scholarly journals Phenolics-Rich Extracts of Dietary Plants as Regulators of Fructose Uptake in Caco-2 Cells via GLUT5 Involvement

Molecules ◽  
2021 ◽  
Vol 26 (16) ◽  
pp. 4745
Author(s):  
Małgorzata Zakłos-Szyda ◽  
Nina Pietrzyk ◽  
Agnieszka Kowalska-Baron ◽  
Adriana Nowak ◽  
Katarzyna Chałaśkiewicz ◽  
...  
Keyword(s):  
Mrna Level ◽  
Docking Simulation ◽  
Interacting Protein ◽  
Alcoholic Fatty Liver ◽  
Thioredoxin Interacting Protein ◽  
Protein Levels ◽  
Phenolic Constituents ◽  
Genes Encoding ◽  
Element Binding Protein ◽  
Responsive Element

The latest data link the chronic consumption of large amounts of fructose present in food with the generation of hypertension and disturbances in carbohydrate and lipid metabolism, which promote the development of obesity, non-alcoholic fatty liver disease, insulin resistance, and type 2 diabetes. This effect is possible after fructose is absorbed by the small intestine cells and, to a lesser extent, by hepatocytes. Fructose transport is dependent on proteins from the family of glucose transporters (GLUTs), among which GLUT5 selectively absorbs fructose from the intestine. In this study, we examined the effect of four phenolic-rich extracts obtained from A. graveolens, B. juncea, and M. chamomilla on fructose uptake by Caco-2 cells. Extracts from B. juncea and M. chamomilla most effectively reduced fluorescent fructose analogue (NBDF) accumulation in Caco-2, as well as downregulated GLUT5 protein levels. These preparations were able to decrease the mRNA level of genes encoding transcription factors regulating GLUT5 expression-thioredoxin-interacting protein (TXNIP) and carbohydrate-responsive element-binding protein (ChREBP). Active extracts contained large amounts of apigenin and flavonols. The molecular docking simulation suggested that some of identified phenolic constituents can play an important role in the inhibition of GLUT5-mediated fructose transport.

scholarly journals Sargahydroquinoic Acid Suppresses Hyperpigmentation by cAMP and ERK1/2-Mediated Downregulation of MITF in α-MSH-Stimulated B16F10 Cells

Foods ◽  
2021 ◽  
Vol 10 (10) ◽  
pp. 2254
Author(s):  
Mohammed Shariful Azam ◽  
Bonggi Lee ◽  
Jae-Il Kim ◽  
Chang Geun Choi ◽  
Jinkyung Choi ◽  
...  
Keyword(s):  
Docking Simulation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Regulatory Subunit ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Creb Activation ◽  
B16f10 Cells ◽  
Element Binding Protein ◽  
Responsive Element

Hyperpigmentation diseases of the skin require topical treatment with depigmenting agents. We investigated the hypopigmented mechanisms of sargahydroquinoic acid (SHQA) in alpha-melanocyte-stimulating hormone (α-MSH)-stimulated B16F10 cells. SHQA reduced cellular tyrosinase (TYR) activity and melanin content in a concentration-dependent manner and attenuated the expression of TYR and tyrosinase-related protein 1 (TRP1), along with their transcriptional regulator, microphthalmia-associated transcription factor (MITF). SHQA also suppressed α-MSH-induced cellular production of cyclic adenosine monophosphate (cAMP), which inhibited protein kinase A (PKA)-dependent cAMP-responsive element-binding protein (CREB) activation. Docking simulation data showed a potential binding affinity of SHQA to the regulatory subunit RIIβ of PKA, which may also adversely affect PKA and CREB activation. Moreover, SHQA activated ERK1/2 signaling in B16F10 cells, stimulating the proteasomal degradation of MITF. These data suggest that SHQA ameliorated hyperpigmentation in α-MSH-stimulated B16F10 cells by downregulating MITF via PKA inactivation and ERK1/2 phosphorylation, indicating that SHQA is a potent therapeutic agent against skin hyperpigmentation disorders.

Molecular mechanisms underlying K+ current downregulation in canine tachycardia-induced heart failure

2005 ◽  
Vol 288 (6) ◽  
pp. H2887-H2896 ◽  
Author(s):  
Fadi G. Akar ◽  
Richard C. Wu ◽  
George J. Juang ◽  
Yanli Tian ◽  
Mirka Burysek ◽  
...  
Keyword(s):  
Heart Failure ◽  
Molecular Mechanisms ◽  
Canine Model ◽  
Delayed Rectifier ◽  
Interacting Protein ◽  
Altered Expression ◽  
Protein Levels ◽  
Delayed Rectifier Current ◽  
Repolarization Reserve ◽  
Genes Encoding

