scholarly journals In VitroManganese Exposure Disrupts MAPK Signaling Pathways in Striatal and Hippocampal Slices from Immature Rats

2013 ◽  
Vol 2013 ◽  
pp. 1-12 ◽  
Author(s):  
Tanara Vieira Peres ◽  
Daniela Zótico Pedro ◽  
Fabiano Mendes de Cordova ◽  
Mark William Lopes ◽  
Filipe Marques Gonçalves ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Hippocampal Slices ◽  
Total Content ◽  
Brain Structures ◽  
Mapk Signaling ◽  
Early Event ◽  
Striatal Slices ◽  
Immature Rats

The molecular mechanisms mediating manganese (Mn)-induced neurotoxicity, particularly in the immature central nervous system, have yet to be completely understood. In this study, we investigated whether mitogen-activated protein kinases (MAPKs) and tyrosine hydroxylase (TH) could represent potential targets of Mn in striatal and hippocampal slices obtained from immature rats (14 days old). The aim of this study was to evaluate if the MAPK pathways are modulated after subtoxic Mn exposure, which do not significantly affect cell viability. The concentrations of manganese chloride (MnCl2; 10–1,000 μM) caused no change in cell viability in slices exposed for 3 or 6 hours. However, Mn exposure significantly increased extracellular signal-regulated kinase (ERK) 1/2, as well as c-Jun N-terminal kinase (JNK) 1/2/3 phosphorylation at both 3 and 6 hours incubations, in both brain structures. Furthermore, Mn exposure did not change the total content or phosphorylation of TH at the serine 40 site in striatal slices. Thus, Mn at concentrations that do not disrupt cell viability causes activation of MAPKs (ERK1/2 and JNK1/2/3) in immature hippocampal and striatal slices. These findings suggest that altered intracellular MAPKs signaling pathways may represent an early event concerning the effects of Mn in the immature brain.

scholarly journals The effects of 50 Hz magnetic field–exposed cell culture medium on cellular functions in FL cells

2019 ◽  
Vol 60 (4) ◽  
pp. 424-431 ◽  
Author(s):  
Yue Fei ◽  
Liling Su ◽  
Haifeng Lou ◽  
Chuning Zhao ◽  
Yiqin Wang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Signaling Pathways ◽  
Relative Permittivity ◽  
Culture Medium ◽  
Biological Effects ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Cell Counting ◽  
International Agency ◽  
Dependent Manner

Abstract Although extremely low frequency magnetic fields (ELF-MFs) have been classified as a possible carcinogen for humans by the International Agency for Research on Cancer (IARC), their biological effects and underlying mechanisms are still unclear. Our previous study indicated that ELF-MF exposure influenced the relative permittivity of the saline solution, suggesting that the MF exposure altered physical properties of the solution. To explore the biophysical mechanism of ELF-MF–induced biological effects, this study examined the effects of 50 Hz sinusoidal MF at 0–4.0 mT on the permittivity of culture medium with phase-interrogation surface plasmon resonance (SPR) sensing. Then, the biological effects of MF pre-exposed culture medium on cell viability, the mitogen-activated protein kinase (MAPK) signaling pathways, oxidative stress, and genetic stabilities were analyzed using Cell Counting Kit-8, western blot, flow cytometry, γH2AX foci formation, and comet assay. The results showed that SPR signals were decreased under MF exposure in a time- and dose-dependent manner, and the decreased SPR signals were reversible when the exposure was drawn off. However, MF pre-exposed culture medium did not significantly change cell viability, intracellular reactive oxygen species level, activation of the MARK signaling pathways, or genetic stabilities in human amniotic epithelial cells (FL cells). In conclusion, our data suggest that the relative permittivity of culture medium was influenced by 50 Hz MF exposure, but this change did not affect the biological processes in FL cells.

