scholarly journals Dietary flavonoids as intracellular substrates for an erythrocyte trans-plasma membrane oxidoreductase activity

2005 ◽  
Vol 94 (3) ◽  
pp. 338-345 ◽  
Author(s):  
Mara Fiorani ◽  
Augusto Accorsi
Keyword(s):  
Plasma Membrane ◽  
Antioxidant Activities ◽  
Parent Compound ◽  
Direct Interaction ◽  
Oxidoreductase Activity ◽  
Major Mechanism ◽  
Beneficial Effects ◽  
Reducing Activity ◽  
Dietary Flavonoids

The plasma membrane oxidoreductase (PMOR) activity, which mainly utilises ascorbate as intracellular electron donor, represents a major mechanism for cell-dependent reduction of extracellular oxidants and might be an important process used by the erythrocytes to keep a reduced plasma environment. We previously reported that in human erythrocytes, myricetin and quercetin act as intracellular substrates of a PMOR showing a novel mechanism whereby these flavonoids could exert beneficial effects under oxidative stress conditions. Here, we evaluated the ability of different flavonoids (quercetin, myricetin, morin, kaempferol, fisetin, catechin, luteolin, apigenin, acacetin, rutin, taxifolin, naringenin, genistein) and of two in vivoO-methylated metabolites of quercetin (isorhamnetin and tamarixetin) to be substrates of PMOR, by comparing their antioxidant capacity (i.e. direct interaction with the oxidant ferricyanide or with the free radical 1,1-diphenyl-2-picryl-hydrazil) with their ability to penetrate the erythrocytes and donate electrons to the PMOR. The results obtained indicate that, although most of the flavonoids display significant antioxidant activities, only those (quercetin, myricetin, fisetin) that combine the cathecol structure of the B ring (responsible for the reducing activity) with the 2,3 double bond and 4-oxo function of the C ring (responsible for the uptake by erythrocytes) can act as intracellular substrates for PMOR. It is of note that the metabolites of quercetin enter erythrocytes and donate electrons to the PMOR as the parent compound. The present data show a relationship between the flavonoid structures and their ability to provide electrons to the PMOR, suggesting an additional mechanism whereby dietary flavonoids may exert beneficial effects in man.

scholarly journals A novel Netrin-1–sensitive mechanism promotes local SNARE-mediated exocytosis during axon branching

2014 ◽  
Vol 205 (2) ◽  
pp. 217-232 ◽  
Author(s):  
Cortney C. Winkle ◽  
Leslie M. McClain ◽  
Juli G. Valtschanoff ◽  
Charles S. Park ◽  
Christopher Maglione ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Cortical Neurons ◽  
Direct Interaction ◽  
Vesicle Fusion ◽  
Dependent Manner ◽  
Axon Branching ◽  
Spatial Regulation ◽  
Novel Model

Developmental axon branching dramatically increases synaptic capacity and neuronal surface area. Netrin-1 promotes branching and synaptogenesis, but the mechanism by which Netrin-1 stimulates plasma membrane expansion is unknown. We demonstrate that SNARE-mediated exocytosis is a prerequisite for axon branching and identify the E3 ubiquitin ligase TRIM9 as a critical catalytic link between Netrin-1 and exocytic SNARE machinery in murine cortical neurons. TRIM9 ligase activity promotes SNARE-mediated vesicle fusion and axon branching in a Netrin-dependent manner. We identified a direct interaction between TRIM9 and the Netrin-1 receptor DCC as well as a Netrin-1–sensitive interaction between TRIM9 and the SNARE component SNAP25. The interaction with SNAP25 negatively regulates SNARE-mediated exocytosis and axon branching in the absence of Netrin-1. Deletion of TRIM9 elevated exocytosis in vitro and increased axon branching in vitro and in vivo. Our data provide a novel model for the spatial regulation of axon branching by Netrin-1, in which localized plasma membrane expansion occurs via TRIM9-dependent regulation of SNARE-mediated vesicle fusion.

scholarly journals The synaptobrevin homologue Snc2p recruits the exocyst to secretory vesicles by binding to Sec6p

