scholarly journals Collagen metabolism as a regulator of proline dehydrogenase/proline oxidase-dependent apoptosis/autophagy

Amino Acids ◽  
2021 ◽  
Author(s):  
Jerzy Palka ◽  
Ilona Oscilowska ◽  
Lukasz Szoka
Keyword(s):  
Cell Metabolism ◽  
Underlying Mechanism ◽  
Collagen Biosynthesis ◽  
Proline Metabolism ◽  
Proline Dehydrogenase ◽  
Histone Demethylases ◽  
Proline Oxidase ◽  
Prolyl Hydroxylases ◽  
Transport Chain ◽  
And Control

AbstractRecent studies on the regulatory role of amino acids in cell metabolism have focused on the functional significance of proline degradation. The process is catalysed by proline dehydrogenase/proline oxidase (PRODH/POX), a mitochondrial flavin-dependent enzyme converting proline into ∆1-pyrroline-5-carboxylate (P5C). During this process, electrons are transferred to electron transport chain producing ATP for survival or they directly reduce oxygen, producing reactive oxygen species (ROS) inducing apoptosis/autophagy. However, the mechanism for switching survival/apoptosis mode is unknown. Although PRODH/POX activity and energetic metabolism were suggested as an underlying mechanism for the survival/apoptosis switch, proline availability for this enzyme is also important. Proline availability is regulated by prolidase (proline supporting enzyme), collagen biosynthesis (proline utilizing process) and proline synthesis from glutamine, glutamate, α-ketoglutarate (α-KG) and ornithine. Proline availability is dependent on the rate of glycolysis, TCA and urea cycles, proline metabolism, collagen biosynthesis and its degradation. It is well established that proline synthesis enzymes, P5C synthetase and P5C reductase as well as collagen prolyl hydroxylases are up-regulated in most of cancer types and control rates of collagen biosynthesis. Up-regulation of collagen prolyl hydroxylase and its exhaustion of ascorbate and α-KG may compete with DNA and histone demethylases (that require the same cofactors) to influence metabolic epigenetics. This knowledge led us to hypothesize that up-regulation of prolidase and PRODH/POX with inhibition of collagen biosynthesis may represent potential pharmacotherapeutic approach to induce apoptosis or autophagic death in cancer cells. These aspects of proline metabolism are discussed in the review as an approach to understand complex regulatory mechanisms driving PRODH/POX-dependent apoptosis/survival.

scholarly journals The effect of diminazene aceturate on cholinesterase activity in dogs with canine babesiosis

1997 ◽  
Vol 68 (4) ◽  
Author(s):  
R.J. Milner ◽  
F. Reyers ◽  
J.H. Taylor ◽  
J.S. Van den Berg
Keyword(s):  
Treatment Group ◽  
Underlying Mechanism ◽  
Time Interval ◽  
Control Groups ◽  
Canine Babesiosis ◽  
Diminazene Aceturate ◽  
Time Intervals ◽  
Significant Depression ◽  
The Difference ◽  
And Control

A clinical trial was designed to evaluate the effects of diminazene aceturate and its stabiliser antipyrine on serum pseudocholinesterase (PChE) and red blood cell acetylcholinesterase (RBC AChE) in dogs with babesiosis. The trial was conducted on naturally occurring, uncomplicated cases of babesiosis (n = 20) that were randomly allocated to groups receiving a standard therapeutic dose of diminazene aceturate with antipyrine stabiliser (n = 10) or antipyrine alone (n = 10). Blood was drawn immediately before and every 15 minutes for 1 hour after treatment. Plasma PChE showed a 4 % decrease between 0 and 60 min within the treatment group (p < 0.05). No statistically significant differences were found between the treatment and control groups at any of the time intervals for PChE. There was an increase in RBC AChE activity at 15 min in the treatment group (p < 0.05). No significant differences were found between the treatment and control groups at any time interval for RBC AChE. In view of the difference in PChE, samples from additional, new cases (n = 10) of canine babesiosis were collected to identify the affect of the drug over 12 hours. No significant depression was identified over this time interval. The results suggests that the underlying mechanism in producing side-effects, when they do occur, is unlikely to be through cholinesterase depression.