Berberine inhibits lipopolysaccharide-induced expression of inflammatory cytokines by suppressing TLR4-mediated NF-ĸB and MAPK signaling pathways in rumen epithelial cells of Holstein calves

2019 ◽  
Vol 86 (2) ◽  
pp. 171-176 ◽  
Author(s):  
Chenxu Zhao ◽  
Yazhou Wang ◽  
Xue Yuan ◽  
Guoquan Sun ◽  
Bingyu Shen ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Signaling Pathways ◽  
Inflammatory Cytokines ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Inflammatory Drug ◽  
Anti Inflammatory ◽  
Mapk Signaling Pathways ◽  
Rumen Epithelial Cells

AbstractSubacute ruminal acidosis (SARA) can increase the level of inflammation and induce rumenitis in dairy cows. Berberine (BBR) is the major active component of Rhizoma Coptidis, which is a type of Chinese anti-inflammatory drug for gastrointestinal diseases. The purpose of this study was to investigate the anti-inflammatory effects of BBR on lipopolysaccharide (LPS)-stimulated rumen epithelial cells (REC) and the underlying molecular mechanisms. REC were cultured and stimulated with LPS in the presence or absence of different concentrations of BBR. The results showed that cell viability was not affected by BBR. Moreover, BBR markedly decreased the concentrations and mRNA expression of pro-inflammatory cytokines, including tumor necrosis factor-α, interleukin-1β, and interleukin-6 in the LPS-treated REC in a dose-dependent manner. Importantly, Western blotting analysis showed that BBR significantly suppressed the protein expression of toll-like receptor 4 (TLR4) and myeloid differentiation primary response protein (MyD88) and the phosphorylation of nuclear factor-κB (NF-κB), inhibitory kappa B (IκBα), p38 mitogen-activated protein kinase (MAPK), and c-Jun N-terminal kinase (JNK) in LPS-treated REC. Furthermore, the results of immunocytofluorescence showed that BBR significantly inhibited the nuclear translocation of NF-κB p65 induced by LPS treatment. In conclusion, the protective effects of BBR on LPS-induced inflammatory responses in REC may be due to its ability to suppress the TLR4-mediated NF-κB and MAPK signaling pathways. These findings suggest that BBR can be used as an anti-inflammatory drug to treat inflammation induced by SARA.

scholarly journals Hydrangea serrata (Thunb.) Ser. Extract Attenuate UVB-Induced Photoaging through MAPK/AP-1 Inactivation in Human Skin Fibroblasts and Hairless Mice

Nutrients ◽  
2019 ◽  
Vol 11 (3) ◽  
pp. 533 ◽  
Author(s):  
Hee-Soo Han ◽  
Ji-Sun Shin ◽  
Da-Bin Myung ◽  
Hye Ahn ◽  
Sun Lee ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Collagen Degradation ◽  
Hot Water ◽  
Mrna Levels ◽  
Skin Damage ◽  
Hairless Mice ◽  
Skin Photoaging ◽  
Mapk Signaling Pathways

Skin photoaging is mainly caused by exposure to ultraviolet (UV) light, which increases expressions of matrix metalloproteinases (MMPs) and destroys collagen fibers, consequently inducing wrinkle formation. Nutritional factors have received scientific attention for use as agents for normal skin functions. The aim of this study was to investigate the effect of hot water extracts from the leaves of Hydrangea serrata (Thunb.) Ser. (WHS) against ultraviolet B (UVB)-induced skin photoaging and to elucidate the underlying molecular mechanisms in human foreskin fibroblasts (Hs68) and HR-1 hairless mice. WHS recovered UVB-reduced cell viability and ameliorated oxidative stress by inhibiting intracellular reactive oxygen species (ROS) generation in Hs68 cells. WHS rescued UVB-induced collagen degradation by suppressing MMP expression, and reduced the mRNA levels of inflammatory cytokines. These anti-photoaging activities of WHS were associated with inhibition of the activator protein 1 (AP-1), signal transduction and activation of transcription 1 (STAT1), and mitogen-activated protein kinase (MAPK) signaling pathways. Oral administration of WHS effectively alleviated dorsal skin from wrinkle formation, epidermal thickening, collagen degradation, and skin dehydration in HR-1 hairless mice exposed to UVB. Notably, WHS suppressed UVB activation of the AP-1 and MAPK signaling pathways in dorsal mouse skin tissues. Taken together, our data indicate that WHS prevents UVB-induced skin damage due to collagen degradation and MMP activation via inactivation of MAPK/AP-1 signaling pathway.

scholarly journals Compound Dihuang Granule Inhibits Nigrostriatal Pathway Apoptosis in Parkinson’s Disease by Suppressing the JNK/AP-1 Pathway