2013 ◽  
Vol 202 (3) ◽  
pp. 509-526 ◽  
Author(s):  
David Shen ◽  
Hua Yuan ◽  
Alex Hutagalung ◽  
Avani Verma ◽  
Daniel Kümmel ◽  
...  
Keyword(s):  
Plasma Membrane ◽  
Direct Interaction ◽  
Secretory Vesicles ◽  
Direct Role ◽  
Vesicular Traffic ◽  
Genes Encoding ◽  
Snare Motif ◽  
Liposome Fusion

A screen for mutations that affect the recruitment of the exocyst to secretory vesicles identified genes encoding clathrin and proteins that associate or colocalize with clathrin at sites of endocytosis. However, no significant colocalization of the exocyst with clathrin was seen, arguing against a direct role in exocyst recruitment. Rather, these components are needed to recycle the exocytic vesicle SNAREs Snc1p and Snc2p from the plasma membrane into new secretory vesicles where they act to recruit the exocyst. We observe a direct interaction between the exocyst subunit Sec6p and the latter half of the SNARE motif of Snc2p. An snc2 mutation that specifically disrupts this interaction led to exocyst mislocalization and a block in exocytosis in vivo without affecting liposome fusion in vitro. Overexpression of Sec4p partially suppressed the exocyst localization defects of mutations in clathrin and clathrin-associated components. We propose that the exocyst is recruited to secretory vesicles by the combinatorial signals of Sec4-GTP and the Snc proteins. This could help to confer both specificity and directionality to vesicular traffic.

scholarly journals Identification of a cyclase-associated protein (CAP) homologue in Dictyostelium discoideum and characterization of its interaction with actin.

1996 ◽  
Vol 7 (2) ◽  
pp. 261-272 ◽  
Author(s):  
U Gottwald ◽  
R Brokamp ◽  
I Karakesisoglou ◽  
M Schleicher ◽  
A A Noegel
Keyword(s):  
Plasma Membrane ◽  
Adenylyl Cyclase ◽  
Dictyostelium Discoideum ◽  
Direct Interaction ◽  
Actin Binding ◽  
Amino Terminal ◽  
Terminal Domain ◽  
Carboxyl Terminal Domain ◽  
Carboxyl Terminal

In search for novel actin binding proteins in Dictyostelium discoideum we have isolated a cDNA clone coding for a protein of approximately 50 kDa that is highly homologous to the class of adenylyl cyclase-associated proteins (CAP). In Saccharomyces cerevisiae the amino-terminal part of CAP is involved in the regulation of the adenylyl cyclase whereas the loss of the carboxyl-terminal domain results in morphological and nutritional defects. To study the interaction of Dictyostelium CAP with actin, the complete protein and its amino-terminal and carboxyl-terminal domains were expressed in Escherichia coli and used in actin binding assays. CAP sequestered actin in a Ca2+ independent way. This activity was localized to the carboxyl-terminal domain. CAP and its carboxyl-terminal domain led to a fluorescence enhancement of pyrene-labeled G-actin up to 50% indicating a direct interaction, whereas the amino-terminal domain did not enhance. In polymerization as well as in viscometric assays the ability of the carboxyl-terminal domain to sequester actin and to prevent F-actin formation was approximately two times higher than that of intact CAP. The sequestering activity of full length CAP could be inhibited by phosphatidylinositol 4,5-bisphosphate (PIP2), whereas the activity of the carboxyl-terminal domain alone was not influenced, suggesting that the amino-terminal half of the protein is required for the PIP2 modulation of the CAP function. In profilin-minus cells the CAP concentration is increased by approximately 73%, indicating that CAP may compensate some profilin functions in vivo. In migrating D. discoideum cells CAP was enriched at anterior and posterior plasma membrane regions. Only a weak staining of the cytoplasm was observed. In chemotactically stimulated cells the protein was very prominent in leading fronts. The data suggest an involvement of D. discoideum CAP in microfilament reorganization near the plasma membrane in a PIP2-regulated manner.

scholarly journals Thyroid hormones inhibit TGF-β signaling and attenuate fibrotic responses

