scholarly journals Vitamin K Vitamers Differently Affect Energy Metabolism in IPEC-J2 Cells

2021 ◽  
Vol 8 ◽  
Author(s):  
Chiara Bernardini ◽  
Cristina Algieri ◽  
Debora La Mantia ◽  
Fabiana Trombetti ◽  
Alessandra Pagliarani ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Vitamin K ◽  
De Novo ◽  
Functional Model ◽  
Hydrocarbon Chain ◽  
Structural Features ◽  
Nitrogen Recycling ◽  
Matrix Space ◽  
Atp Production

The fat-soluble vitamin K (VK) has long been known as a requirement for blood coagulation, but like other vitamins, has been recently recognized to play further physiological roles, particularly in cell development and homeostasis. Vertebrates cannot de novo synthesize VK, which is essential, and it can only be obtained from the diet or by the activity of the gut microbiota. The IPEC-J2 cell line, obtained from porcine small intestine, which shows strong similarities to the human one, represents an excellent functional model to in vitro study the effect of compounds at the intestinal level. The acute VK treatments on the bioenergetic features of IPEC-J2 cells were evaluated by Seahorse XP Agilent technology. VK exists in different structurally related forms (vitamers), all featured by a naphtoquinone moiety, but with distinct effects on IPEC-J2 energy metabolism. The VK1, which has a long hydrocarbon chain, at both concentrations (5 and 10 μM), increases the cellular ATP production due to oxidative phosphorylation (OXPHOS) by 5% and by 30% through glycolysis. The VK2 at 5 μM only stimulates ATP production by OXPHOS. Conversely, 10 μM VK3, which lacks the long side chain, inhibits OXPHOS by 30% and glycolysis by 45%. However, even if IPEC-J2 cells mainly prefer OXPHOS to glycolysis to produce ATP, the OXPHOS/glycolysis ratio significantly decreases in VK1-treated cells, is unaffected by VK2, and only significantly increased by 10 μM VK3. VK1, at the two concentrations tested, does not affect the mitochondrial bioenergetic parameters, while 5 μM VK2 increases and 5 μM VK3 reduces the mitochondrial respiration (i.e., maximal respiration and spare respiratory capacity). Moreover, 10 μM VK3 impairs OXPHOS, as shown by the increase in the proton leak, namely the proton backward entry to the matrix space, thus pointing out mitochondrial toxicity. Furthermore, in the presence of both VK1 and VK2 concentrations, the glycolytic parameters, namely the glycolytic capacity and the glycolytic reserve, are unaltered. In contrast, the inhibition of glycoATP production by VK3 is linked to the 80% inhibition of glycolysis, resulting in a reduced glycolytic capacity and reserve. These data, which demonstrate the VK ability to differently modulate IPEC-J2 cell energy metabolism according to the different structural features of the vitamers, can mirror VK modulatory effects on the cell membrane features and, as a cascade, on the epithelial cell properties and gut functions: balance of salt and water, macromolecule cleavage, detoxification of harmful compounds, and nitrogen recycling.

Liquid Chromatographic Determination of Sphmgamne and Sphingosine: Use of the Free Sphinganine-to-Sphingosine Ratio as a Biomarker for Consumption of Fumonisins

1994 ◽  
Vol 77 (2) ◽  
pp. 533-540 ◽  
Author(s):  
Ronald T Riley ◽  
Elaine Wang ◽  
Alfred H Merrill
Keyword(s):  
De Novo ◽  
Fumonisin B1 ◽  
Chromatographic Determination ◽  
Structural Features ◽  
Serum Marker ◽  
Fungal Culture ◽  
Sphingoid Bases ◽  
Study Results ◽  
Liquid Chromatographic

