI 2300 vs i-STAT), 96 samples were used. Ordinary least products regression, the correlation coefficient, and Bland-Altman plots were used to assess the agreement of using the i-STAT device. The relationship between duplicate measurements of both [Lac]b and [Lac]p by YSI 2300 was strong (r=0.99). A correlation between the data obtained using the i-STAT and YSI 2300 instruments was observed for both the [Lac]p (r=0.97) and [Lac]b (r=0.88). The i-STAT exhibited a small constant bias (-0.25 mmol/l) compared to YSI 2300 ([Lac]b). There were proportional biases of 0.89 mmol/l for [Lac]p and 1.22 mmol/l for [Lac]b when using YSI 2300 vs i-STAT. We confirmed the reproducibility of the YSI 2300 for canine lactate blood/plasma samples. The results obtained by the i-STAT and YSI 2300 analyser were highly correlated, but a small constant bias was observed between them. The i-STAT device can be used in clinical evaluations, and it is also adequate for designing and monitoring fitness programmes.

scholarly journals Effects of the regional nerve blockade at the limb reperfusion in pediatric orthopedics

2020 ◽  
Vol 24 (5) ◽  
pp. 317-322
Author(s):  
Olga G. Chekhova ◽  
V. A. Ostanina ◽  
A. H. Shmakov
Keyword(s):  
Regional Anesthesia ◽  
Lactate Level ◽  
Lactate Concentration ◽  
Main Stage ◽  
Topical Anesthetic ◽  
Nerve Blockade ◽  
Arterial Blood ◽  
Group I ◽  
Group Ii ◽  
Arterial Blood Glucose

Introduction. Arterial tourniquets are widely used to improve visualization of the surgical field and to reduce blood loss . However, the resulting ischemia and subsequent reperfusion make doctors seek for better options to reduce these complications. Objective. To find out how the regional nerve blockade impacts the reperfusion of ischemized limb when arterial tourniquets are removed during orthopedic surgeries in children. Material and methods. In 16 patients, who were operated on at the department of trauma and orthopedics of the Novosibirsk Children ‘s Clinical Hospital of Emergency Medical Care (CCHEMC) , surgical intervention required the application of an arterial tourniquet. These patients became participants in an observational pilot study. Patients with tourniquets were divided into two groups: Group I - had the regional nerve blockade ( 9 patients) and Group II - had no regional nerve blockade (7 patients). Parameters of acid-base homeostasis, lactate and arterial blood glucose were assessed in all patients at all stages: before surgery (stage 1), main stage (stage 2), 5 minutes after the tourniquet removal (stage 3). The following parameters were compared in this work: mean arterial pressure (MAP), mm Hg; heart rate (min-1); concentration of lactate in the arterial blood (mmol/l), glycemia (mmol/l). The obtained findings are presented as median (Me) of lower and upper quartiles [Q25; Q75]. Results. The found dynamics of lactate concentration in participants’ blood was the most significant result of the study. In Group I, where regional anesthesia was used, lactate level decreased at the stage 2 and returned to its baseline at the stage 3. In Group II (without regional anesthesia, but with a powerful central analgesic preparation) , lactate level did not change at stage 2, but significantly increased at stage 3. Conclusion. Topical anesthetic (Ropivakaine), used in the regional nerve blockade during orthopedic surgeries in children when arterial tourniquets are put, has less harmful effects in surgical aggression.

scholarly journals The Regulation of Haemocyanin Oxygen Affinity During Emersion of the Crayfish Austropotamobius Pallipes: III. The Dependence of Ca2+-Haemocyanin Binding on the Concentration Of L-Lactate

1987 ◽  
Vol 133 (1) ◽  
pp. 339-352
Author(s):  
S. MORRIS ◽  
C.R. BRIDGES ◽  
M. K. GRIESHABER
Keyword(s):  
Biological Sciences ◽  
Binding Sites ◽  
Lactate Concentration ◽  
Oxygen Affinity ◽  
Calcium Lactate ◽  
Worst Case ◽  
Austropotamobius Pallipes ◽  
University Of Calgary ◽  
Lactate Formation ◽  
The Relationship

The binding of Ca2+ to the haemocyanin of the crayfish Austropotamobius pallipes was investigated. The amount of bound Ca2+ was determined using an ultrafiltration technique to produce haemocyanin-free solutions, the Ca2+ concentration of which could then be compared with that of the original, unfiltered solution. Any difference between the two values would indicate the amount of calcium bound by haemocyanin. The effect of L-lactate on Ca2+ binding was investigated by determining the amount of bound ion at different concentrations of L-lactate. In addition, oxygen equilibrium curves were constructed for some of the solutions to verify that the haemocyanin oxygen affinity remained sensitive to L-lactate and to determine whether the haemocyanin was functionally similar to that used in previous investigations. With 17 mmol 1−1 total Ca2+ and approximately 1 mmol 1−1 L-lactate the number of Ca2+ binding sites was estimated to be between eight and nine per haemocyanin molecule. Without taking into account the formation of calcium lactate, the observed dependency of Ca2+-haemocyanin binding on L-lactate concentration could best be described by the equation: Ca2+/Hc = 8.64-0.32[lactate−]. A ‘worst case’ estimate for maximum calcium lactate formation, assuming Ca2+ to be the only counterion available to lactate, altered the relationship slightly to: Ca2+/Hc = 8.65-0.35[lactate−]. Note: Present address: Department of Biological Sciences, University of Calgary, 2500 University Drive N/V, Calgary, Alberta, Canada T2N 1N4.