2016 ◽  
Vol 113 (24) ◽  
pp. E3451-E3460 ◽  
Author(s):  
Elvira Alonso-Merino ◽  
Rosa Martín Orozco ◽  
Lidia Ruíz-Llorente ◽  
Olaia A. Martínez-Iglesias ◽  
Juan Pedro Velasco-Martín ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Thyroid Hormones ◽  
Transcriptional Activation ◽  
Hormone Receptors ◽  
Target Genes ◽  
Direct Interaction ◽  
Beneficial Effects ◽  
Hormone Administration ◽  
Fibrotic Diseases

TGF-β, the most potent profibrogenic factor, acts by activating SMAD (mothers against decapentaplegic) transcription factors, which bind to SMAD-binding elements in target genes. Here, we show that the thyroid hormone triiodothyronine (T3), through binding to its nuclear receptors (TRs), is able to antagonize transcriptional activation by TGF-β/SMAD. This antagonism involves reduced phosphorylation of SMADs and a direct interaction of the receptors with SMAD3 and SMAD4 that is independent of T3-mediated transcriptional activity but requires residues in the receptor DNA binding domain. T3 reduces occupancy of SMAD-binding elements in response to TGF-β, reducing histone acetylation and inhibiting transcription. In agreement with this transcriptional cross-talk, T3 is able to antagonize fibrotic processes in vivo. Liver fibrosis induced by carbon tetrachloride is attenuated by thyroid hormone administration to mice, whereas aged TR knockout mice spontaneously accumulate collagen. Furthermore, skin fibrosis induced by bleomycin administration is also reduced by the thyroid hormones. These findings define an important function of the thyroid hormone receptors and suggest TR ligands could have beneficial effects to block the progression of fibrotic diseases.

scholarly journals Therapeutic Potential of Ursonic Acid: Comparison with Ursolic Acid

Biomolecules ◽  
2020 ◽  
Vol 10 (11) ◽  
pp. 1505
Author(s):  
Juhyeon Son ◽  
Sang Yeol Lee
Keyword(s):  
Ursolic Acid ◽  
Therapeutic Potential ◽  
Antioxidant Activities ◽  
Biological Activities ◽  
Inhibitory Effects ◽  
Beneficial Effects ◽  
Pentacyclic Triterpenoid ◽  
Naturally Occurring ◽  
Ziziphus Jujuba

Plants have been used as drugs to treat human disease for centuries. Ursonic acid (UNA) is a naturally occurring pentacyclic triterpenoid extracted from certain medicinal herbs such as Ziziphus jujuba. Since the pharmacological effects and associated mechanisms of UNA are not well-known, in this work, we attempt to introduce the therapeutic potential of UNA with a comparison to ursolic acid (ULA), a well-known secondary metabolite, for beneficial effects. UNA has a keto group at the C-3 position, which may provide a critical difference for the varied biological activities between UNA and ULA. Several studies previously showed that UNA exerts pharmaceutical effects similar to, or stronger than, ULA, with UNA significantly decreasing the survival and proliferation of various types of cancer cells. UNA has potential to exert inhibitory effects in parasitic protozoa that cause several tropical diseases. UNA also exerts other potential effects, including antihyperglycemic, anti-inflammatory, antiviral, and antioxidant activities. Of note, a recent study highlighted the suppressive potential of UNA against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Molecular modifications of UNA may enhance bioavailability, which is crucial for in vivo and clinical studies. In conclusion, UNA has promising potential to be developed in anticancer and antiprotozoan pharmaceuticals. In-depth investigations may increase the possibility of UNA being developed as a novel reagent for chemotherapy.

scholarly journals Nanotechnological Manipulation of Nutraceuticals and Phytochemicals for Healthy Purposes: Established Advantages vs. Still Undefined Risks

Polymers ◽  
2021 ◽  
Vol 13 (14) ◽  
pp. 2262
Author(s):  
Silvana Alfei ◽  
Anna Maria Schito ◽  
Guendalina Zuccari
Keyword(s):  
Food Packaging ◽  
Water Solubility ◽  
Antioxidant Activities ◽  
Food Additives ◽  
Bioactive Constituents ◽  
Beneficial Effects ◽  
Appearance Quality ◽  
Health Promoting ◽  
Related Compounds