Abstract Because the chemical structure of fumonisin B1 (FB1) has several structural features in common with the sphingoid bases, sphingosine and dihydro-sphingosine (sphinganine), we tested the hypothesis that the fumonisins might alter the normal cellular activity or the metabolism of endogenous free sphingoid bases. FB1 was found to be a potent inhibitor of de novo sphingolipid biosynthesis in vitro, its primary target being sphinganine N-acyl-transferase. This inhibition resulted in a decrease in the biosynthesis of sphingosine and an accumulation of free sphinganine, an intermediate in the de novo biosynthetic pathway for complex sphin-golipids. These findings led to the hypothesis that consumption of feed containing fumo|nisins should cause an increase in the ratio of free sphinganine to free sphingosine in tissues and serum. Data consistent with this hypothesis have been obtained from horses and pigs that consumed feed containing fumonisin-contaminated corn screenings and from rats fed feed supplemented with fumonisin-containing fungal culture materials or pure FBi. Thus, the ratio of free sphinganine to free sphingosine shows promise as a tissue, urine, or serum marker for animals consuming feed containing fumonisins. The present paper provides a detailed description of the extraction of free sphingoid bases and the liquid chromatographic method we used for determining the relative amounts of free sphingosine and free sphinganine in serum, urine, and various tissues of animals. Study results are summarized, and the ratio of free sphinganine to free sphingosine is discussed as a presumptive test for identifying animals consuming fumonisin-contami-nated feed.

scholarly journals SLC25A1 promotes tumor growth and survival by reprogramming energy metabolism in colorectal cancer

2021 ◽  
Vol 12 (12) ◽  
Author(s):  
Ying Yang ◽  
Jiaxing He ◽  
Bo Zhang ◽  
Zhansheng Zhang ◽  
Guozhan Jia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Lipid Metabolism ◽  
Energy Metabolism ◽  
Cell Apoptosis ◽  
De Novo ◽  
Lipid Synthesis ◽  
Growth And Survival ◽  
Metabolism Regulation

AbstractAbnormal lipid metabolism has been commonly observed in various human cancers, including colorectal cancer (CRC). The mitochondrial citrate carrier SLC25A1 (also known as mitochondrial citrate/isocitrate carrier, CIC), has been shown to play an important role in lipid metabolism regulation. Our bioinformatics analysis indicated that SLC25A1 was markedly upregulated in CRC. However, the role of SLC25A1 in the pathogenesis and aberrant lipid metabolism in CRC remain unexplored. Here, we found that SLC25A1 expression was significantly increased in tumor samples of CRC as compared with paired normal samples, which is associated with poor survival in patients with CRC. Knockdown of SLC25A1 significantly inhibited the growth of CRC cells by suppressing the progression of the G1/S cell cycle and inducing cell apoptosis both in vitro and in vivo, whereas SLC25A1 overexpression suppressed the malignant phenotype. Additionally, we demonstrated that SLC25A1 reprogrammed energy metabolism to promote CRC progression through two mechanisms. Under normal conditions, SLC25A1 increased de novo lipid synthesis to promote CRC growth. During metabolic stress, SLC25A1 increased oxidative phosphorylation (OXPHOS) to protect protects CRC cells from energy stress-induced cell apoptosis. Collectively, SLC25A1 plays a pivotal role in the promotion of CRC growth and survival by reprogramming energy metabolism. It could be exploited as a novel diagnostic marker and therapeutic target in CRC.

scholarly journals Quantitative Structure–Activity Relationship Evaluation of MDA-MB-231 Cell Anti-Proliferative Leads

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4795
Author(s):  
Ajaykumar Gandhi ◽  
Vijay Masand ◽  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Anis Ben Ghorbal ◽  
...  
Keyword(s):  
De Novo ◽  
Quantitative Structure Activity Relationship ◽  
Structural Features ◽  
Quantitative Structure ◽  
Statistical Parameters ◽  
Structure Activity ◽  
Tnbc Cell ◽  
Qsar Models ◽  
Anti Tumor Activity

