scholarly journals Ionophore Ability of Carnosine and Its Trehalose Conjugate Assists Copper Signal in Triggering Brain-Derived Neurotrophic Factor and Vascular Endothelial Growth Factor Activation In Vitro

2021 ◽  
Vol 22 (24) ◽  
pp. 13504
Author(s):  
Irina Naletova ◽  
Valentina Greco ◽  
Sebastiano Sciuto ◽  
Francesco Attanasio ◽  
Enrico Rizzarelli
Keyword(s):  
Tyrosine Kinase ◽  
Protective Action ◽  
Protective Role ◽  
Copper Binding ◽  
Molecular Features ◽  
Mammalian Tissues ◽  
Kinase Cascade ◽  
High Concentrations ◽  
Endothelial Growth Factor

l-carnosine (β-alanyl-l-histidine) (Car hereafter) is a natural dipeptide widely distributed in mammalian tissues and reaching high concentrations (0.7–2.0 mM) in the brain. The molecular features of the dipeptide underlie the antioxidant, anti-aggregating and metal chelating ability showed in a large number of physiological effects, while the biological mechanisms involved in the protective role found against several diseases cannot be explained on the basis of the above-mentioned properties alone, requiring further research efforts. It has been reported that l-carnosine increases the secretion and expression of various neurotrophic factors and affects copper homeostasis in nervous cells inducing Cu cellular uptake in keeping with the key metal-sensing system. Having in mind this l-carnosine ability, here we report the copper-binding and ionophore ability of l-carnosine to activate tyrosine kinase cascade pathways in PC12 cells and stimulate the expression of BDNF. Furthermore, the study was extended to verify the ability of the dipeptide to favor copper signaling inducing the expression of VEGF. Being aware that the potential protective action of l-carnosine is drastically hampered by its hydrolysis, we also report on the behavior of a conjugate of l-carnosine with trehalose that blocks the carnosinase degradative activity. Overall, our findings describe a copper tuning effect on the ability of l-carnosine and, particularly its conjugate, to activate tyrosine kinase cascade pathways.

Protective effects of selenium against sister chromatid exchange induced by AFG 1 in human lymphocytes in vitro

2010 ◽  
Vol 30 (6) ◽  
pp. 515-519
Author(s):  
Lokman Alpsoy ◽  
Elif Kotan ◽  
Abdulgani Tatar ◽  
Guleray Agar
Keyword(s):  
Sister Chromatid ◽  
Sister Chromatid Exchange ◽  
Human Lymphocytes ◽  
Protective Role ◽  
Blood Cultures ◽  
Protective Effects ◽  
Low Concentrations ◽  
High Concentrations

Aflatoxins have been shown to be hepatotoxic, carcinogenic, mutagenic and teratogenic to different species of animals. Besides, at low concentrations, Selenium (Se4+) is antimutagenic and anticarcinogenic while it is toxic, mutagenic and carcinogenic at high concentrations. In this study, we aimed to evaluate the effect of Se4+ against aflatoxin GAFG1 (AFG1) on blood cultures in relation to induction of sister chromatid exchange (SCE). The results showed that at 0.4 and 0.8 parts per million (ppm) concentration of AFG1, the frequency of SCE increased in cultured human lymphocytes. When different concentration of Se4+ (0.08 and 8 ppm) were added to AFG1, the frequencies of SCE decreased. Howewer, when 800 ppm concentration of Se4+ together with 0.08 ppm AFG1 were added to cell division inhibited in the cultures. Results suggested that Se4+ could effectively inhibit AFG1-induced SCE. Besides, the protective role of Se4+ against AFG1-induced SCE is probably related to its doses.

scholarly journals The contribution of paraoxonase 1 and myeloperoxidase to HDL-cholesterol functionality

2016 ◽  
Vol 8 (1) ◽  
pp. 51-57 ◽  
Author(s):  
Marzena Malara ◽  
Anna Kęska ◽  
Grażyna Lutosławska
Keyword(s):  
Ldl Cholesterol ◽  
Scientific Evidence ◽  
Protective Action ◽  
Hdl Cholesterol ◽  
Protective Role ◽  
Plasma Lipoproteins ◽  
Paraoxonase 1 ◽  
Increased Risk