Heart failure (HF) is characterized by marked prolongation of action potential duration and reduction in cellular repolarization reserve. These changes are caused in large part by HF-induced K+ current downregulation. Molecular mechanisms underlying these changes remain unclear. We determined whether downregulation of K+ currents in a canine model of tachycardia-induced HF is caused by altered expression of underlying K+ channel α- and β-subunits encoding these currents. K+ channel subunit expression was quantified in normal and failing dogs at the mRNA and protein levels in epicardial (Epi), midmyocardial (Mid), and endocardial (Endo) layers of left ventricle. Analysis of mRNA and protein levels of candidate genes encoding the transient outward K+ current ( Ito) revealed marked reductions in canine cKv4.3 expression in HF in Epi (44% mRNA, 39% protein), Mid (52% mRNA, 34% protein), and Endo (49% mRNA, 73% protein) layers and a paradoxical enhancement (41% Epi, 97% Mid, 113% Endo) in cKv1.4 protein levels, without significant changes in Kv channel-interacting protein cKChIP2 expression. Expression of cKir2.1, the gene underlying inward rectifier K+ current ( IK1), was unaffected by HF at mRNA and protein levels despite significant reduction in IK1, whereas canine ether-à-go-go-related gene (cERG), which encodes the rapidly activating component of the delayed rectifier current ( IK), exhibited increased protein expression. HF was not accompanied by significant changes in cKvLQT1 or cMinK mRNA and protein levels. These data indicate that 1) downregulation of Ito in HF is associated with decreased cKv4.3 and not cKv1.4 or cKChIP2, and 2) alterations in both the rapidly activating and slowly activating components of IK as well as IK1 in nonischemic dilated cardiomyopathy are not caused by changes in either transcript or immunoreactive protein levels of relevant channel subunits, which suggests posttranslational modification of these currents by HF.

Inhibition of MITF and Tyrosinase by Paeonol-Stimulated JNK/SAPK to Reduction of Phosphorylated CREB

2008 ◽  
Vol 36 (02) ◽  
pp. 245-263 ◽  
Author(s):  
Jin Bu ◽  
Peng-Cheng Ma ◽  
Zhi-Qiang Chen ◽  
Wu-Qing Zhou ◽  
You-Jun Fu ◽  
...  
Keyword(s):  
Down Regulation ◽  
Creb Phosphorylation ◽  
Protein Levels ◽  
B16f10 Cells ◽  
Element Binding Protein ◽  
Extracellular Stimuli ◽  
Responsive Element ◽  
Phosphorylated Creb ◽  
Pka Pathway ◽  
Mitf Expression

Tyrosinase and its transcriptional regulator microphthalmia-associated transcription factor (MITF) play critical roles in regulation of melanogenesis, and are required for environmental cues or agents in modulation of melanin synthesis. Identifying the signals regulating tyrosinase and MITF is crucial to understanding how pigmentation responds to extracellular stimuli. In this report, we discovered that paeonol down-regulated melanin production via decreasing MITF expression and consequent mRNA and protein levels of tyrosinase. We also found that paeonol reduced phosphorylation of a cAMP responsive element binding protein (phospho-CREB), which binds and activates MITF. A selective inhibitor of c-jun N-terminal or stress-activated protein kinases (JNK/SAPK)-SP600125 significantly reversed paeonol-induced down-regulation of melanogenesis. Inhibition of cAMP/PKA pathway intensified the hypopigmentation response to paeonol. These results identify a mechanism in which paeonol induces the down-regulation of melanogenesis through inhibition of CREB phosphorylation, leading to the expression reduction of MITF and subsequently tyrosinase. The key kinase mediating the effects of paeonol on melanogenesis in B16F10 cells is JNK/SAPK. Additionally, the cAMP/PKA pathway may take part in this process.

scholarly journals Luteolin 7-Sulfate Attenuates Melanin Synthesis through Inhibition of CREB- and MITF-Mediated Tyrosinase Expression

Antioxidants ◽  
2019 ◽  
Vol 8 (4) ◽  
pp. 87 ◽  
Author(s):  
Seok Lee ◽  
Jae Kim ◽  
Hyerim Song ◽  
Jin Seok ◽  
Seong Hong ◽  
...  
Keyword(s):  
Melanin Synthesis ◽  
Protein Levels ◽  
Melanocyte Stimulating Hormone ◽  
Toxic Concentration ◽  
Element Binding Protein ◽  
Responsive Element ◽  
Tyrosinase Expression ◽  
Phyllospadix Iwatensis ◽  
Tyr Gene ◽  
Camp Responsive Element Binding