Wheel Squeal Control With Keltrack Liquid Friction Modifier and Protector Trackside Application: Theory and Practice

2001 ◽  
Author(s):  
Donald T. Eadie ◽  
Marco Santoro ◽  
Ward Powell
Keyword(s):  
Underlying Mechanism ◽  
Practical Experience ◽  
Interface Layer ◽  
Application Rate ◽  
Sound Level ◽  
Theory And Practice ◽  
Friction Modifier ◽  
Friction Control ◽  
Lateral Creep ◽  
And Control

Abstract Wheel squeal is a source of continuing concern for many railroads and transits, as well as for their neighbours. The underlying mechanism for squeal noise has been well understood in the literature for some time. However an integrated abatement method addressing the underlying cause of the problem has not previously been reported. This paper describes practical experience using a water-based liquid High Positive Friction Modifier (Keltrack) applied using a Top of Rail trackside applicator (Portec Protector). This proprietary friction modifier and delivery equipment have been co-developed to provide an optimized product / delivery system that gives significant reduction of wheel squeal in curves. Wheels experiencing lateral creep in curves are subject to roll-slip oscillations as a result of the frictional characteristics of the interface layer between the wheel and rail. These roll-slip oscillations are amplified in the wheel web leading to the familiar squeal. Providing a thin film of material between the wheel and rail with positive friction characteristics can both in theory and practice greatly reduce the magnitude of these oscillations. The friction control characteristics of Keltrack allow the material to be delivered to the top of both rails without compromising traction or braking. Delivery of Keltrack to the contact patch is achieved with a proprietary top of rail electric trackside applicator, the Portec Protector. Key equipment features include top of rail bar design optimized for accurate and precise delivery, and control system features. The equipment is placed at the entrance to curves, and the friction modifier is carried down into the curve by the passing wheels. Application rate is optimized by control of the axle count between pump activations, and by the length of pump activation. The material is delivered to the top of both rails for optimum friction control. The integrated product / equipment technology is now successfully controlling noise at more than twenty transit sites. Typical sound level reduction is 10–15 dB, in some cases as high as 20 dB, depending on the initial sound level. Two case studies are presented illustrating the effectiveness of this technology.

The Dynamic Metastases of Human Ovarian Carcinoma to Grading Lymph Nodes in Mouse Model

2020 ◽  
Author(s):  
Licheng Du ◽  
Fenghua Kong ◽  
Qing Yang ◽  
Yaqiong Li ◽  
Peikai Ding ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Tumor Growth ◽  
Lymph Nodes ◽  
Ovarian Carcinoma ◽  
Underlying Mechanism ◽  
Computer Assisted ◽  
Primary Tumors ◽  
Lymphogenous Metastasis ◽  
Cell Dissemination ◽  
And Control

Abstract Background：Lymphogenous metastasis, one of the most common dissemination routes for ovarian carcinoma, predicts a poor prognosis and relates to most cancer-related death. Now there were no effective therapy and control methods for ovarian carcinoma. Hence, it is necessary to build an animal model of lymph node metastasis in ovarian cancer to seek for the tools to find effective treatments. Our purpose of this study was to investigate the tumor cell dissemination of ovarian carcinoma to the gradient lymph nodes of nude mice and its possible mechanism. Methods: The mice models of VEGF-D over-expressed were built and the tumor growth and sentinel lymph nodes were evaluated weekly, while the visible lymph nodes and tumor masses were excised for histological examination using HE examination. Then Evan’s Blue was conducted to observe the unveil lymphatic network. Subsequently, immunohistochemistry was performed to check the expression of relative genes. Meanwhile, microvessel counting was performed within the tumor tissues and measured using computer assisted morphometric analysis.Results: The over-expression of VEGF-D promoted the tumor growth of ovarian carcinoma, facilitated the hyperplasia of tumor lymphatic and increased the intratumoral lymphatic vessel density. Besides, the up-regulation of VEGF-D induced the expression of MMP-2, which might be the underlying mechanism for the lymph metastasis in ovarian cancer. Conclusion: It was a step-by-step progression from the inoculation of cancer cells, to the proliferation of the primary tumors, and then to the lymphatic metastases, in which VEGF-D and MMP-2 played vital roles.

