scholarly journals Hydrogen sulfide upregulates acid-sensing ion channels via the MAPK-Erk1/2 signaling pathway

Function ◽  
2021 ◽  
Author(s):  
Zhong Peng ◽  
Stephan Kellenberger
Keyword(s):  
Hydrogen Sulfide ◽  
Ion Channels ◽  
Signaling Pathway ◽  
Cortical Neurons ◽  
Mammalian Cells ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Membrane Expression ◽  
Concentration Dependent Manner ◽  
Acid Sensing Ion Channels

Abstract Hydrogen sulfide (H2S) emerged recently as a new gasotransmitter and was shown to exert cellular effects by interacting with proteins, among them many ion channels. Acid-sensing ion channels (ASICs) are neuronal voltage-insensitive Na+ channels activated by extracellular protons. ASICs are involved in many physiological and pathological processes, such as fear conditioning, pain sensation and seizures. We characterize here the regulation of ASICs by H2S. In transfected mammalian cells, the H2S donor NaHS increased the acid-induced ASIC1a peak currents in a time- and concentration-dependent manner. Similarly, NaHS potentiated also the acid-induced currents of ASIC1b, ASIC2a and ASIC3. An upregulation induced by the H2S donors NaHS and GYY4137 was also observed with the endogenous ASIC currents of cultured hypothalamus neurons. In parallel with the effect on function, the total and plasma membrane expression of ASIC1a was increased by GYY4137, as determined in cultured cortical neurons. H2S also enhanced the phosphorylation of extracellular signal-regulated kinase, which belongs to the family of mitogen-activated protein kinases (MAPKs). Pharmacological blockade of the MAPK signaling pathway prevented the GYY4137-induced increase of ASIC function and expression, indicating that this pathway is required for ASIC regulation by H2S. Our study demonstrates that H2S regulates ASIC expression and function, and identifies the involved signaling mechanism. Since H2S shares several roles with ASICs, as e.g. facilitation of learning and memory, protection during seizure activity and modulation of nociception, it may be possible that H2S exerts some of these effects via a regulation of ASIC function.

scholarly journals Glycinin-induced porcine IPEC-J2 cells damage via the NF-κB/MAPK signaling pathway

2020 ◽  
Author(s):  
Chenglu Peng ◽  
Zhifeng Sun ◽  
Lei Wang ◽  
Yingshuang Shu ◽  
Mengchu He ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Intestinal Barrier ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Control Group ◽  
Epithelial Cell Line ◽  
Pyrrolidine Dithiocarbamate ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Nitric Oxide Synthase Inhibitor

Abstract Background: Glycinin, a protein found in soybean, is a human and animal allergen that causes damage to the intestinal barrier. However, its mechanisms of action remain unclear. Therefore, in this study, the intestinal porcine epithelial cell line IPEC-J2 was used to evaluate the effect of glycinin concentration on the intestinal epithelium and identify the related signaling pathways. Results: IPEC-J2 cells were divided into seven treatment groups and a control group; the cells were treated for 24 h with 1, 5, or 10 mg/mL glycinin or with 5 mg/mL glycinin after 30 min of pre-treatment with 1 μmol/L nuclear factor-kappa B (NF-κB) inhibitor (pyrrolidine dithiocarbamate), inducible nitric oxide synthase inhibitor ( N -ω-nitro-l-arginine methyl ester), Jun N-terminal kinase (JNK) inhibitor (SP600125), or p38 inhibitor (SB202190). A series of molecular and biochemical experiments revealed that the levels of NF-κB, p38, and JNK, as well as their downstream proteins, were increased after treatment compared to those in the control group. Conclusion: Glycinin damaged IPEC-J2 cells in a concentration-dependent manner via the NF-κB/MAPK signaling pathway.