2021 ◽  
Vol 12 ◽  
Author(s):  
Li Wang ◽  
Yu-fang Yang ◽  
Long Chen ◽  
Zhu-qing He ◽  
Dian-yong Bi ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Signaling Pathways ◽  
Experimental Validation ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Mapk Signaling ◽  
Network Pharmacology ◽  
Nigrostriatal Pathway ◽  
Bax Protein

Compound Dihuang Granule (CDG) is widely used in traditional Chinese medicine (TCM) for the treatment of Parkinson’s disease (PD). It has been shown to alleviate PD symptoms. However, the molecular mechanisms of its action have not been established. To establish the molecular mechanisms of CDG against PD, we used TCM network pharmacology methods to predict its molecular targets and signaling pathways, followed by experimental validation. The Core Protein protein interaction (PPI) network of the 150 intersections between CDG and PD-related genes, comprising 23 proteins, including CASP3 (caspase-3), MAPK8 (JNK), FOS (c-Fos), and JUN (c-Jun). KEGG and GO analyses revealed that apoptotic regulation and MAPK signaling pathways were significantly enriched. Since c-Jun and c-Fos are AP-1 subunits, an important downstream JNK effector, we investigated if the JNK/AP-1 pathway influences CDG against apoptosis through the nigrostriatal pathways in PD rat models. Molecular docking analysis found that the top three bioactive compounds exhibiting the highest Degree Centrality following online database and LC-MS analysis had high affinities for JNK. Experimental validation analysis showed that CDG decreased the number of rotating laps and suppressed the levels of phosphorylated c-Jun, c-Fos, and JNK, as well as the number of TUNEL positive cells and the cleaved caspase-3 level in the nigrostriatal pathway. Furthermore, CDG treatment elevated the number of TH neurons, TH expression level, and Bcl-2/Bax protein ratio in a 6-OHDA-induced PD rat. These findings are in tandem with those obtained using SP600125, a specific JNK inhibitor. In conclusion, CDG suppresses the apoptosis of the nigrostriatal pathway and relieves PD symptoms by suppressing the JNK/AP-1 signaling pathway.

scholarly journals Free Radical-derived Oxysterols: Novel Adipokines Modulating Adipogenic Differentiation of Adipose Precursor Cells

2016 ◽  
Vol 101 (12) ◽  
pp. 4974-4983 ◽  
Author(s):  
Giuseppe Murdolo ◽  
Marta Piroddi ◽  
Cristina Tortoioli ◽  
Desirée Bartolini ◽  
Martin Schmelz ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Free Radical ◽  
Cell Viability ◽  
Signaling Pathways ◽  
Adipogenic Differentiation ◽  
Primary Cultures ◽  
Mapk Signaling ◽  
Precursor Cells ◽  
Gas Chromatography Mass Spectrometry ◽  
Type I

Context: Increased oxidative stress in adipose tissue emerges as an inducer of obesity-linked insulin resistance. Here we tested whether free-radical derived oxysterols are formed by, and accumulate in, human adipocytes. Moreover, we asked whether increased accumulation of oxysterols characterizes the adipose cells of obese patients with type 2 diabetes (T2D) (OBT2D) compared with lean, nondiabetic controls (CTRLs). Finally, we studied the effects of the free radical–derived oxysterols on adipogenic differentiation of adipose-derived stem cells (ASCs). Main Outcome Measures: Adipocytes and ASCs were isolated from sc abdominal adipose tissue biopsy in four OBT2D and four CTRL subjects. Oxysterols in adipocytes were detected by gas chromatography/mass spectrometry. The cellular and molecular effects of oxysterols were then evaluated on primary cultures of ASCs focusing on cell viability, adipogenic differentiation, and “canonical” WNT and MAPK signaling pathways. Results: 7-ketocholesterol (7κ-C) and 7β-hydroxycholesterol were unambiguously detected in adipocytes, which showed higher oxysterol accumulation (P < .01) in OBT2D, as compared with CTRL individuals. Notably, the accumulation of oxysterols in adipocytes was predicted by the adipose cell size of the donor (R2 = 0.582; P < .01). Challenging ASCs with free radical–derived type I (7κ-C) and type II (5,6-Secosterol) oxysterols led to a time- and concentration-dependent decrease of cell viability. Meaningfully, at a non-toxic concentration (1μM), these bioactive lipids hampered adipogenic differentiation of ASCs by sequential activation of WNT/β-catenin, p38-MAPK, ERK1/2, and JNK signaling pathways. Conclusion: Free radical–derived oxysterols accumulate in the “diabetic” fat and may act as novel adipokines modulating the adipogenic potential of undifferentiated adipose precursor cells.

