scholarly journals Effects of Kynurenine Pathway Metabolites on Intracellular NAD+ Synthesis and Cell Death in Human Primary Astrocytes and Neurons

2009 ◽  
Vol 2 ◽  
pp. IJTR.S2318 ◽  
Author(s):  
Nady Braidy ◽  
Ross Grant ◽  
Bruce J Brew ◽  
Seray Adams ◽  
Tharusha Jayasena ◽  
...  
Keyword(s):  
Cell Death ◽  
Picolinic Acid ◽  
Pyridine Nucleotide ◽  
Kynurenine Pathway ◽  
Biologically Active ◽  
Active Metabolites ◽  
Nad Synthesis ◽  
Hydroxyanthranilic Acid ◽  
Dose Dependent Decrease ◽  
Dose Dependent

The kynurenine pathway (KP) is a major route of L-tryptophan catabolism resulting in the production of the essential pyridine nucleotide nicotinamide adenine dinucleotide, (NAD+). Up-regulation of the KP during inflammation leads to the release of a number of biologically active metabolites into the brain. We hypothesised that while some of the extracellular KP metabolites may be beneficial for intracellular NAD+ synthesis and cell survival at physiological concentrations, they may contribute to neuronal and astroglial dysfunction and cell death at pathophysiological concentrations. In this study, we found that treatment of human primary neurons and astrocytes with 3-hydroxyanthranilic acid (3-HAA), 3-hydroxykynurenine (3-HK), quinolinic acid (QUIN), and picolinic acid (PIC) at concentrations below 100 nM significantly increased intracellular NAD+ levels compared to non-treated cells. However, a dose dependent decrease in intracellular NAD+ levels and increased extracellular LDH activity was observed in human astrocytes and neurons treated with 3-HAA, 3-HK, QUIN and PIC at concentrations >100 nM and kynurenine (KYN), at concentrations above 1 μM. Intracellular NAD+ levels were unchanged in the presence of the neuroprotectant, kynurenic acid (KYNA), and a dose dependent increase in intracellular NAD+ levels was observed for TRP up to 1 mM. While anthranilic acid (AA) increased intracellular NAD+ levels at concentration below 10 μM in astrocytes. NAD+ depletion and cell death was observed in AA treated neurons at concentrations above 500 nM. Therefore, the differing responses of astrocytes and neurons to an increase in KP metabolites should be considered when assessing KP toxicity during neuroinflammation.

scholarly journals 3-Hydroxykynurenine and 3-Hydroxyanthranilic Acid Enhance the Toxicity Induced by Copper in Rat Astrocyte Culture

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Daniela Ramírez-Ortega ◽  
Alelí Ramiro-Salazar ◽  
Dinora González-Esquivel ◽  
Camilo Ríos ◽  
Benjamín Pineda ◽  
...  
Keyword(s):  
Cell Death ◽  
Copper Toxicity ◽  
Kynurenine Pathway ◽  
Ros Production ◽  
Independent Manner ◽  
Tryptophan Degradation ◽  
Mtt Reduction ◽  
Hydroxyanthranilic Acid ◽  
Rat Astrocyte ◽  
Effect Of Copper

Copper is an integral component of various enzymes, necessary for mitochondrial respiration and other biological functions. Excess copper is related with neurodegenerative diseases as Alzheimer and is able to modify cellular redox environment, influencing its functions, signaling, and catabolic pathways. Tryptophan degradation through kynurenine pathway produces some metabolites with redox properties as 3-hydroxykynurenine (3-HK) and 3-hydroxyanthranilic acid (3-HANA). The imbalance in their production is related with some neuropathologies, where the common factors are oxidative stress, inflammation, and cell death. This study evaluated the effect of these kynurenines on the copper toxicity in astrocyte cultures. It assessed the CuSO4effect, alone and in combination with 3-HK or 3-HANA on MTT reduction, ROS production, mitochondrial membrane potential (MMP), GHS levels, and cell viability in primary cultured astrocytes. Also, the chelating copper effect of 3-HK and 3-HANA was evaluated. The results showed that CuSO4 decreased MTT reduction, MMP, and GSH levels while ROS production and cell death are increasing. Coincubation with 3-HK and 3-HANA enhances the toxic effect of copper in all the markers tested except in ROS production, which was abolished by these kynurenines. Data suggest that 3-HK and 3-HANA increased copper toxicity in an independent manner to ROS production.