The Anti-Atherogenic Properties of Sesamin are Mediated via Improved Macrophage Cholesterol Efflux Through PPARγ1-LXRα and MAPK Signaling

2014 ◽  
Vol 84 (1-2) ◽  
pp. 79-91 ◽  
Author(s):  
Amin F. Majdalawieh ◽  
Hyo-Sung Ro
Keyword(s):  
Cholesterol Efflux ◽  
Transcriptional Activity ◽  
Molecular Mechanisms ◽  
Foam Cell ◽  
Mapk Signaling ◽  
Luciferase Reporter ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Macrophage Cholesterol Efflux

Background: Foam cell formation resulting from disrupted macrophage cholesterol efflux, which is triggered by PPARγ1 and LXRα, is a hallmark of atherosclerosis. Sesamin and sesame oil exert anti-atherogenic effects in vivo. However, the exact molecular mechanisms underlying such effects are not fully understood. Aim: This study examines the potential effects of sesamin (0, 25, 50, 75, 100 μM) on PPARγ1 and LXRα expression and transcriptional activity as well as macrophage cholesterol efflux. Methods: PPARγ1 and LXRα expression and transcriptional activity are assessed by luciferase reporter assays. Macrophage cholesterol efflux is evaluated by ApoAI-specific cholesterol efflux assays. Results: The 50 μM, 75 μM, and 100 μM concentrations of sesamin up-regulated the expression of PPARγ1 (p< 0.001, p < 0.001, p < 0.001, respectively) and LXRα (p = 0.002, p < 0.001, p < 0.001, respectively) in a concentration-dependent manner. Moreover, 75 μM and 100 μM concentrations of sesamin led to 5.2-fold (p < 0.001) and 6.0-fold (p<0.001) increases in PPAR transcriptional activity and 3.9-fold (p< 0.001) and 4.2-fold (p < 0.001) increases in LXR transcriptional activity, respectively, in a concentration- and time-dependent manner via MAPK signaling. Consistently, 50 μM, 75 μM, and 100 μM concentrations of sesamin improved macrophage cholesterol efflux by 2.7-fold (p < 0.001), 4.2-fold (p < 0.001), and 4.2-fold (p < 0.001), respectively, via MAPK signaling. Conclusion: Our findings shed light on the molecular mechanism(s) underlying sesamin’s anti-atherogenic effects, which seem to be due, at least in part, to its ability to up-regulate PPARγ1 and LXRα expression and transcriptional activity, improving macrophage cholesterol efflux. We anticipate that sesamin may be used as a therapeutic agent for treating atherosclerosis.

scholarly journals The Carbamate, Physostigmine does not Impair Axonal Transport in Rat Cortical Neurons

2021 ◽  
Vol 16 ◽  
pp. 263310552110202
Author(s):  
Sean X Naughton ◽  
Wayne D Beck ◽  
Zhe Wei ◽  
Guangyu Wu ◽  
Peter W Baas ◽  
...  
Keyword(s):  
Axonal Transport ◽  
Cortical Neurons ◽  
Acetylcholinesterase Inhibitors ◽  
Neurological Deficits ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Rat Cortical Neurons ◽  
Toxicological Mechanism

Among the various chemicals that are commonly used as pesticides, organophosphates (OPs), and to a lesser extent, carbamates, are most frequently associated with adverse long-term neurological consequences. OPs and the carbamate, pyridostigmine, used as a prophylactic drug against potential nerve agent attacks, have also been implicated in Gulf War Illness (GWI), which is often characterized by chronic neurological symptoms. While most OP- and carbamate-based pesticides, and pyridostigmine are relatively potent acetylcholinesterase inhibitors (AChEIs), this toxicological mechanism is inadequate to explain their long-term health effects, especially when no signs of acute cholinergic toxicity are exhibited. Our previous work suggests that a potential mechanism of the long-term neurological deficits associated with OPs is impairment of axonal transport (AXT); however, we had not previously evaluated carbamates for this effect. Here we thus evaluated the carbamate, physostigmine (PHY), a highly potent AChEI, on AXT using an in vitro neuronal live imaging assay that we have previously found to be very sensitive to OP-related deficits in AXT. We first evaluated the OP, diisopropylfluorophosphate (DFP) (concentration range 0.001-10.0 µM) as a reference compound that we found previously to impair AXT and subsequently evaluated PHY (concentration range 0.01-100 nM). As expected, DFP impaired AXT in a concentration-dependent manner, replicating our previously published results. In contrast, none of the concentrations of PHY (including concentrations well above the threshold for impairing AChE) impaired AXT. These data suggest that the long-term neurological deficits associated with some carbamates are not likely due to acute impairments of AXT.