SummaryThe purpose of this study was to analyse the scientific evidence concerning the effects of two enzymes – paraoxonase 1 and myeloperoxidase – on the functions of HDL-cholesterol. It is well documented that disturbed circulating lipoproteins (a high total and high LDL-cholesterol, and low HDL-cholesterol) bring about atherosclerosis and an increased risk of cardiovascular disease (CVD) which is recognised as the main cause of death all around the world. In consequence, numerous studies have focused on procedures which will improve the plasma lipoproteins profile by decreasing the total cholesterol and the LDL-cholesterol (LDL-C) and increasing the HDL-cholesterol (HDL-C). However, the anti-atherogenic role of HDL-C has been challenged in studies showing that genetically elevated HDL-cholesterol does not offer protection against CVD. Moreover, it has been found that raising the circulating HDL-cholesterol fails to reduce atherosclerosis. The doubts concerning the protective role of HDL-C have been supported by in vitro studies which indicate that the HDL-C from patients with atherosclerosis does not have a protective action, but does stimulate inflammation and free radical synthesis. The above data suggests that HDL-C, commonly recognised as protective against atherosclerosis, in some circumstances becomes pro-atherogenic, and is thus dysfunctional. Our review focuses on two enzymes – paraoxonase 1 (PON1) and myeloperoxidase (MPO) – which markedly affect the properties of HDL-C and contribute to its anti – or pro-atherogenic activity. Moreover, the effects of the diet and physical activity on PON1 and MPO are summarised with respect to the HDL-C functionality.

scholarly journals Duplicate VegfA genes and orthologues of the KDR receptor tyrosine kinase family mediate vascular development in the zebrafish

Blood ◽  
2007 ◽  
Vol 110 (10) ◽  
pp. 3627-3636 ◽  
Author(s):  
Nathan Bahary ◽  
Katsutoshi Goishi ◽  
Carsten Stuckenholz ◽  
Gerhard Weber ◽  
Jocelyn LeBlanc ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Receptor Tyrosine Kinase ◽  
Vascular Development ◽  
Circulatory System ◽  
Vascular Effects ◽  
Type Iii ◽  
Culture Cells ◽  
Strong Homology ◽  
Endothelial Growth Factor

Abstract Vascular endothelial growth factor A (VEGFA) and the type III receptor tyrosine kinase receptors (RTKs) are both required for the differentiation of endothelial cells (vasculogenesis) and for the sprouting of new capillaries (angiogenesis). We have isolated a duplicated zebrafish VegfA locus, termed VegfAb, and a duplicate RTK locus with homology to KDR/FLK1 (named Kdrb). Morpholino-disrupted VegfAb embryos develop a normal circulatory system until approximately 2 to 3 days after fertilization (dpf), when defects in angiogenesis permit blood to extravasate into many tissues. Unlike the VegfAa121 and VegfAa165 isoforms, the VegfAb isoforms VegfAb171 and VegfAb210 are not normally secreted when expressed in mammalian tissue culture cells. The Kdrb locus encodes a 1361–amino acid transmembrane receptor with strong homology to mammalian KDR. Combined knockdown of both RTKs leads to defects in vascular development, suggesting that they cooperate in mediating the vascular effects of VegfA in zebrafish development. Both VegfAa and VegfAb can individually bind and promote phosphorylation of both Flk1 (Kdra) and Kdrb proteins in vitro. Taken together, our data support a model in the zebrafish, in which duplicated VegfA and multiple type III RTKs mediate vascular development.

scholarly journals Activation of Ciona sperm motility: phosphorylation of dynein polypeptides and effects of a tyrosine kinase inhibitor

1991 ◽  
Vol 100 (4) ◽  
pp. 815-824 ◽  
Author(s):  
C.S. Dey ◽  
C.J. Brokaw
Keyword(s):  
Cyclic Amp ◽  
Tyrosine Kinase ◽  
Kinase Inhibitor ◽  
Random Copolymer ◽  
Dynein Light Chain ◽  
Protein Switch ◽  
Kinase Cascade ◽  
Dependent Protein