In the present endeavor, for the dataset of 219 in vitro MDA-MB-231 TNBC cell antagonists, a (QSAR) quantitative structure–activity relationships model has been carried out. The quantitative and explicative assessments were performed to identify inconspicuous yet pre-eminent structural features that govern the anti-tumor activity of these compounds. GA-MLR (genetic algorithm multi-linear regression) methodology was employed to build statistically robust and highly predictive multiple QSAR models, abiding by the OECD guidelines. Thoroughly validated QSAR models attained values for various statistical parameters well above the threshold values (i.e., R2 = 0.79, Q2LOO = 0.77, Q2LMO = 0.76–0.77, Q2-Fn = 0.72–0.76). Both de novo QSAR models have a sound balance of descriptive and statistical approaches. Decidedly, these QSAR models are serviceable in the development of MDA-MB-231 TNBC cell antagonists.

scholarly journals Ca2+-Dependent Interaction of S100A1 with F1-ATPase Leads to an Increased ATP Content in Cardiomyocytes

2007 ◽  
Vol 27 (12) ◽  
pp. 4365-4373 ◽  
Author(s):  
Melanie Boerries ◽  
Patrick Most ◽  
Jonathan R. Gledhill ◽  
John E. Walker ◽  
Hugo A. Katus ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
Atpase Activity ◽  
Cardiac Contractility ◽  
Gel Filtration ◽  
Dependent Manner ◽  
Atp Content ◽  
Atp Production ◽  
Rat Hearts

ABSTRACT S100A1, a Ca2+-sensing protein of the EF-hand family that is expressed predominantly in cardiac muscle, plays a pivotal role in cardiac contractility in vitro and in vivo. It has recently been demonstrated that by restoring Ca2+ homeostasis, S100A1 was able to rescue contractile dysfunction in failing rat hearts. Myocardial contractility is regulated not only by Ca2+ homeostasis but also by energy metabolism, in particular the production of ATP. Here, we report a novel interaction of S100A1 with mitochondrial F1-ATPase, which affects F1-ATPase activity and cellular ATP production. In particular, cardiomyocytes that overexpress S100A1 exhibited a higher ATP content than control cells, whereas knockdown of S100A1 expression decreased ATP levels. In pull-down experiments, we identified the α- and β-chain of F1-ATPase to interact with S100A1 in a Ca2+-dependent manner. The interaction was confirmed by colocalization studies of S100A1 and F1-ATPase and the analysis of the S100A1-F1-ATPase complex by gel filtration chromatography. The functional impact of this association is highlighted by an S100A1-mediated increase of F1-ATPase activity. Consistently, ATP synthase activity is reduced in cardiomyocytes from S100A1 knockout mice. Our data indicate that S100A1 might play a key role in cardiac energy metabolism.

scholarly journals A new model isolates glioblastoma clonal interactions and reveals unexpected modes for regulating motility, proliferation, and drug resistance

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Justin B Davis ◽  
Sreshta S Krishna ◽  
Ryan Abi Jomaa ◽  
Cindy T. Duong ◽  
Virginia Espina ◽  
...  
Keyword(s):  
Drug Resistance ◽  
De Novo ◽  
Functional Model ◽  
3D Culture ◽  
Interaction Network ◽  
Treatment Resistance ◽  
Cell Contact ◽  
Clonal Heterogeneity ◽  
Single Clone

AbstractTumor clonal heterogeneity drives treatment resistance. But robust models are lacking that permit eavesdropping on the basic interaction network of tumor clones. We developed an in vitro, functional model of clonal cooperation using U87MG glioblastoma cells, which isolates fundamental clonal interactions. In this model pre-labeled clones are co-cultured to track changes in their individual motility, growth, and drug resistance behavior while mixed. This highly reproducible system allowed us to address a new class of fundamental questions about clonal interactions. We demonstrate that (i) a single clone can switch off the motility of the entire multiclonal U87MG cell line in 3D culture, (ii) maintenance of clonal heterogeneity is an intrinsic and influential cancer cell property, where clones coordinate growth rates to protect slow growing clones, and (iii) two drug sensitive clones can develop resistance de novo when cooperating. Furthermore, clonal communication for these specific types of interaction did not require diffusible factors, but appears to depend on cell-cell contact. This model constitutes a straightforward but highly reliable tool for isolating the complex clonal interactions that make up the fundamental “hive mind” of the tumor. It uniquely exposes clonal interactions for future pharmacological and biochemical studies.