The defense response of Caenorhabditis elegans to Cutibacterium acnes SK137 via the TIR-1-p38 MAPK signaling pathway

2021 ◽  
Author(s):  
Ayano Tsuru ◽  
Yumi Hamazaki ◽  
Shuta Tomida ◽  
Mohammad Shaokat Ali ◽  
Eriko Kage-Nakadai
Keyword(s):  
Caenorhabditis Elegans ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Defense Response ◽  
Mapk Pathway ◽  
Defense Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Healthy Skin ◽  
Cutibacterium Acnes

Abstract Cutibacterium acnes plays roles in both acne disease and healthy skin ecosystem. We observed that mutations in the tir-1/SARM1 and p38 MAPK cascade genes significantly shortened Caenorhabditis elegans lifespan upon Cutibacterium acnes SK137 infection. Antimicrobial molecules were induced by SK137 in a TIR-1-dependent manner. These results suggest that defense responses against SK137 involve the TIR-1-p38 MAPK pathway in Caenorhabditis elegans.

Cell surface interactions in conjugation: Tetrahymena ciliary membrane vesicles

1984 ◽  
Vol 4 (4) ◽  
pp. 681-687
Author(s):  
B Love ◽  
M B Rotheim
Keyword(s):  
Cell Surface ◽  
Mating Type ◽  
Mammalian Cells ◽  
Membrane Vesicles ◽  
Surface Interactions ◽  
Dependent Manner ◽  
Concentration Dependent Manner ◽  
Ciliary Membrane ◽  
Adhesion Sites ◽  
Cell Surface Interactions

Tetrahymena ciliary membrane vesicles are shown to interact with preconjugant cells in a mating type-specific way. When cells are treated with vesicles of a different mating type before mixing for conjugation, cell pairing is enhanced, and the normal prepairing period is partially eliminated. This enhancement is mating type specific since it is not observed after pretreatment of cells with vesicles of their own mating type. In contrast, when vesicles are added at the time of mixing of two starved cultures, cell pairing is delayed in a concentration-dependent manner. By varying the conditions, we demonstrated enhancement or inhibition, or both. These results are interpreted in terms of two independent interactions of cells with vesicles. We suggest that first, vesicles substitute for another cell in cell-cell prepairing interaction and second, vesicles compete for adhesion sites produced during the prepairing period. Finally, the data presented are summarized within a speculative framework that calls attention to potential analogies with hormone-receptor signaling in mammalian cells.

scholarly journals Inhibition of HepG-2 Cells (Liver Cancer Cell Line) Viability by 3-Hydroxypyridine-2-Carboxaldehyde N(4)-Methylthiosemicarbazone

2021 ◽  
Vol 8 (2) ◽  
pp. 88-97
Author(s):  
Edrees Khan Rahmatzada ◽  
Prof. Paras Nath Yadav ◽  
Dr. Yuba Raj Pokharel
Keyword(s):  
Cancer Cell Line ◽  
Mapk Signaling ◽  
In Vivo Model ◽  
Dependent Manner ◽  
Dapi Staining ◽  
Concentration Dependent Manner ◽  
Anticancer Effects ◽  
Ic50 Value ◽  
Colony Number