scholarly journals Modulation of hemoglobin synthesis in K-562(S) cells treated with interferons

Blood ◽  
1983 ◽  
Vol 61 (6) ◽  
pp. 1146-1154
Author(s):  
L Cioe ◽  
P Meo ◽  
V Sorrentino ◽  
GB Rossi
Keyword(s):  
Cell Death ◽  
Inhibitory Effect ◽  
Low Doses ◽  
Free Medium ◽  
Hemoglobin Synthesis ◽  
Alpha Beta ◽  
K 562 Cells ◽  
Dose Dependent Decrease ◽  
Ifn Treatment ◽  
Dose Dependent

Treatment of K-562(S) cells with human interferons (HulFN) alpha, beta, or gamma results in a modulation of hemoglobin (Hb) production. When K- 562(S) cells, “induced” with butyric acid or hemin, are given low dosages of all three types of IFN, the percent benzidine-positive cells doubles. Treatment with low doses of IFN causes the acceleration and increased production of those Hb types (as shown by Cellogel analysis) that are already synthesized either in untreated or in “induced” cultures. These results were confirmed by using pure HulFN-beta, and were abrogated, for HulFN-alpha, in presence of its specific antiserum. In contrast, cultures of K-562 cells treated with either inducer and given more than 10(4) IU/ml of alpha- or beta-IFN show a dose-dependent decrease of hemoglobinization in the absence of cell death. The inhibitory effect was reversible upon removal of IFN and culture reseeding in IFN- and inducer-free medium. The significance of both sets of data is strengthened by the pronounced heterogeneity of K-562S cells with respect to their sensitivity to IFN treatment as evaluated by the establishment of the antiviral state. Apparently, one cell out of two is sensitive to IFN, which suggests that the magnitude of IFN effects described here may be larger than it appears to be from the data taken at face value.

scholarly journals Modulation of hemoglobin synthesis in K-562(S) cells treated with interferons

Blood ◽  
1983 ◽  
Vol 61 (6) ◽  
pp. 1146-1154 ◽  
Author(s):  
L Cioe ◽  
P Meo ◽  
V Sorrentino ◽  
GB Rossi
Keyword(s):  
Cell Death ◽  
Inhibitory Effect ◽  
Low Doses ◽  
Free Medium ◽  
Hemoglobin Synthesis ◽  
Alpha Beta ◽  
K 562 Cells ◽  
Dose Dependent Decrease ◽  
Ifn Treatment ◽  
Dose Dependent

Abstract Treatment of K-562(S) cells with human interferons (HulFN) alpha, beta, or gamma results in a modulation of hemoglobin (Hb) production. When K- 562(S) cells, “induced” with butyric acid or hemin, are given low dosages of all three types of IFN, the percent benzidine-positive cells doubles. Treatment with low doses of IFN causes the acceleration and increased production of those Hb types (as shown by Cellogel analysis) that are already synthesized either in untreated or in “induced” cultures. These results were confirmed by using pure HulFN-beta, and were abrogated, for HulFN-alpha, in presence of its specific antiserum. In contrast, cultures of K-562 cells treated with either inducer and given more than 10(4) IU/ml of alpha- or beta-IFN show a dose-dependent decrease of hemoglobinization in the absence of cell death. The inhibitory effect was reversible upon removal of IFN and culture reseeding in IFN- and inducer-free medium. The significance of both sets of data is strengthened by the pronounced heterogeneity of K-562S cells with respect to their sensitivity to IFN treatment as evaluated by the establishment of the antiviral state. Apparently, one cell out of two is sensitive to IFN, which suggests that the magnitude of IFN effects described here may be larger than it appears to be from the data taken at face value.