Numerous foods, plants, and their bioactive constituents (BACs), named nutraceuticals and phytochemicals by experts, have shown many beneficial effects including antifungal, antiviral, anti-inflammatory, antibacterial, antiulcer, anti-cholesterol, hypoglycemic, immunomodulatory, and antioxidant activities. Producers, consumers, and the market of food- and plant-related compounds are increasingly attracted by health-promoting foods and plants, thus requiring a wider and more fruitful exploitation of the healthy properties of their BACs. The demand for new BACs and for the development of novel functional foods and BACs-based food additives is pressing from various sectors. Unfortunately, low stability, poor water solubility, opsonization, and fast metabolism in vivo hinder the effective exploitation of the potential of BACs. To overcome these issues, researchers have engineered nanomaterials, obtaining food-grade delivery systems, and edible food- and plant-related nanoparticles (NPs) acting as color, flavor, and preservative additives and natural therapeutics. Here, we have reviewed the nanotechnological transformations of several BACs implemented to increase their bioavailability, to mask any unpleasant taste and flavors, to be included as active ingredients in food or food packaging, to improve food appearance, quality, and resistance to deterioration due to storage. The pending issue regarding the possible toxic effect of NPs, whose knowledge is still limited, has also been discussed.

scholarly journals Echinochrome A Treatment Alleviates Fibrosis and Inflammation in Bleomycin-Induced Scleroderma

Marine Drugs ◽  
2021 ◽  
Vol 19 (5) ◽  
pp. 237
Author(s):  
Gyu-Tae Park ◽  
Jung-Won Yoon ◽  
Sang-Bin Yoo ◽  
Young-Chul Song ◽  
Parkyong Song ◽  
...  
Keyword(s):  
Antioxidant Activities ◽  
Sea Urchins ◽  
Inflammatory Cells ◽  
Serum Levels ◽  
Interferon Γ ◽  
Echinochrome A ◽  
Beneficial Effects ◽  
Dermal Thickness ◽  
Anti Inflammatory

Scleroderma is an autoimmune disease caused by the abnormal regulation of extracellular matrix synthesis and is activated by non-regulated inflammatory cells and cytokines. Echinochrome A (EchA), a natural pigment isolated from sea urchins, has been demonstrated to have antioxidant activities and beneficial effects in various disease models. The present study demonstrates for the first time that EchA treatment alleviates bleomycin-induced scleroderma by normalizing dermal thickness and suppressing collagen deposition in vivo. EchA treatment reduces the number of activated myofibroblasts expressing α-SMA, vimentin, and phosphorylated Smad3 in bleomycin-induced scleroderma. In addition, it decreased the number of macrophages, including M1 and M2 types in the affected skin, suggesting the induction of an anti-inflammatory effect. Furthermore, EchA treatment markedly attenuated serum levels of inflammatory cytokines, such as tumor necrosis factor-α and interferon-γ, in a murine scleroderma model. Taken together, these results suggest that EchA is highly useful for the treatment of scleroderma, exerting anti-fibrosis and anti-inflammatory effects.

scholarly journals Dietary Flavonoids for Immunoregulation and Cancer: Food Design for Targeting Disease

Antioxidants ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 202 ◽  
Author(s):  
Jennifer Ahn-Jarvis ◽  
Arti Parihar ◽  
Andrea Doseff
Keyword(s):  
Immune System ◽  
Fruits And Vegetables ◽  
Dose Frequency ◽  
Biological Targets ◽  
Beneficial Effects ◽  
Agricultural Engineering ◽  
Processing Strategies ◽  
Food Design ◽  
Dietary Flavonoids

