scholarly journals Anti-Photoaging and Anti-Melanogenesis Effects of Fucoidan Isolated from Hizikia fusiforme and Its Underlying Mechanisms

Marine Drugs ◽  
2020 ◽  
Vol 18 (8) ◽  
pp. 427 ◽  
Author(s):  
Lei Wang ◽  
Jae-Young Oh ◽  
Young-Sang Kim ◽  
Hyo-Geun Lee ◽  
Jung-Suck Lee ◽  
...  
Keyword(s):  
Human Keratinocytes ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Concentration Dependent Manner ◽  
B16f10 Cells ◽  
Hizikia Fusiforme ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms ◽  
Induced Apoptosis

Previous studies suggested that fucoidan with a molecular weight of 102.67 kDa, isolated from Hizikia fusiforme, possesses strong antioxidant activity. To explore the cosmeceutical potential of fucoidan, its anti-photoaging and anti-melanogenesis effects were evaluated in the present study. The anti-photoaging effect was investigated in ultraviolet (UV) B-irradiated human keratinocytes (HaCaT cells), where fucoidan effectively reduced the intracellular reactive oxygen species level and improved the viability of the UVB-irradiated cells without any cytotoxic effects. Moreover, fucoidan significantly decreased UVB-induced apoptosis in HaCaT cells by regulating the protein expression of Bax, Bcl-xL, PARP, and Caspase-3 in HaCaT cells in a concentration-dependent manner. The anti-melanogenesis effect of fucoidan was evaluated in B16F10 melanoma cells that had been stimulated with alpha-melanocyte-stimulating hormone (α-MSH), and fucoidan treatment remarkably inhibited melanin synthesis in α-MSH-stimulated B16F10 cells. Further studies indicated that fucoidan significantly suppressed the expression of tyrosinase and tyrosinase-related protein-1 and -2 (TRP-1 and-2) in B16F10 cells by down-regulating microphthalmia-associated transcription factor (MITF) through regulation of the ERK–MAPK (extracellular signal regulated kinase-mitogen activated protein kinase) pathway. Taken together, these results suggest that fucoidan isolated from H. fusiforme possesses strong anti-photoaging and anti-melanogenesis activities and can be used as an ingredient in the pharmaceutical and cosmeceutical industries.

scholarly journals UVB-mediated activation of p38 mitogen-activated protein kinase enhances resistance of normal human keratinocytes to apoptosis by stabilizing cytoplasmic p53

2002 ◽  
Vol 365 (1) ◽  
pp. 133-145 ◽  
Author(s):  
Nadine CHOUINARD ◽  
Kristoffer VALERIE ◽  
Mahmoud ROUABHIA ◽  
Jacques HUOT
Keyword(s):  
Adaptive Response ◽  
Human Keratinocytes ◽  
Dominant Negative ◽  
Mitogen Activated Protein Kinase ◽  
Dominant Negative Mutant ◽  
Normal Human Keratinocytes ◽  
Mitogen Activated Protein ◽  
Normal Human ◽  
Induced Apoptosis ◽  
Negative Mutant

Human keratinocytes respond to UV rays by developing a fast adaptive response that contributes to maintaining their functions and survival. We investigated the role of the mitogen-activated protein kinase pathways in transducing the UV signals in normal human keratinocytes. We found that UVA, UVB or UVC induced a marked and persistent activation of p38, whereas c-Jun N-terminal kinase or extracellular signal-regulated kinase were less or not activated respectively. Inhibition of p38 activity by expression of a dominant-negative mutant of p38 or with SB203580 impaired cell viability and led to an increase in UVB-induced apoptosis. This sensitization to apoptosis was independent of caspase activities. Inhibition of p38 did not sensitize transformed HaCaT keratinocytes to UVB-induced apoptosis. In normal keratinocytes, expression of a dominant-negative mutant of p53 increased UVB-induced cell death, pointing to a role for p53. In these cells, UVB triggered a p38-dependent phosphorylation of p53 on Ser-15. This phosphorylation was associated with an SB203580-sensitive accumulation of p53, even in the presence of a serine phosphatase inhibitor. Accumulated p53 was localized mainly in the cytoplasm, independently of CRM1 nuclear export. In HaCaT cells, p53 was localized exclusively in the nucleus and its distribution and level were not affected by UVB or p38 inhibition. However, UVB induced an SB203580-insensitive phosphorylation on Ser-15 of mutated p53. Overall, our results suggest that, in normal human keratinocytes, protection against UVB depends on p38-mediated phosphorylation and stabilization of p53 and is tightly associated with the cytoplasmic sequestration of wild-type p53. We conclude that the p38/p53 pathway plays a key role in the adaptive response of normal human keratinocytes against UV stress.