Antioxidants with antimelanogenic activity are potentially useful for the attenuation of skin hyperpigmentation disorders. In a previous study, luteolin 7-sulfate isolated from Phyllospadix iwatensis Makino, a marine plant, was shown to inhibit cellular melanin synthesis. The aim of the present study was to examine its action mechanism, focusing on the regulation of tyrosinase (TYR) expression in cells. Cell-based assay was undertaken using murine melanoma B16-F10 cells and primary human epidermal melanocytes (HEMs). Luteolin 7-sulfate showed lower toxicity compared to luteolin in B16-F10 cells. At the non-toxic concentration ranges, luteolin 7-sulfate attenuated melanin synthesis, stimulated by α-melanocyte-stimulating hormone or forskolin. Luteolin 7-sulfate attenuated forskolin-induced microphthalmia-associated transcription factor (MITF) and TYR expressions at the mRNA and protein levels in B16-F10 cells. It also attenuated the phosphorylation of cAMP-responsive element binding protein (CREB) stimulated by forskolin. Luteolin 7-sulfate also attenuated melanin synthesis in primary HEMs. This study demonstrates that luteolin 7-sulfate attenuates TYR gene expression through the intervention of a CREB- and MITF-mediated signaling pathway, leading to the decreased melanin synthesis.

scholarly journals Posttranslational regulation of thioredoxin-interacting protein

2012 ◽  
Vol 50 (1) ◽  
pp. 59-71 ◽  
Author(s):  
Katherine A Robinson ◽  
Jonathan W Brock ◽  
Maria G Buse
Keyword(s):  
Kinase Inhibitor ◽  
Pi3 Kinase ◽  
Interacting Protein ◽  
Hek 293 ◽  
Ubiquitin Proteasome Pathway ◽  
Thioredoxin Interacting Protein ◽  
Protein Levels ◽  
L6 Myotubes ◽  
Ubiquitin Proteasome ◽  
Proteasome Pathway

Thioredoxin-interacting protein (Txnip) is a metabolic regulator, which modulates insulin sensitivity and likely plays a role in type 2 diabetes. We studied the regulation of Txnip in 3T3-L1 adipocytes. Cells were incubated under different conditions and Txnip was measured by immunoblotting. We confirmed that high glucose markedly increases Txnip expression by promoting transcription. Insulin decreases Txnip protein levels. Rapamycin under most conditions decreased Txnip, suggesting that mTOR complex-1 is involved. The acute effects of insulin are mainly posttranscriptional; insulin (100 nM) accelerates Txnip degradation more than tenfold. This effect is cell type specific. It works in adipocytes, preadipocytes and in L6 myotubes but not in HepG2 or in HEK 293 cells or in a pancreatic β-cell line. The ubiquitin/proteasome pathway is involved. Degradation of Txnip occurred within 15 min in the presence of 3 nM insulin and overnight with 0.6 nM insulin. Proteasomal Txnip degradation is not mediated by a cysteine protease or an anti-calpain enzyme. Okadaic acid (OKA), an inhibitor of phosphoprotein phosphatases (pp), markedly reduced Txnip protein and stimulated its further decrease by insulin. The latter occurred after incubation with 1 or 1000 nM OKA, suggesting that insulin enhances the phosphorylation of a pp2A substrate. Incubation with 0.1 μM Wortmannin, a PI3 kinase inhibitor, increased Txnip protein twofold and significantly inhibited its insulin-induced decrease. Thus, while OKA mimics the effect of insulin, Wortmannin opposes it. In summary, insulin stimulates Txnip degradation by a PI3 kinase-dependent mechanism, which activates the ubiquitin/proteasome pathway and likely serves to mitigate insulin resistance.

Functional amyloid: widespread in Nature, diverse in purpose

2014 ◽  
Vol 56 ◽  
pp. 207-219 ◽  
Author(s):  
Chi L.L. Pham ◽  
Ann H. Kwan ◽  
Margaret Sunde
Keyword(s):  
Spider Silk ◽  
Epigenetic Inheritance ◽  
Fibrillar Structure ◽  
Cytoplasmic Polyadenylation ◽  
Functional Amyloid ◽  
Interacting Protein ◽  
Diverse Range ◽  
Element Binding Protein ◽  
Functional Amyloids ◽  
Micro Organisms

Amyloids are insoluble fibrillar protein deposits with an underlying cross-β structure initially discovered in the context of human diseases. However, it is now clear that the same fibrillar structure is used by many organisms, from bacteria to humans, in order to achieve a diverse range of biological functions. These functions include structure and protection (e.g. curli and chorion proteins, and insect and spider silk proteins), aiding interface transitions and cell–cell recognition (e.g. chaplins, rodlins and hydrophobins), protein control and storage (e.g. Microcin E492, modulins and PMEL), and epigenetic inheritance and memory [e.g. Sup35, Ure2p, HET-s and CPEB (cytoplasmic polyadenylation element-binding protein)]. As more examples of functional amyloid come to light, the list of roles associated with functional amyloids has continued to expand. More recently, amyloids have also been implicated in signal transduction [e.g. RIP1/RIP3 (receptor-interacting protein)] and perhaps in host defence [e.g. aDrs (anionic dermaseptin) peptide]. The present chapter discusses in detail functional amyloids that are used in Nature by micro-organisms, non-mammalian animals and mammals, including the biological roles that they play, their molecular composition and how they assemble, as well as the coping strategies that organisms have evolved to avoid the potential toxicity of functional amyloid.

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