Flavonoids, one of the most abundant phytochemicals in a diet rich in fruits and vegetables, have been recognized as possessing anti-proliferative, antioxidant, anti-inflammatory, and estrogenic activities. Numerous cellular and animal-based studies show that flavonoids can function as antioxidants by preventing DNA damage and scavenging reactive oxygen radicals, inhibiting formation of DNA adducts, enhancing DNA repair, interfering with chemical damage by induction of Phase II enzymes, and modifying signaling pathways. Recent evidence also shows their ability to regulate the immune system. However, findings from clinical trials have been mixed with no clear consensus on dose, frequency, or type of flavonoids best suited to elicit many of the beneficial effects. Delivery of these bioactive compounds to their biological targets through “targeted designed” food processing strategies is critical to reach effective concentration in vivo. Thus, the identification of novel approaches that optimize flavonoid bioavailability is essential for their successful clinical application. In this review, we discuss the relevance of increasing flavonoid bioavailability, by agricultural engineering and “targeted food design” in the context of the immune system and cancer.

scholarly journals Aldosterone directly affects apelin expression and secretion in adipocytes

2013 ◽  
Vol 51 (1) ◽  
pp. 37-48 ◽  
Author(s):  
He Jiang ◽  
Xiao-Ping Ye ◽  
Zhong-Yin Yang ◽  
Ming Zhan ◽  
Hai-Ning Wang ◽  
...  
Keyword(s):  
Target Genes ◽  
Direct Interaction ◽  
Serum Levels ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Beneficial Effects ◽  
Underlying Mechanisms ◽  
Plasma Apelin ◽  
Dose Dependent

There is a high incidence of metabolic syndrome among patients with primary aldosteronism (PA), which has recently been associated with an unfavorable cardiometabolic profile. However, the underlying mechanisms have not been clarified in detail. Characterizing aldosterone (Ald) target genes in adipocytes will help us to elucidate the deleterious effects associated with excess Ald. Apelin, a novel adipokine, exerts beneficial effects on obesity-associated disorders and cardiovascular homeostasis. The objective of this study was to investigate the effects of high Ald levels on apelin expression and secretion and the underlying mechanisms involved in adipocytes. In vivo, a single-dose Ald injection acutely decreased apelin serum levels and adipose tissue apelin production, which demonstrates a clear inverse relationship between the levels of plasma Ald and plasma apelin. Experiments using 3T3-L1 adipocytes showed that Ald decreased apelin expression and secretion in a time- and dose-dependent manner. This effect was reversed by glucocorticoid receptor (GR) antagonists or GR (NR3C1) knockdown; furthermore, putative HREs were identified in the apelin promoter. Subsequently, we verified that both glucocorticoids and mineralocorticoids regulated apelin expression through GR activation, although no synergistic effect was observed. Additionally, detailed potential mechanisms involved a p38 MAPK signaling pathway. In conclusion, our findings strengthen the fact that there is a direct interaction between Ald and apelin in adipocytes, which has important implications for hyperaldosteronism or PA-associated cardiometabolic syndrome and hoists apelin on the list of potent therapeutic targets for PA.

Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence

2012 ◽  
Vol 92 (3) ◽  
pp. 407-419 ◽  
Author(s):  
Surangi H. Thilakarathna ◽  
H. P. Vasantha Rupasinghe
Keyword(s):  
Bioactive Compounds ◽  
Antioxidant Activities ◽  
Scientific Evidence ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Experimental Conditions ◽  
Beneficial Effects ◽  
Positive Effects

Thilakarathna, S. H. and Rupasinghe, H. P. V. 2012. Anti-atherosclerotic effects of fruit bioactive compounds: A review of current scientific evidence. Can. J. Plant Sci. 92: 407–419. Atherosclerosis is a condition which leads to a cascade of processes involved in thickening of arterial walls as a result of fatty deposition, which can increase the risk of cardiovascular diseases. Among numerous remedies, the consumption of fruits is believed to have beneficial effects on atherosclerosis development. Various bioactive compounds are present in fruits and they have been found to be responsible for exerting these beneficial effects. Fruit flavonoids and certain terpenoids are among the most efficacious fruit bioactive compounds that have shown positive effects on different in vitro as well as in vivo research models of atherosclerosis. The mechanisms of actions of these compounds vary from exerting antioxidant activities to anti-atherogenic and lipid lowering activities, based on different experimental models. This review article briefly explains how some of the fruit bioactive compounds have affected atherosclerosis under experimental conditions.

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