A high molecular mass dynein ATPase polypeptide and a 18–20 kDa dynein light chain of Ciona sperm flagella are phosphorylated during in vivo activation of motility or in vitro activation of motility by incubation with cyclic AMP. A similar level of phosphorylation of these proteins is obtained by incubation of washed, demembranated spermatozoa with catalytic subunit of cyclic AMP-dependent protein kinase, under conditions where there is no activation of motility until a supernatant component is added. Therefore, phosphorylation of these dynein polypeptides is not sufficient for activation of motility. Activation of motility in vitro by incubation with cyclic AMP can be completely inhibited by a random copolymer of glutamate and tyrosine that inhibits tyrosine kinase activity. Under these conditions, much of the protein phosphorylation associated with activation of motility is also inhibited. These new results suggest that regulation of motility of these spermatozoa may involve a multicomponent kinase cascade rather than a simple phosphorylation of a protein ‘switch’ by the cyclic AMP-dependent kinase. A 53 kDa axonemal phosphoprotein band, identified as band M1, shows the strongest correlation with activation of motility in these experiments.

scholarly journals Canstatin represses glioma growth by inhibiting formation of VM-like structures

2021 ◽  
Vol 12 (1) ◽  
pp. 309-319
Author(s):  
Yuqiang Ma ◽  
Tao Wu ◽  
Houjie Zhou ◽  
Guilu He ◽  
Yifei Li ◽  
...  
Keyword(s):  
Vasculogenic Mimicry ◽  
Angiogenesis Inhibitor ◽  
Inhibitory Effect ◽  
Protective Role ◽  
Tube Formation ◽  
Vascular Endothelial ◽  
Glioma Growth ◽  
Endothelial Growth Factor

Abstract Vasculogenic mimicry (VM) is different from classical tumor angiogenesis and does not depend on endothelial cells. VM is closely related to the prognosis of various cancers. Canstatin was first identified as an endogenous angiogenesis inhibitor. In the present study, the inhibitory effect of canstatin on VM formation was evaluated. Human glioblastoma cell lines U87 and U251 were letivirally transduced to overexpress canstatin gene or GFP as control. In vitro assays showed that canstatin overexpression reduced the tube formation of U87 and U251 cells in Matrigel. A xenograft glioma model was created by subcutaneous injection of lentivirally modified U87 cells into nude mice. The results of in vivo experiments showed that canstatin gene introduction inhibited the growth of glioma xenografts. In tumor xenografts overexpressing canstatin, U87-mediated formation of VM-like structures and VM-related VEGF (vascular endothelial growth factor) expression were remarkably reduced. Canstatin overexpression also decreased the phosphorylation of Akt and reduced the expression of Survivin in vitro. In addition, HIF-1α production and MMP-2 secretion were decreased by canstatin overexpression. Therefore, these results suggested a protective role of canstatin during VM-like structure formation of glioma probably via inhibiting signaling pathways inducing vasculogenic mimicry.

scholarly journals Protective Role of Catechin and Quercetin in Sodium Benzoate-Induced Lipid Peroxidation and the Antioxidant System in Human ErythrocytesIn Vitro

2014 ◽  
Vol 2014 ◽  
pp. 1-6 ◽  
Author(s):  
Gamze Yetuk ◽  
Dilek Pandir ◽  
Hatice Bas
Keyword(s):  
Oxidative Stress ◽  
Lipid Peroxidation ◽  
Sodium Benzoate ◽  
Protective Role ◽  
Food Additive ◽  
Human Erythrocytes ◽  
Low Concentrations ◽  
High Concentrations

The aim of this study was to evaluate the protective effect of catechin and quercetin in sodium benzoate- (SB-) induced oxidative stress in human erythrocytesin vitro. For this, the effects of SB (6.25, 12.5, 25, 50, and 100 μg/mL), catechin (10 μM), and quercetin (10 μM) on lipid peroxidation (LPO) and the activities of SOD, CAT, GPx, and GST were studied. Significantly higher LPO and lower activities of antioxidant enzymes were observed with the increasing concentrations of SB. Catechin or quercetin protected the erythrocytes against SB-induced toxicity only at low concentrations of SB. The presence of catechin or quercetin at 10 μM have no effect on SB-induced toxicity at high concentrations of SB (50 and 100 μg/mL). In conclusion, SB may cause oxidative stress as food additive in human erythrocytesin vitro. So, it appears that our findings provide evidence for the protection of erythrocytes from SB that could be considered for further studies.