scholarly journals Morin Induces Melanogenesis via Activation of MAPK Signaling Pathways in B16F10 Mouse Melanoma Cells

Molecules ◽  
2021 ◽  
Vol 26 (8) ◽  
pp. 2150
Author(s):  
SeoYeon Shin ◽  
JaeYeon Ko ◽  
MinJeong Kim ◽  
Nuri Song ◽  
KyungMok Park
Keyword(s):  
Protein Expression ◽  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Melanoma Cells ◽  
Mapk Signaling ◽  
Tyrosinase Activity ◽  
Melanin Biosynthesis ◽  
Mouse Melanoma ◽  
Melanin Contents ◽  
Mapk Signaling Pathways

Morin is a well-known flavonoid, and has been reported to have various properties, such as anti-cell death, antioxidant, and anti-inflammatory properties. Although studies on the biochemical and biological actions of morin have been reported, the melanin biosynthesis effects and molecular mechanisms are unknown. In this study, we first found that morin has the effect of enhancing melanin biosynthesis in B16F10 mouse melanoma cells, and analyzed the molecular mechanism. In this study, we examined the effects of morin on the melanin contents and tyrosinase activity, as well as the protein expression levels of the melanogenic enzymes TRP-1, TRP-2, and microphtalmia-associated transcription factor (MITF) in B16F10 mouse melanoma cells. Morin showed no cytotoxicity in the concentration range of 5–100 μM, and significantly increased the intracellular tyrosinase activity and melanin contents. In mechanism analysis, morin increased the protein expression of TRP-1, TRP-2, and MITF associated with melanogenesis. Furthermore, morin increased phosphorylated ERK and p38 at the early time, and decreased phosphorylated ERK after 12 h. The results suggest that morin enhances melanin synthesis through the MAPK signaling pathways in B16F10 mouse melanoma cells.

scholarly journals Simvastatin and ROCK Inhibitor Y-27632 Inhibit Myofibroblast Differentiation of Graves’ Ophthalmopathy-Derived Orbital Fibroblasts via RhoA-Mediated ERK and p38 Signaling Pathways

2021 ◽  
Vol 11 ◽  
Author(s):  
Yi-Hsuan Wei ◽  
Shu-Lang Liao ◽  
Sen-Hsu Wang ◽  
Chia-Chun Wang ◽  
Chang-Hao Yang
Keyword(s):  
Signaling Pathways ◽  
Molecular Mechanisms ◽  
Transforming Growth Factor ◽  
Smooth Muscle Actin ◽  
Transforming Growth Factor Β ◽  
Mapk Signaling ◽  
Myofibroblast Differentiation ◽  
Rock Inhibitor ◽  
Graves Ophthalmopathy ◽  
Orbital Fibroblasts

Transforming growth factor-β (TGF-β)-induced differentiation of orbital fibroblasts into myofibroblasts is an important pathogenesis of Graves’ ophthalmopathy (GO) and leads to orbital tissue fibrosis. In the present study, we explored the antifibrotic effects of simvastatin and ROCK inhibitor Y-27632 in primary cultured GO orbital fibroblasts and tried to explain the molecular mechanisms behind these effects. Both simvastatin and Y-27632 inhibited TGF-β-induced α-smooth muscle actin (α-SMA) expression, which serves as a marker of fibrosis. The inhibitory effect of simvastatin on TGF-β-induced RhoA, ROCK1, and α-SMA expression could be reversed by geranylgeranyl pyrophosphate, an intermediate in the biosynthesis of cholesterol. This suggested that the mechanism of simvastatin-mediated antifibrotic effects may involve RhoA/ROCK signaling. Furthermore, simvastatin and Y-27632 suppressed TGF-β-induced phosphorylation of ERK and p38. The TGF-β-mediated α-SMA expression was suppressed by pharmacological inhibitors of p38 and ERK. These results suggested that simvastatin inhibits TGF-β-induced myofibroblast differentiation via suppression of the RhoA/ROCK/ERK and p38 MAPK signaling pathways. Thus, our study provides evidence that simvastatin and ROCK inhibitors may be potential therapeutic drugs for the prevention and treatment of orbital fibrosis in GO.