scholarly journals hnRNPA2/B1 Ameliorates LPS-Induced Endothelial Injury through NF-κB Pathway and VE-Cadherin/β-Catenin Signaling Modulation In Vitro

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Yi Chen ◽  
Dan Tang ◽  
Linjie Zhu ◽  
Tianjie Yuan ◽  
Yingfu Jiao ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Inflammatory Responses ◽  
Umbilical Vein ◽  
Cell Metabolism ◽  
Endothelial Permeability ◽  
Underlying Mechanism ◽  
Endothelial Injury ◽  
Inflammatory Factors ◽  
Barrier Dysfunction

Heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2/B1) is a protein involved in the regulation of RNA processing, cell metabolism, migration, proliferation, and apoptosis. However, the effect of hnRNPA2/B1 on injured endothelial cells (ECs) remains unclear. We investigated the effect of hnRNPA2/B1 on lipopolysaccharide- (LPS-) induced vascular endothelial injury in human umbilical vein endothelial cells (HUVECs) and the underlying mechanisms. LPS was used to induce EC injury, and the roles of hnRNPA2/B1 in EC barrier dysfunction and inflammatory responses were measured by testing endothelial permeability and the expression of inflammatory factors after the suppression and overexpression of hnRNPA2/B1. To explore the underlying mechanism by which hnRNPA2/B1 regulates endothelial injury, we studied the VE-cadherin/β-catenin pathway and NF-κB activation in HUVECs. The results showed that hnRNPA2/B1 was elevated in LPS-stimulated HUVECs. Moreover, knockdown of hnRNPA2/B1 aggravated endothelial injury by increasing EC permeability and promoting the secretion of the inflammatory cytokines TNF-α, IL-1β, and IL-6. Overexpression of hnRNPA2/B1 can reduce the permeability and inflammatory response of HUVEC stimulated by LPS in vitro, while increasing the expression of VE-Cadherin and β-catenin. Furthermore, the suppression of hnRNPA2/B1 increased the LPS-induced NF-κB activation and reduced the VE-cadherin/β-catenin pathway. Taken together, these results suggest that hnRNPA2/B1 can regulate LPS-induced EC damage through regulating the NF-κB and VE-cadherin/β-catenin pathways.

scholarly journals Cancer Alters the Metabolic Fingerprint of Extracellular Vesicles

Cancers ◽  
2020 ◽  
Vol 12 (11) ◽  
pp. 3292
Author(s):  
Mari Palviainen ◽  
Kirsi Laukkanen ◽  
Zeynep Tavukcuoglu ◽  
Vidya Velagapudi ◽  
Olli Kärkkäinen ◽  
...  
Keyword(s):  
Cell Lines ◽  
Cancer Cell ◽  
Extracellular Vesicles ◽  
Western Blotting ◽  
Cell Metabolism ◽  
Cancer Cell Lines ◽  
Cancerous Cell ◽  
Metabolic Fingerprint ◽  
And Control