scholarly journals Creatine Metabolism in Female Reproduction, Pregnancy and Newborn Health

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 490 ◽  
Author(s):  
Anna Maria Muccini ◽  
Nhi T. Tran ◽  
Deborah L. de Guingand ◽  
Mamatha Philip ◽  
Paul A. Della Gatta ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
De Novo ◽  
Creatine Supplementation ◽  
Perinatal Outcomes ◽  
Small Animal ◽  
Newborn Health ◽  
Female Reproduction ◽  
Atp Production ◽  
Creatine Metabolism

Creatine metabolism is an important component of cellular energy homeostasis. Via the creatine kinase circuit, creatine derived from our diet or synthesized endogenously provides spatial and temporal maintenance of intracellular adenosine triphosphate (ATP) production; this is particularly important for cells with high or fluctuating energy demands. The use of this circuit by tissues within the female reproductive system, as well as the placenta and the developing fetus during pregnancy is apparent throughout the literature, with some studies linking perturbations in creatine metabolism to reduced fertility and poor pregnancy outcomes. Maternal dietary creatine supplementation during pregnancy as a safeguard against hypoxia-induced perinatal injury, particularly that of the brain, has also been widely studied in pre-clinical in vitro and small animal models. However, there is still no consensus on whether creatine is essential for successful reproduction. This review consolidates the available literature on creatine metabolism in female reproduction, pregnancy and the early neonatal period. Creatine metabolism is discussed in relation to cellular bioenergetics and de novo synthesis, as well as the potential to use dietary creatine in a reproductive setting. We highlight the apparent knowledge gaps and the research “road forward” to understand, and then utilize, creatine to improve reproductive health and perinatal outcomes.

Role of calcium in metabolic signaling between cardiac sarcoplasmic reticulum and mitochondria in vitro

2003 ◽  
Vol 284 (2) ◽  
pp. C285-C293 ◽  
Author(s):  
Robert S. Balaban ◽  
Salil Bose ◽  
Stephanie A. French ◽  
Paul R. Territo
Keyword(s):  
Energy Metabolism ◽  
Sarcoplasmic Reticulum ◽  
Atp Synthesis ◽  
Cardiac Sarcoplasmic Reticulum ◽  
Atp Production ◽  
Wide Range ◽  
Reconstituted System

The role of Ca2+ as a cytosolic signaling molecule between porcine cardiac sarcoplasmic reticulum (SR) ATPase and mitochondrial ATP production was evaluated in vitro. The Ca2+ sensitivity of these processes was determined individually and in a reconstituted system with SR and mitochondria in a 0.5:1 protein-to-cytochrome aa 3 ratio. The half-maximal concentration ( K 1/2) of SR ATPase was 335 nM Ca2+. The ATP synthesis dependence was similar with a K 1/2 of 243 nM for dehydrogenases and 114 nM for overall ATP production. In the reconstituted system, Ca2+ increased thapsigargin-sensitive ATP production (maximum ∼5-fold) with minimal changes in mitochondrial reduced nicotinamide adenine dinucleotide (NADH). NADH concentration remained stable despite graded increases in NADH turnover induced over a wide range of Ca2+ concentrations (0 to ∼500 nM). These data are consistent with a balanced activation of SR ATPase and mitochondrial ATP synthesis by Ca2+ that contributes to a homeostasis of energy metabolism metabolites. It is suggested that this balanced activation by cytosolic Ca2+ is partially responsible for the minimal alteration in energy metabolism intermediates that occurs with changes in cardiac workload in vivo.

scholarly journals Formate induces a metabolic switch in nucleotide and energy metabolism

2019 ◽  
Author(s):  
Kristell Oizel ◽  
Jacqueline Tait-Mulder ◽  
Jorge Fernandez-de-Cossio-Diaz ◽  
Matthias Pietzke ◽  
Holly Brunton ◽  
...  
Keyword(s):  
Energy Metabolism ◽  
De Novo ◽  
Adenine Nucleotide ◽  
Adenine Nucleotides ◽  
Theoretical Modelling ◽  
Carbamoyl Phosphate ◽  
Metabolic Switch ◽  
Ampk Activity