scholarly journals Hypoxia Activates Notch4 via ERK/JNK/P38 MAPK Signaling Pathways to Promote Lung Adenocarcinoma Progression and Metastasis

2021 ◽  
Vol 9 ◽  
Author(s):  
Xiaochen Li ◽  
Xiaopei Cao ◽  
Hanqiu Zhao ◽  
Mingzhou Guo ◽  
Xiaoyu Fang ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mapk Signaling ◽  
Binding Interaction ◽  
Lung Cancer Patients ◽  
Cell Progression ◽  
Mapk Signaling Pathways

Hypoxia contributes to the progression and metastasis of lung adenocarcinoma (LUAD). However, the specific underlying molecular mechanisms have not been fully elucidated. Here we report that Notch4 is upregulated in lung tissue from lung cancer patients. Functionally, Hypoxia activates the expressions of Delta-like 4 and Notch4, resulting in the excessive proliferation and migration of LUAD cells as well as apoptotic resistance. Notch4 silencing reduced ERK, JNK, and P38 activation. Meanwhile, Notch4 overexpression enhanced ERK, JNK, and P38 activation in LUAD cells. Furthermore, Notch4 exerted pro-proliferation, anti-apoptosis and pro-migration effects on LUAD cells that were partly reversed by the inhibitors of ERK, JNK, and p38. The binding interaction between Notch4 and ERK/JNK/P38 were confirmed by the co-immunoprecipitation assay. In vivo study revealed that Notch4 played a key role in the growth and metastasis of LUAD using two xenograft models. This study demonstrates that hypoxia activates Notch4-ERK/JNK/P38 MAPK signaling pathways to promote LUAD cell progression and metastasis.

4-Acetylantrocamol LT3, a New Ubiquinone from Antrodia cinnamomea, Inhibits Hepatocellular Carcinoma HepG2 Cell Growth by Targeting YAP/TAZ, mTOR, and WNT/β-Catenin Signaling

2020 ◽  
Vol 48 (05) ◽  
pp. 1243-1261 ◽  
Author(s):  
Yen-Lin Chen ◽  
I-Chuan Yen ◽  
Kuen-Tze Lin ◽  
Feng-Yi Lai ◽  
Shih-Yu Lee
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cell Growth ◽  
Cell Viability ◽  
Signaling Pathways ◽  
Hepg2 Cell ◽  
Colony Formation ◽  
Molecular Mechanisms ◽  
Binding Motif ◽  
Dependent Manner ◽  
Antrodia Cinnamomea

4-acetylantrocamol LT3 (4AALT3), a new ubiquinone from the mycelium of Antrodia cinnamomea (Polyporaceae), has been recently shown to possess anticancer activity. However, the detailed mechanisms of such action remain unclear. In this study, the molecular mechanisms of 4AALT3 on hepatocellular carcinoma cells (HCC) were investigated. Human hepatocellular carcinoma cell line HepG2 cells were treated with concentrations of 4AALT3. Cell viability, colony formation, and the underlying mechanisms were then analyzed by CCK-8, colony formation, qPCR, and Western blotting assays. We found that 4AALT3 significantly decreased cell viability and colony formation in a dose-dependent manner. Accordingly, 4AALT3 significantly decreased protein levels of cyclin B, E1, D1, and D3, thereby facilitating cell cycle arrest. In addition, 4AALT3 significantly suppressed the nuclear localization of Yes-associated protein (YAP)/transcriptional co-activator with PDZ-binding motif (TAZ), mammalian target of rapamycin (mTOR), and WNT/[Formula: see text]-catenin signaling pathways, all of which are well-known signaling pathways that contribute to the malignant properties of HCC. These effects are associated with activation of 5′ AMP-activated protein kinase (AMPK) and autophagy. Our findings indicate that 4AALT3 exerts inhibitory effects on HepG2 cell growth via multiple signaling pathways and may be a potential agent for HCC therapy.

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