Cancer alters cell metabolism. How these changes are manifested in the metabolite cargo of cancer-derived extracellular vesicles (EVs) remains poorly understood. To explore these changes, EVs from prostate, cutaneous T-cell lymphoma (CTCL), colon cancer cell lines, and control EVs from their noncancerous counterparts were isolated by differential ultracentrifugation and analyzed by nanoparticle tracking analysis (NTA), electron microscopy (EM), Western blotting, and liquid chromatography-mass spectrometry (LC-MS). Although minor differences between the cancerous and non-cancerous cell-derived EVs were observed by NTA and Western blotting, the largest differences were detected in their metabolite cargo. Compared to EVs from noncancerous cells, cancer EVs contained elevated levels of soluble metabolites, e.g., amino acids and B vitamins. Two metabolites, proline and succinate, were elevated in the EV samples of all three cancer types. In addition, folate and creatinine were elevated in the EVs from prostate and CTCL cancer cell lines. In conclusion, we present the first evidence in vitro that the altered metabolism of different cancer cells is reflected in common metabolite changes in their EVs. These results warrant further studies on the significance and usability of this metabolic fingerprint in cancer.

scholarly journals Vitamin C as a Modulator of the Response to Cancer Therapy

Molecules ◽  
2019 ◽  
Vol 24 (3) ◽  
pp. 453 ◽  
Author(s):  
Wiktoria Blaszczak ◽  
Wojciech Barczak ◽  
Julia Masternak ◽  
Przemysław Kopczyński ◽  
Anatoly Zhitkovich ◽  
...  
Keyword(s):  
Vitamin C ◽  
Cancer Cells ◽  
Aerobic Glycolysis ◽  
Cell Metabolism ◽  
Experimental Studies ◽  
Reactive Oxygen Species Generation ◽  
Prolyl Hydroxylases ◽  
Beneficial Effects ◽  
Preferential Uptake ◽  
High Doses

Ascorbic acid (vitamin C) has been gaining attention as a potential treatment for human malignancies. Various experimental studies have shown the ability of pharmacological doses of vitamin C alone or in combinations with clinically used drugs to exert beneficial effects in various models of human cancers. Cytotoxicity of high doses of vitamin C in cancer cells appears to be related to excessive reactive oxygen species generation and the resulting suppression of the energy production via glycolysis. A hallmark of cancer cells is a strongly upregulated aerobic glycolysis, which elevates its relative importance as a source of ATP (Adenosine 5′-triphosphate). Aerobic glycolysis is maintained by a highly increased uptake of glucose, which is made possible by the upregulated expression of its transporters, such as GLUT-1, GLUT-3, and GLUT-4. These proteins can also transport the oxidized form of vitamin C, dehydroascorbate, permitting its preferential uptake by cancer cells with the subsequent depletion of critical cellular reducers as a result of ascorbate formation. Ascorbate also has a potential to affect other aspects of cancer cell metabolism due to its ability to promote reduction of iron(III) to iron(II) in numerous cellular metalloenzymes. Among iron-dependent dioxygenases, important targets for stimulation by vitamin C in cancer include prolyl hydroxylases targeting the hypoxia-inducible factors HIF-1/HIF-2 and histone and DNA demethylases. Altered metabolism of cancer cells by vitamin C can be beneficial by itself and promote activity of specific drugs.

scholarly journals Enhanced sensitivity to acute angiotensin II is testosterone dependent in adult male growth-restricted offspring

2010 ◽  
Vol 298 (5) ◽  
pp. R1421-R1427 ◽  
Author(s):  
Norma B. Ojeda ◽  
Thomas P. Royals ◽  
Joshua T. Black ◽  
John Henry Dasinger ◽  
Jeremy M. Johnson ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Adult Male ◽  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Underlying Mechanism ◽  
Male Rats ◽  
Ang Ii ◽  
Enhanced Sensitivity ◽  
And Control