Thiosemicarbazone have the antiviral, antibacterial, antifungal, and anticancer effects. 3-OH-Me-TSC inhibited the cell viability of HepG-2 cells by CV assay in a concentration dependent manner (control, 1μM, 3μM, 10μM, 30μM, and 100μM) with IC50 value of 9.587622μM. Further colony formation assay demonstrated that 3-OH-Me-TSC inhibits colony number and size of HepG-2. Wound healing assay exhibited that 3-OH-Me-TSC inhibit the migration of HepG-2 cells. DAPI staining showed that 3-OH-Me-TSC inhibited proliferation of HepG-2 cells in 30μM and 100μM concentrations respectively. 3-OH-Me-TSC inhibited VEGF, p38 alpha, C-JUN, BECN-1, ERK, NF-KB, in HepG-2 cells. We found that 3-OH-Me-TSC inhibit proliferation of HepG-2 cells by inhibiting MAPK signaling pathway, 3-OH-Me-TSC can be developed as future chemotherapeutic agent for treatment of hepatocellular carcinoma after the evaluation of this compounds in more cancer cells an in vivo model.

scholarly journals Intracerebral Injection of Heme Induces Lipid Peroxidation, Neuroinflammation, and Sensorimotor Deficits

Stroke ◽  
2021 ◽  
Author(s):  
Luiz Ricardo C. Vasconcellos ◽  
Letícia Martimiano ◽  
Danillo Pereira Dantas ◽  
Filipe Mota Fonseca ◽  
Hilton Mata-Santos ◽  
...  
Keyword(s):  
Lipid Peroxidation ◽  
Signaling Pathway ◽  
Brain Damage ◽  
Autologous Blood ◽  
Mapk Signaling ◽  
Heme Oxygenase 1 ◽  
Dependent Manner ◽  
In Vivo Models ◽  
Sensorimotor Deficits ◽  
The Brain

Background and Purpose: Heme is a red blood cell component released in the brain parenchyma following intracerebral hemorrhage. However, the study of the pathophysiological mechanisms triggered by heme in the brain is hampered by the lack of well-established in vivo models of intracerebral heme injection. This study aims to optimize and characterize a protocol of intrastriatal heme injection in mice, with a focus on the induction of lipid peroxidation, neuroinflammation and, ultimately, sensorimotor deficits. We also evaluated the involvement of NLRP3 (NOD-, LRR-, and pyrin domain-containing protein 3), an inflammasome sensor, in the behavior deficits induced by heme in this model. Methods: Mice were injected with heme in the striatum for the evaluation of neuroinflammation and brain damage through histological and biochemical techniques. Immunoblot was used to evaluate the expression of proteins involved in heme/iron metabolism and antioxidant responses and the activation of the MAPK (mitogen-activated protein kinase) signaling pathway. For the assessment of neurological function, we followed-up heme-injected mice for 2 weeks using the rotarod, elevated body swing, and cylinder tests. Mice injected with the vehicle (sham), or autologous blood were used as controls. Results: Heme induced lipid peroxidation and inflammation in the brain. Moreover, heme increased the expression of HO-1 (heme oxygenase-1), ferritin, p62, and superoxide dismutase 2, and activated the MAPK signaling pathway promoting pro-IL (interleukin)-1β production and its cleavage to the active form. Heme-injected mice exhibited signs of brain damage and reactive astrogliosis around the injection site. Behavior deficits were observed after heme or autologous blood injection in comparison to sham-operated controls. In addition, behavior deficits and IL-1β production were reduced in Nlrp3 knockout mice in comparison to wild-type mice. Conclusions: Our results show that intracerebral heme injection induces neuroinflammation, and neurological deficits, in an NLRP3-dependent manner, suggesting that this is a feasible model to evaluate the role of heme in neurological disorders.

scholarly journals In the Model Host Caenorhabditis elegans, Sphingosine-1-Phosphate-Mediated Signaling Increases Immunity toward Human Opportunistic Bacteria