scholarly journals Comment on ‘YcgC represents a new protein deacetylase family in prokaryotes’

eLife ◽  
2018 ◽  
Vol 7 ◽  
Author(s):  
Magdalena Kremer ◽  
Nora Kuhlmann ◽  
Marius Lechner ◽  
Linda Baldus ◽  
Michael Lammers
Keyword(s):  
Lysine Acetylation ◽  
Post Translational Modification ◽  
Donor Molecule ◽  
Acetyl Coa ◽  
Lysine Deacetylases ◽  
Protein Deacetylase ◽  
New Protein

Lysine acetylation is a post-translational modification that is conserved from bacteria to humans. It is catalysed by the activities of lysine acetyltransferases, which use acetyl-CoA as the acetyl-donor molecule, and lysine deacetylases, which remove the acetyl moiety. Recently, it was reported that YcgC represents a new prokaryotic deacetylase family with no apparent homologies to existing deacetylases (Tu et al., 2015). Here we report the results of experiments which demonstrate that YcgC is not a deacetylase.

scholarly journals A Case of Montelukast-Induced Churg-Strauss Syndrome Associated with Liver Dysfunction

2011 ◽  
Vol 2011 ◽  
pp. 1-4
Author(s):  
Keiji Matsui ◽  
Kosuke Nishijima
Keyword(s):  
Liver Dysfunction ◽  
Carnitine Deficiency ◽  
Acid Oxidation ◽  
Fatty Change ◽  
Churg Strauss Syndrome ◽  
History Of ◽  
Strauss Syndrome ◽  
Leukotriene Receptor ◽  
The Relationship ◽  
Churg Strauss

A 64-year-old woman was admitted to hospital due to protracted diarrhea and liver dysfunction. The patient was diagnosed as Churg-Strauss syndrome (CSS) due to asthma, paranasal sinusitis, hypereosinophilia, and polyneuropathy. There was a history of taking montelukast, a leukotriene receptor antagonist (LTRA), which is thought to have some relationship with CSS. The liver biopsy specimen showed eosinophilic infiltration and centrolobular fatty change. In this paper, we review the relationship between LTRA and CSS. Several lines of evidence suggest that leukotriene plays an important role in maintaining neural tissues. We also review the potential relationship between centrolobular fatty change and pivoxil-containing antibiotics, which was prescribed for sinusitis before admission. Carnitine deficiency induced by pivoxil-containing agents may cause impaired fatty acid oxidation in mitochondria.

Blood Lactate Concentration and Clearance in Elite Swimmers During Competition

2011 ◽  
Vol 6 (1) ◽  
pp. 106-117 ◽  
Author(s):  
Jason D. Vescovi ◽  
Olesya Falenchuk ◽  
Greg D. Wells
Keyword(s):  
Blood Lactate ◽  
Lactate Concentration ◽  
Blood Lactate Concentration ◽  
Active Recovery ◽  
Competitive Swimming ◽  
Elite Swimmers ◽  
Lactate Removal ◽  
The Relationship ◽  
Competitive Swimmers ◽  
Effect Of Age

Purpose:Blood lactate concentration, [BLa], after swimming events might be influenced by demographic features and characteristics of the swim race, whereas active recovery enhances blood lactate removal. Our aims were to (1) examine how sex, age, race distance, and swim stroke influenced [BLa] after competitive swimming events and (2) develop a practical model based on recovery swim distance to optimize blood lactate removal.Methods:We retrospectively analyzed postrace [BLa] from 100 swimmers who competed in the finals at the Canadian Swim Championships. [BLa] was also assessed repeatedly during the active recovery. Generalized estimating equations were used to evaluate the relationship between postrace [BLa] with independent variables.Results:Postrace [BLa] was highest following 100–200 m events and lowest after 50 and 1500 m races. A sex effect for postrace [BLa] was observed only for freestyle events. There was a negligible effect of age on postrace [BLa]. A model was developed to estimate an expected change in [BLa] during active recovery (male = 0; female = 1): [BLa] change after active recovery = –3.374 + (1.162 × sex) + (0.789 × postrace [BLa]) + (0.003 × active recovery distance).Conclusions:These findings indicate that swimmers competing at an elite standard display similar postrace [BLa] and that there is little effect of age on postrace [BLa] in competitive swimmers aged 14 to 29 y.

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