Placental insufficiency results in intrauterine growth restriction (IUGR) and hypertension in adult male growth-restricted rats. Although renal ANG II and plasma renin activity do not differ between growth-restricted and control rats, blockade of the renin-angiotensin system (RAS) abolishes hypertension in growth-restricted rats, suggesting that the RAS contributes to IUGR-induced hypertension. Moreover, castration abolishes hypertension in growth-restricted rats, indicating an important role for testosterone. Therefore, we hypothesized that enhanced responsiveness to ANG II contributes to hypertension in this model of IUGR and that androgens may play a pivotal role in this enhanced response. Physiological parameters were determined at 16 wk of age in male rats pretreated with enalapril (40 mg·kg−1·day−1) for 1 wk. Baseline blood pressures were similar between growth-restricted (112 ± 3 mmHg) and control (110 ± 2 mmHg) rats; however, an enhanced pressor response to acute ANG II (100 ng·kg−1·min−1 for 30 min) was observed in growth-restricted (160 ± 2 mmHg) vs. control (136 ± 2 mmHg; P < 0.05) rats. Castration abolished the enhanced pressor response to acute ANG II in growth-restricted (130 ± 2 mmHg) rats with no significant effect on blood pressure in controls (130 ± 2 mmHg). Blood pressure was increased to a similar extent above baseline in response to acute phenylephrine (100 μg/min) in control (184 ± 5 mmHg) and growth-restricted (184 ± 8 mmHg) rats, suggesting the enhanced pressor response in growth-restricted rats is ANG II specific. Thus, these results suggest that growth-restricted rats exhibit an enhanced responsiveness to ANG II that is testosterone dependent and indicate that the RAS may serve as an underlying mechanism in mediating hypertension programmed in response to IUGR.

Laboratory studies on dispersion behaviour of adult beetles in grain. XII.—The effect of isolated pockets of damp and mouldy wheat on Cryptolestes ferrugineus (Steph.) (Coleoptera, Cucujidae)

1965 ◽  
Vol 55 (4) ◽  
pp. 673-680 ◽  
Author(s):  
Gordon Surtees
Keyword(s):  
Moisture Content ◽  
Underlying Mechanism ◽  
Cryptolestes Ferrugineus ◽  
Dynamic Nature ◽  
Physical Conditions ◽  
Cent Moisture ◽  
Structure Dispersion ◽  
Insect Populations ◽  
Aspergillus Candidus ◽  
And Control

The effects of pockets of damp wheat upon the spatial structure (dispersion) of experimental populations of adults of Cryptolestes ferrugineus (Steph.) were investigated in the laboratory. Isolated pockets of non-mouldy wheat of 18 per cent, moisture content (85 per cent. R.H.) and of equally moist wheat supporting a mould flora (mainly Aspergillus candidus) were placed in a larger bulk of wheat of 14 per cent, moisture content (70 per cent. R.H.) at 25°C. One hundred beetles were released at the centre of the top surface of the bulk, and their dispersion within it was observed one week later. The method used allowed the entire bulk (25 kg.) to be quickly broken down so that the relative numbers of individuals in each of the 64 cubes of which it was composed could be recorded. Using other apparatus, the responses of single, isolated individuals to these physical conditions were analysed.Insects reared at 25°C. and 70 per cent. R.H. accumulated to an equal extent in the pockets of damp wheat irrespective of whether it was mouldy or not. Insects in a preferendum arena went to the drier side, i.e., to 70 per cent, as opposed to 85 per cent. R.H., and the underlying mechanism was found to be a klinokinetic response to humidity. Maintaining insects at 40 or 85 per cent. R.H. for 14 days before testing did not alter their dispersion behaviour in bulks of grain; maintenance at 40 per cent. R.H. did not alter their response to humidity in a preferendum arena, but at 80 per cent. R.H. it was abolished.A study of oviposition behaviour showed that when there was a choice between wheat of 18 and 14 per cent, moisture content, nearly all the eggs were laid in the damper grain, both when it was mouldy and when it was not. It is considered that oviposition requirements, and to some extent trophic behaviour patterns, over-ride the hygrokinetic response when wheat is damp or damaged, but that under field conditions, where the presence of dust and broken grain throughout the bulk provide conditions suited for oviposition and feeding, accumulations due solely to hygrokinesis may occur in the drier parts of a bulk.The results are discussed in relation to the ecology of the species in grain and to its detection and control; and evidence from this and other studies is discussed in relation to the dynamic nature of spatial organisation of insect populations in grain.

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