scholarly journals Metformin Alleviated Aβ-Induced Apoptosis via the Suppression of JNK MAPK Signaling Pathway in Cultured Hippocampal Neurons

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Bin Chen ◽  
Ying Teng ◽  
Xingguang Zhang ◽  
Xiaofeng Lv ◽  
Yanling Yin
Keyword(s):  
P38 Mapk ◽  
Hippocampal Neurons ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ldh Assay ◽  
Underlying Mechanisms ◽  
Induced Apoptosis ◽  
Positive Effect

Both diabetes and hyperinsulinemia are confirmed risk factors for Alzheimer’s disease. Some researchers proposed that antidiabetic drugs may be used as disease-modifying therapies, such as metformin and thiazolidinediones, although more evidence was poorly supported. The aim of the current study is to investigate the role of metformin in Aβ-induced cytotoxicity and explore the underlying mechanisms. First, the experimental results show that metformin salvaged the neurons exposed to Aβin a concentration-dependent manner with MTT and LDH assay. Further, the phosphorylation levels of JNK, ERK1/2, and p38 MAPK were measured with western blot analysis. It was investigated that Aβincreased phospho-JNK significantly but had no effect on phospho-p38 MAPK and phospho-ERK1/2. Metformin decreased hyperphosphorylated JNK induced by Aβ; however, the protection of metformin against Aβwas blocked when anisomycin, the activator of JNK, was added to the medium, indicating that metformin performed its protection against Aβin a JNK-dependent way. In addition, it was observed that metformin protected the neurons via the suppression of apoptosis. Taken together, our findings demonstrate that metformin may have a positive effect on Aβ-induced cytotoxicity, which provides a preclinical strategy against AD for elders with diabetes.

scholarly journals Collagen/β1 integrin signaling up-regulates the ABCC1/MRP-1 transporter in an ERK/MAPK-dependent manner

2012 ◽  
Vol 23 (17) ◽  
pp. 3473-3484 ◽  
Author(s):  
Mohammed-Amine El Azreq ◽  
Dalila Naci ◽  
Fawzi Aoudjit
Keyword(s):  
Actin Polymerization ◽  
Mitogen Activated Protein Kinase ◽  
Integrin Signaling ◽  
Β1 Integrin ◽  
Dependent Manner ◽  
Expression Levels ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Induced Apoptosis ◽  
And Function

The mechanisms by which β1 integrins regulate chemoresistance of cancer cells are still poorly understood. In this study, we report that collagen/β1 integrin signaling inhibits doxorubicin-induced apoptosis of Jurkat and HSB2 leukemic T-cells by up-regulating the expression and function of the ATP-binding cassette C 1 (ABCC1) transporter, also known as multidrug resistance–associated protein 1. We find that collagen but not fibronectin reduces intracellular doxorubicin content and up-regulates the expression levels of ABCC1. Inhibition and knockdown studies show that up-regulation of ABCC1 is necessary for collagen-mediated reduction of intracellular doxorubicin content and collagen-mediated inhibition of doxorubicin-induced apoptosis. We also demonstrate that activation of the extracellular signal-regulated kinase (ERK)/mitogen-activated protein kinase signaling pathway is involved in collagen-induced reduction of intracellular doxorubicin accumulation, collagen-induced up-regulation of ABCC1 expression levels, and collagen-mediated cell survival. Finally, collagen-mediated up-regulation of ABCC1 expression and function also requires actin polymerization. Taken together, our results indicate for the first time that collagen/β1 integrin/ERK signaling up-regulates the expression and function of ABCC1 and suggest that its activation could represent an important pathway in cancer chemoresistance. Thus simultaneous targeting of collagen/β1 integrin and ABCC1 may be more efficient in preventing drug resistance than targeting each pathway alone.

scholarly journals Oxidative Stress and Mitogen-Activated Protein Kinase Pathways Involved in Cadmium-Induced BRL 3A Cell Apoptosis

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Zhang Yiran ◽  
Jiang Chenyang ◽  
Wang Jiajing ◽  
Yuan Yan ◽  
Gu Jianhong ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Mrna Levels ◽  
Dependent Manner ◽  
Nuclear Condensation ◽  
Concentration Dependent Manner ◽  
P38 Inhibitor ◽  
Mapk Pathways ◽  
Induced Apoptosis