scholarly journals Novel Methylselenoesters Induce Programed Cell Death via Entosis in Pancreatic Cancer Cells

2018 ◽  
Vol 19 (10) ◽  
pp. 2849 ◽  
Author(s):  
Prajakta Khalkar ◽  
Nuria Díaz-Argelich ◽  
Juan Antonio Palop ◽  
Carmen Sanmartín ◽  
Aristi Fernandes
Keyword(s):  
Cell Death ◽  
Biologically Active ◽  
Active Metabolites ◽  
Lead Compounds ◽  
Downstream Effector ◽  
Methylseleninic Acid ◽  
Pancreatic Cancer Cells ◽  
Redox Active ◽  
Programed Cell Death ◽  
Biologically Active Metabolites

Redox active selenium (Se) compounds have gained substantial attention in the last decade as potential cancer therapeutic agents. Several Se compounds have shown high selectivity and sensitivity against malignant cells. The cytotoxic effects are exerted by their biologically active metabolites, with methylselenol (CH3SeH) being one of the key executors. In search of novel CH3SeH precursors, we previously synthesized a series of methylselenoesters that were active (GI50 < 10 µM at 72 h) against a panel of cancer cell lines. Herein, we refined the mechanism of action of the two lead compounds with the additional synthesis of new analogs (ethyl, pentyl, and benzyl derivatives). A novel mechanism for the programmed cell death mechanism for Se-compounds was identified. Both methylseleninic acid and the novel CH3SeH precursors induced entosis by cell detachment through downregulation of cell division control protein 42 homolog (CDC42) and its downstream effector β1-integrin (CD29). To our knowledge, this is the first time that Se compounds have been reported to induce this type of cell death and is of importance in the characterization of the anticancerogenic properties of these compounds.

Ecological and physiological as well as biochemical properties of representatives of the Genus sedum L.

2014 ◽  
Vol 25 (3-4) ◽  
pp. 24-33
Author(s):  
O. I. Dzjuba ◽  
M. V. Yatsenko
Keyword(s):  
Nitric Oxide ◽  
Cell Line ◽  
Methanol Extract ◽  
Hepatoma Cell ◽  
Ethanol Extract ◽  
Biochemical Properties ◽  
Biologically Active ◽  
Hepatoma Cell Line ◽  
Dependent Manner ◽  
Dose Dependent