2020 ◽  
Vol 21 (21) ◽  
pp. 7813
Author(s):  
Kiho Lee ◽  
Iliana Escobar ◽  
Yeeun Jang ◽  
Wooseong Kim ◽  
Frederick M. Ausubel ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Stress Responses ◽  
Mapk Signaling ◽  
Dependent Manner ◽  
Cellular Functions ◽  
Kinase Gene ◽  
Concentration Dependent Manner ◽  
C Elegans ◽  
Opportunistic Bacteria ◽  
Free Living Nematode

Sphingosine-1-phophate (S1P) is a sphingolipid-derived signaling molecule that controls diverse cellular functions including cell growth, homeostasis, and stress responses. In a variety of metazoans, cytosolic S1P is transported into the extracellular space where it activates S1P receptors in a concentration-dependent manner. In the free-living nematode Caenorhabditis elegans, the spin-2 gene, which encodes a S1P transporter, is activated during Gram-positive or Gram-negative bacterial infection of the intestine. However, the role during infection of spin-2 and three additional genes in the C. elegans genome encoding other putative S1P transporters has not been elucidated. Here, we report an evolutionally conserved function for S1P and a non-canonical role for S1P transporters in the C. elegans immune response to bacterial pathogens. We found that mutations in the sphingosine kinase gene (sphk-1) or in the S1P transporter genes spin-2 or spin-3 decreased nematode survival after infection with Pseudomonas aeruginosa or Enterococcus faecalis. In contrast to spin-2 and spin-3, mutating spin-1 leads to an increase in resistance to P. aeruginosa. Consistent with these results, when wild-type C. elegans were supplemented with extracellular S1P, we found an increase in their lifespan when challenged with P. aeruginosa and E. faecalis. In comparison, spin-2 and spin-3 mutations suppressed the ability of S1P to rescue the worms from pathogen-mediated killing, whereas the spin-1 mutation had no effect on the immune-enhancing activity of S1P. S1P demonstrated no antimicrobial activity toward P. aeruginosa and Escherichia coli and only minimal activity against E. faecalis MMH594 (40 µM). These data suggest that spin-2 and spin-3, on the one hand, and spin-1, on the other hand, transport S1P across cellular membranes in opposite directions. Finally, the immune modulatory effect of S1P was diminished in C. eleganssek-1 and pmk-1 mutants, suggesting that the immunomodulatory effects of S1P are mediated by the p38 MAPK signaling pathway.

scholarly journals Hair Growth Effect of Emulsion Extracted Brevilin A, a JAK3 Inhibitor, from Centipeda minima

Processes ◽  
2020 ◽  
Vol 8 (7) ◽  
pp. 767
Author(s):  
Byoung Ha Kim ◽  
Won-Yung Lee ◽  
Tuy An Trinh ◽  
Jae Sung Pyo ◽  
Sooyeun Lee ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Hair Growth ◽  
Mapk Signaling ◽  
Janus Kinase ◽  
Gene Set Enrichment Analysis ◽  
Herbal Extract ◽  
Growth Effect ◽  
Dependent Manner ◽  
Centipeda Minima ◽  
Jak3 Inhibitor

Janus kinase 3 (JAK3) inhibitors have been used effectively in the treatment of several cases of alopecia universalis and its variants. Our study aims to evaluate whether the emulsion extract of brevilin A from Centipeda minima (CMX) stimulates hair regrowth in a clinical trial, as a JAK3 inhibitor, combined with network pharmacology-based analysis. CMX showed potent inhibition of JAK3 in a concentration-dependent manner. Significant differences in total hair count, terminal hair count, and anagen hair count from the baseline to 24 weeks were observed between the placebo and CMX subjects. The gene set enrichment analysis showed that the targets of CMX are mainly associated with the JAK-STAT signaling pathway, cytokine–cytokine receptor interactions, and the MAPK signaling pathway. This study suggests that the medicinal herbal extract CMX is useful in the treatment of mild to moderate vertex balding that contribute to the visible improvements in hair growth observed in treated patients.

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