In this study, BRL 3A cells were treated with different Cd concentrations (0, 10, 20, and 40 μmol/L) for 12 h and preincubated with or without N-acetyl-L-cysteine (NAC) (2 mmol/L) for 30 min, and cells were treated with Cd (0 and 20 μmol/L), pretreated with p38 inhibitor (SB203580), JNK (c-Jun NH2-terminal kinases) inhibitor (SP600125), and extracellular signal-regulated kinase (ERK) inhibitor (U0126) for 30 min, and then treated with 20 μmol/L Cd for 12 h. Cd decreased cell viability, SOD, and GSH-Px activity in a concentration-dependent manner. Increased MDA level, ROS generation, nuclear condensation, shrinkage, and fragmentation in cell morphology were inhibited by NAC. Cd-induced apoptosis was attenuated by pretreatment with SB203580, SP600125, and U0126. The results of western blot showed that NAC preincubation affected Cd-activated MAPK pathways, p38 and ERK phosphorylation. Cd treatment elevated the mRNA levels of Bax and decreased the mRNA levels of Bcl-2, respectively. The same effect was found in their protein expression levels. These results suggest that oxidative stress and MAPK pathways participate in Cd-induced apoptosis and that the balance between pro- and antiapoptotic genes (Bax and Bcl-2) is important in Cd-induced apoptosis.

scholarly journals Chrysoeriol Enhances Melanogenesis in B16F10 Cells Through the Modulation of the MAPK, AKT, PKA, and Wnt/β-Catenin Signaling Pathways

2022 ◽  
Vol 17 (1) ◽  
pp. 1934578X2110692
Author(s):  
So-Yeon Oh ◽  
Chang-Gu Hyun
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Transcriptional Activation ◽  
Glycogen Synthase ◽  
Multidrug Resistant ◽  
Antimicrobial Activities ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
B16f10 Cells

Chrysoeriol is a 3′-O-methoxy flavone, chemically a derivative of luteolin, which is commonly found across the plant kingdom. Chrysoeriol is of great scientific interest because of its promising anti-inflammatory, anti-cancer, antioxidative, anti-lipase, anti-xanthin oxidase, and antimicrobial activities against multidrug-resistant (MDR) bacterial pathogens; however, its effects on melanogenesis have not yet been elucidated. Here, we report a novel effect of chrysoeriol on melanogenesis in B16F10 cells. Chrysoeriol treatment significantly increased the expression of the melanogenic enzymes tyrosinase (TRY), tyrosinase-related protein-1 (TRP-1), and TRP-2 and upregulated the expression of microphthalmia-associated transcription factor (MITF) in a concentration-dependent manner. Furthermore, chrysoeriol suppressed the phosphorylation of extracellular signal-regulated kinase (ERK) and protein kinase B (AKT) in a concentration-dependent manner. In addition, chrysoeriol treatment increased the phosphorylation of p38 mitogen-activated protein kinase (MAPK), glycogen synthase kinase (GSK)-3β, β-catenin, and protein kinase A (PKA) and decreased the production of β-catenin, which is involved in the transcriptional activation of MITF in melanogenesis. Finally, the structure–activity relationship (SAR) of chrysoeriol and its derivatives, including luteolin and apigenin, with regard to their melanin inhibitory activity was also investigated; we identified the significance of the 4′-OH group and C-3′ methoxylation in melanogenesis. Together, these findings indicate that chrysoeriol promotes melanogenesis in B16F10 cells by upregulating the expression of melanogenic enzymes through the MAPK, phosphatidylinositol 3-kinase (PI3K)/AKT, PKA, and Wnt/β-catenin signaling pathways; thus, chrysoeriol may be used as a cosmetic ingredient to promote melanogenesis or as a therapeutic agent against hypopigmentation disorders.

scholarly journals Effects of Wannachawee Recipe with Antipsoriatic Activity on Suppressing Inflammatory Cytokine Production in HaCaT Human Keratinocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-12 ◽  
Author(s):  
Mingkwan Na Takuathung ◽  
Ariyaphong Wongnoppavich ◽  
Pornsiri Pitchakarn ◽  
Ampai Panthong ◽  
Parirat Khonsung ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Cell Cycle Progression ◽  
Human Keratinocytes ◽  
Convincing Evidence ◽  
Potential Candidate ◽  
Dependent Manner ◽  
Hacat Cells ◽  
Concentration Dependent Manner ◽  
Folk Remedy ◽  
Anti Inflammatory