The article deals with the history of the study and the current state of research of physiological and biochemical properties of the plant genus Sedum that are useful for human and has been used in folk medicine for many years. It was noticed that antioxidant properties of extracts from plants S. sarmentosum, S. sempervivoides, S. takesimense were caused by the presence of phenolic compounds. Methanol extract of plants S. takesimense exhibited strong scavenging activities against 2,2-diphenyl-1-picrylhydrazyl (DPPH) and superoxide radicals as well as significant inhibitory effects on lipid peroxidation and low density lipoprotein (LDL) oxidation induced by a metal ion Cu2+. Various immunomodulatory activities of various fractions of plants extracts (S. dendroideum, S. kamtschaticum, S. sarmentosum, S. telephium) are observed. It was shown that the ethanol extract of S. sarmentosum and it’s fractions suppressed specific antibody and cellular responses to ovalbumin in mice. The methanol extract of plants S. sarmentosum reduced the levels of anti-inflammatory markers, such as volume of exudates, number of polymorphonuclear leukocytes, suppressed nitric oxide synthesis in activated macrophages via suppressed induction of inducible nitric oxide synthase (iNOS). Polysaccharides fractions from plants S. telephium inducing productions of tumor necrosis factor alpha (TNF-α), increasing the intensity of phagocytosis in vitro and in vivo. Methanol extract from the whole part of S. kamtschaticum strongly inhibit PGE2 production from lipopolysaccharide-induced RAW 264.7 cells, a mouse macrophage cell line via modulating activity in gene expression of the enzyme cyclooxygenase-2 (COX-2). The methanol extract of plants S. sarmentosum and the major kaempferol glycosides from S. dendroideum have antinociceptive activity. It was noticed that anti-adipogenic activity of extracts from plants S. kamtschaticum were caused by inhibition of peroxisome-proliferator-activated receptor γ (PPARγ) expression and it’s dependent target genes, such as genes encoding adipocyte protein 2 (аР2), lipoprotein lipase (LPL), adiponectin and CD36. Polysaccharides fractions from S. telephium cause inhibition of cell adhesion of human fibroblast (MRC5) to laminin and fibronectin via interfere with integrin-mediated cell behaviour and they contributed to the role of polysaccharides in cell-matrix interaction. The methanol extract of plants S. sarmentosum exhibited a significant inhibitory activity in the chick embryo chorioallantoic membrane angiogenesis in a dose-dependent manner. The crude alkaloid fraction of S. sarmentosum caused a dose-dependent inhibition of cell proliferation on murine hepatoma cell line BNL CL.2 and human hepatoma cell line HepG2 without necrosis or apoptosis. Alkaloids from plants S. sarmentosum may improve survival of hepatoma patients via the inhibition of excessive growth of tumor cells. Plant’s juices have antiviral activity (S. sarmentosum, S. spurium, S. stahlii). Crude ethanol extract S. praealtum have spermicidal activity of the in mice and a relevant inhibitory effect of aqueous extract on human spermatozoa motility as well as an anti-fertilizing activity in rats. Hepatoprotective triterpenes, e.g., δ-amyrone, 3-epi-δ-amyrin, δ-amyrin and sarmentolin were isolated from S. sarmentosum. 2- and 2,6-substituted piperidine alkaloids (e.g., norsedamine, allosedridine, sedamine, allosedamine) are observed in plants S. acre, which in the presence of data on the use of pyridine and piperidine derivatives for treating neurodegenerative diseases (e.g., Alzheimer's disease), points on the promising research in this area. Taking into account that biologically active compounds are accumulated in the aboveground vegetative organs of plants of Sedum, the prospects of further study of the use of Sedum for the purposes of biotechnology and in the pharmaceutical industry becomes apparent. This work extends the existing views regarding the use of plants Sedum.

Metabolomics of Healthy Berry Fruits

2019 ◽  
Vol 25 (37) ◽  
pp. 4888-4902 ◽  
Author(s):  
Gilda D'Urso ◽  
Sonia Piacente ◽  
Cosimo Pizza ◽  
Paola Montoro
Keyword(s):  
Biological Activities ◽  
Biologically Active ◽  
In Vivo Studies ◽  
Bioactive Metabolites ◽  
Active Metabolites ◽  
Positive Effects ◽  
Cell Functions ◽  
Berry Fruits

The consumption of berry-type fruits has become very popular in recent years because of their positive effects on human health. Berries are in fact widely known for their health-promoting benefits, including prevention of chronic disease, cardiovascular disease and cancer. Berries are a rich source of bioactive metabolites, such as vitamins, minerals, and phenolic compounds, mainly anthocyanins. Numerous in vitro and in vivo studies recognized the health effects of berries and their function as bioactive modulators of various cell functions associated with oxidative stress. Plants have one of the largest metabolome databases, with over 1200 papers on plant metabolomics published only in the last decade. Mass spectrometry (MS) and NMR (Nuclear Magnetic Resonance) are the most important analytical technologies on which the emerging ''omics'' approaches are based. They may provide detection and quantization of thousands of biologically active metabolites from a tissue, working in a ''global'' or ''targeted'' manner, down to ultra-trace levels. In the present review, we highlighted the use of MS and NMR-based strategies and Multivariate Data Analysis for the valorization of berries known for their biological activities, important as food and often used in the preparation of nutraceutical formulations.