scholarly journals Design, synthesis, and antitumor activity of novel benzoheterocycle derivatives as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase

2020 ◽  
Vol 44 (5-6) ◽  
pp. 286-294
Author(s):  
Yangyang Ding ◽  
Kai Liu ◽  
Xinyu Zhao ◽  
Yingtao Lv ◽  
Rilei Yu ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Growth Factor ◽  
Antitumor Activity ◽  
Tyrosine Kinase ◽  
Human Cancer ◽  
Umbilical Vein ◽  
Growth Factor Receptor ◽  
Vascular Endothelial ◽  
Endothelial Growth Factor

The vascular endothelial growth factor receptor-2 signaling pathway promotes the formation of new blood vessels, and vascular endothelial growth factor receptor-2 tyrosine kinase exists in both active and inactive conformations. Novel indole–benzimidazole and indole–benzothiazole derivatives joined by different linkers are designed and synthesized as inhibitors of vascular endothelial growth factor receptor-2 tyrosine kinase. All the synthesized compounds were evaluated for their cytotoxicity against four human cancer cell lines (HeLa, HT29, A549, and MDA-MB-435) and human umbilical vein endothelial cell. Meanwhile, the inhibitory activities against vascular endothelial growth factor receptor-2 are estimated in vitro and the binding interactions with dual conformations of vascular endothelial growth factor receptor-2 tyrosine kinase are evaluated by molecular docking. Compounds 5a–c and 14 show inhibitory activity against vascular endothelial growth factor receptor-2 tyrosine kinase and promising cytotoxicity, specifically with IC50 values ranging between 0.1 and 1 μM, which imply broad-spectrum antitumor activity. These results provide a deep insight into potential structural modifications for developing potent vascular endothelial growth factor receptor-2 tyrosine kinase inhibitors.

Role of calcium in adaptive cytoprotection and cell injury induced by deoxycholate in human gastric cells

1998 ◽  
Vol 275 (2) ◽  
pp. G322-G330 ◽  
Author(s):  
Evan R. Kokoska ◽  
Gregory S. Smith ◽  
Andrew B. Wolff ◽  
Yashwant Deshpande ◽  
Christopher L. Rieckenberg ◽  
...  
Keyword(s):  
Cellular Response ◽  
Cell Injury ◽  
Protective Action ◽  
Cellular Injury ◽  
Adaptive Cytoprotection ◽  
Gastric Cells ◽  
Intracellular Ca ◽  
High Concentrations ◽  
Mild Irritant

We have developed an in vitro model of adaptive cytoprotection induced by deoxycholate (DC) in human gastric cells and have shown that pretreatment with a low concentration of DC (mild irritant, 50 μM) significantly attenuates injury induced by a damaging concentration of DC (250 μM). This study was undertaken to assess the effect of the mild irritant on changes in intracellular Ca2+ and to determine if these perturbations account for its protective action. Protection conferred by the mild irritant was lost when any of its effects on intracellular Ca2+ were prevented: internal Ca2+ store release via phospholipase C and inositol 1,4,5-trisphosphate sustained Ca2+ influx through store-operated Ca2+ channels or eventual Ca2+ efflux. We also investigated the relationship between Ca2+accumulation and cellular injury induced by damaging concentrations of DC. In cells exposed to high concentrations of DC, sustained Ca2+ accumulation as a result of extracellular Ca2+ influx, but not transient changes in intracellular Ca2+ content, appeared to precede and induce cellular injury. We propose that the mild irritant disrupts normal Ca2+ homeostasis and that this perturbation elicits a cellular response (involving active Ca2+ efflux) that subsequently provides a protective action by limiting the magnitude of intracellular Ca2+ accumulation.

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