Psoriasis is a chronic inflammatory and immune-mediated skin disease. The pathogenesis involves T cells activation via the IL-23/Th17 axis. Conventional treatments of psoriasis have adverse events influencing patients’ adherence. Wannachawee Recipe (WCR) has been effectively used as Thai folk remedy for psoriasis patients; however, preclinical evidence defining how WCR works is still lacking. This study defined mechanisms for its antiproliferation and anti-inflammatory effects in HaCaT cells. The cytotoxicity and antiproliferation results from SRB and CCK-8 assays showed that WCR inhibited the growth and viability of HaCaT cells in a concentration-dependent manner. The distribution of cell cycle phases determined by flow cytometry showed that WCR did not interrupt cell cycle progression. Interestingly, RT-qPCR revealed that WCR significantly decreased the mRNA expression of IL-1β, IL-6, IL-8, IL-17A, IL-22, IL-23, and TNF-α but induced IL-10 expression in TNF-α- and IFN-γ-induced HaCaT cells. At the protein level determined by ELISA, WCR significantly reduced the secretion of IL-17A, IL-22, and IL-23. The WCR at low concentrations was proved to possess anti-inflammatory effect without cytotoxicity and it did not interfere with cell cycle of keratinocytes. This is the first study to provide convincing evidence that WCR is a potential candidate for development of effective psoriasis therapies.

scholarly journals New Benzimidazothiazolone Derivatives as Tyrosinase Inhibitors with Potential Anti-Melanogenesis and Reactive Oxygen Species Scavenging Activities

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1078
Author(s):  
Hee Jin Jung ◽  
Dong Chan Choi ◽  
Sang Gyun Noh ◽  
Heejeong Choi ◽  
Inkyu Choi ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Inhibitory Activity ◽  
Camp Response Element Binding ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Docking Simulations ◽  
B16f10 Cells ◽  
Tyrosinase Inhibitors

Thirteen (Z)-2-(substituted benzylidene)benzimidazothiazolone analogs were synthesized and evaluated for their inhibitory activity against mushroom tyrosinase. Among the compounds synthesized, compounds 1–3 showed greater inhibitory activity than kojic acid (IC50 = 18.27 ± 0.89 μM); IC50 = 3.70 ± 0.51 μM for 1; IC50 = 3.05 ± 0.95 μM for 2; and IC50 = 5.00 ± 0.38 μM for 3, and found to be competitive tyrosinase inhibitors. In silico molecular docking simulations demonstrated that compounds 1–3 could bind to the catalytic sites of tyrosinase. Compounds 1–3 inhibited melanin production and cellular tyrosinase activity in a concentration-dependent manner. Notably, compound 2 dose-dependently scavenged ROS in B16F10 cells. Furthermore, compound 2 downregulated the protein kinase A (PKA)/cAMP response element-binding protein (CREB) and mitogen-activated protein kinase (MAPK) signaling pathways, which led to a reduction in microphthalmia-associated transcription factor (MITF) expression, and decreased tyrosinase, tyrosinase related protein 1 (TRP1), and TRP2 expression, resulting in anti-melanogenesis activity. Hence, compound 2 may serve as an anti-melanogenic agent against hyperpigmentation diseases.

α1-Adrenergic and cholinergic agonists activate MAPK by separate mechanisms to inhibit secretion in lacrimal gland

2003 ◽  
Vol 284 (1) ◽  
pp. C168-C178 ◽  
Author(s):  
Isao Ota ◽  
Driss Zoukhri ◽  
Robin R. Hodges ◽  
José D. Rios ◽  
Vanja Tepavcevic ◽  
...  
Keyword(s):  
Protein Secretion ◽  
Lacrimal Gland ◽  
Egf Receptor ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Signaling Mechanisms ◽  
Mitogen Activated Protein ◽  
Secretion Inhibition

The purpose of this study was to determine the role of p42/p44 mitogen-activated protein kinase (MAPK) in α1-adrenergically and cholinergically stimulated protein secretion in rat lacrimal gland acinar cells and the pathways used by these agonists to activate MAPK. Acini were isolated by collagenase digestion and incubated with the α1-adrenergic agonist phenylephrine or the cholinergic agonist carbachol, and activation of MAPK and protein secretion were then measured. Phenylephrine and carbachol activated MAPK in a time- and concentration-dependent manner. Inhibition of MAPK significantly increased phenylephrine- and carbachol-induced protein secretion. Inhibition of EGF receptor (EGFR) with AG1478, an inhibitor of the EGFR tyrosine kinase activity, significantly increased phenylephrine- but not carbachol-induced protein secretion. Whereas phenylephrine-induced activation of MAPK was completely inhibited by AG1478, activation of MAPK by carbachol was not. Phenylephrine stimulated tyrosine phosphorylation of the EGFR, whereas carbachol stimulated p60Src, and possibly Pyk2, to activate MAPK. We conclude that, in the lacrimal gland, activation of MAPK plays an inhibitory role in α1-adrenergically and cholinergically stimulated protein secretion and that these agonists use different signaling mechanisms to activate MAPK.

Sign in / Sign up

Export Citation Format

Share Document