Synthesis, Spectral Characterization, Antibacterial and Anticancer Activity of some Titanium Complexes

2018 ◽  
Vol 18 (5) ◽  
pp. 739-746 ◽  
Author(s):  
Raj Kaushal ◽  
Nitesh Kumar ◽  
Archana Thakur ◽  
Kiran Nehra ◽  
Pamita Awasthi ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Death ◽  
Anticancer Activity ◽  
Cell Lines ◽  
Spectral Characterization ◽  
Mechanistic Study ◽  
Titanium Complexes ◽  
G0 Phase ◽  
Antibacterial And Anticancer Activity ◽  
Dose Dependent

Abstract: Background: After the discovery of cisplatin, first non platinum anticancer drugs having excellent efficacy were budotitane and TiCl2(cp)2 but action mechanism is not clear. Therefore, we hereby reporting synthesis and biological activities novel titanium complexes to explore their mode of action. Objectives: Synthesis, spectral characterization, antibacterial and anticancer activity of some titanium complexes. Antibacterial studies on various bacterial strains and anticancer studies on HeLa, C6, CHO cancerous cell lines have been performed. Further, the cell death mechanistic study was done on CHO cell lines. Method: Titanium complexes with and without labile groups have been synthesized by reacting of TiCl4 with nitrogen containing ligands viz. 1,2-diaminocyclohexane, 1,10-Phenanthroline, adamantylamine, 2,2'-bipyridine, 4,4'-dimethyl-2,2'-bipyridine in predetermined molar ratios. Antibacterial and anticancer studies were performed by agar well diffusion method and MTT assay respectively. Cell cycle analysis is done by using flow cytometry. Results: Complex 2 i.e TiCl2(Phen)2 showed better activity than other complexes as an antibacterial as well as anticancer agent. Phase contrast imaging indicates that observed morphological changes of cells was dose dependent. Cell death mechanistic study have shown the increase in sub G0 phase population as well as formation of blebbing and fragmentation of chromatin material which is an indicative measure of apoptosis. Conclusion: Complex 2 proved to be more effective bactericide and cytotoxic agent. Cell cycle analysis showed cell arrest in G0 phase. Apoptosis percentage was found to increase in a dose dependent manner. So, prepared titanium complexes can be put to use as an important chemotherapeutic agents.

Spices with Breast Cancer Chemopreventive and Therapeutic Potentials: A Functional Foods Based-Review

2018 ◽  
Vol 18 (2) ◽  
pp. 182-194 ◽  
Author(s):  
Aliyu Muhammad ◽  
Mohammed Auwal Ibrahim ◽  
Ochuko Lucky Erukainure ◽  
Ibrahim Malami ◽  
Auwal Adamu
Keyword(s):  
Breast Cancer ◽  
Urban Areas ◽  
Cancer Chemoprevention ◽  
Biologically Active ◽  
Active Metabolites ◽  
Rural And Urban Areas ◽  
Anticancer Properties ◽  
Rural And Urban ◽  
Breast Cancer Chemoprevention ◽  
Biologically Active Metabolites

Background: Cancer is a multifaceted metabolic disease that affects sizeable dwellers of rural and urban areas. Among the various types of cancer, mammary cancer is one of the most frequently diagnosed cancers in women. Its menace can be curbed with locally consumed spices due to their multiple bioactive phytochemicals. Aims: This review focuses on the breast cancer chemopreventive and therapeutic potentials of locally consumed spices. Methods/Results: The most commonly consumed spices with breast cancer chemopreventive and chemotherapeutic phytochemical include pepper, onions, ginger, garlic, curry and thyme containing many biologically active metabolites ranging from vitamins, fatty acids esters, polyphenols/phenolics, sulfurcontaining compounds and anthraquinones with proven antioxidant, anti-inflammatory, immuno-modulatory, antitumor and anticancer properties against breast cancer/carcinogenesis. Therefore, extracts and active principles of these spices could be explored in breast cancer chemoprevention and possibly therapeutically which may provide an avenue for reducing the risk and prevalence of breast cancer.

Sign in / Sign up

Export Citation Format

Share Document