Formate is a precursor for the de novo synthesis of purine and deoxythymidine nucleotides. Formate also interacts with energy metabolism by promoting the synthesis of adenine nucleotides. Here we use theoretical modelling together with metabolomics analysis to investigate the link between formate, nucleotide and energy metabolism. We uncover that endogenous or exogenous formate induces a metabolic switch from low to high adenine nucleotide levels, increasing the rate of glycolysis and repressing the AMPK activity. Formate also induces an increase in the pyrimidine precursor orotate and the urea cycle intermediate argininosuccinate, in agreement with the ATP dependent activities of carbamoyl-phosphate and argininosuccinate synthetase. In vivo data for mouse and human cancers confirms the association between increased formate production, nucleotide and energy metabolism. Finally, the in vitro observations are recapitulated in mice following intraperitoneal injection of formate. We conclude that formate is a potent regulator of purine, pyrimidine and energy metabolism.

In vitro effects of various metabolic inhibitors on the formation of inactive renin and the loss of renin in rabbit uterine tissue

1981 ◽  
Vol 96 (2) ◽  
pp. 281-288 ◽  
Author(s):  
Jørgen Jørgensen
Keyword(s):  
Energy Metabolism ◽  
De Novo ◽  
Post Partum ◽  
Metabolic Inhibitors ◽  
Kidney Cortex ◽  
Uterine Tissue ◽  
Tissue Slices ◽  
Inactive Renin ◽  
A Minor

Abstract. A pronounced formation of renin occurs during incubation of non-pregnant uterine tissue slices in vitro. The synthesized renin appears in an enzymatically inactive form, which can be activated by acidification. Prior to incubation only a small fraction of inactive renin is present. The formation of inactive renin is blocked by puromycin and by inhibition of energy metabolism, indicating a de novo synthesis. A similar pattern of inhibition prevails the modest formation of inactive renin in post-partum uterus. The marked loss of active renin seen during incubation of post-partum uterine tissue is partly prevented by an inhibition of energy metabolism. Potent inhibitors are iodoacetate and chloroquine. These findings are in accordance with lysosomal engagement in the inactivation of renin. Incubated kidney cortex tissue shows only a minor loss of renin during incubation. This loss is uninfluenced by attempts to block it.

Energy Production and Utilization by Human Platelets in the Presence of Some Guanidines and Phenols (Uremic Toxins) that Inhibit Aggregation

1975 ◽  
Vol 34 (01) ◽  
pp. 063-071 ◽  
Author(s):  
Hugh J Carroll
Keyword(s):  
Platelet Aggregation ◽  
Energy Metabolism ◽  
Human Platelets ◽  
Uremic Toxins ◽  
Anaerobic Glycolysis ◽  
Excessive Bleeding ◽  
Atp Production ◽  
Uremic Patients ◽  
Induced Aggregation

SummaryPlatelet aggregation induced by ADP can be inhibited by plasma from uremic patients or by toxins isolated from their plasma, e. g. guanidinosuccinic acid, methylguanidine, phenol and hydroxyphenylacetic acids. Since these chemical substances can interfere with energy metabolism in tissues other than platelets and since ATP production is needed for ADP-induced aggregation, alterations in platelet energy metabolism could underlie excessive bleeding in uremic patients. Platelets incubated with idioacetate and deprived of anaerobic glycolysis produced the same quantity of ATP through respiration in the presence of all the uremic toxins studied as in their absence. Similarly, platelets incubated with cyanide and deprived of the oxidative pathway utilized anaerobic glycolysis to produce normal quantities of ATP in the presence of all the uremic toxins. The utilization of ATP, as indicated by active transmembrane potassium transport, was also unaffected by the above listed guanidines and phenols. It is concluded that the in vitro inhibition of ADP-induced platelet aggregation by the guanidines and phenols studied is not due to inhibition of production or utilization of ATP.

Sign in / Sign up

Export Citation Format

Share Document