scholarly journals The Therapeutic Effect of Curcumin in Quinolinic Acid-Induced Neurotoxicity in Rats is Associated with BDNF, ERK1/2, Nrf2, and Antioxidant Enzymes

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 388 ◽  
Author(s):  
Ricardo A. Santana-Martínez ◽  
Carlos A. Silva-Islas ◽  
Yessica Y. Fernández-Orihuela ◽  
Diana Barrera-Oviedo ◽  
José Pedraza-Chaverri ◽  
...  
Keyword(s):  
Therapeutic Effect ◽  
Quinolinic Acid ◽  
Antioxidant Defense System ◽  
Mitogen Activated Protein Kinase ◽  
Motor Deficit ◽  
Related Factor ◽  
Morphological Alterations ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Neurotropic Factor

In the present study we investigated the participation of brain-derived neurotropic factor (BDNF) on the activation of the mitogen activated protein kinase (MAPK) protein extracellular signal-regulated kinase-1/2 (ERK1/2) as a mechanism of curcumin (CUR) to provide an antioxidant defense system mediated by the nuclear factor erythroid 2-related factor 2 (Nrf2) in the neurotoxic model induced by quinolinic acid (QUIN). Wistar rats received CUR (400 mg/kg, intragastrically) for 6 days after intrastriatal injection with QUIN (240 nmol). CUR improved the motor deficit and morphological alterations induced by QUIN and restored BDNF, ERK1/2, and Nrf2 levels. CUR treatment avoided the decrease in the protein levels of glutathione peroxidase (GPx), glutathione reductase (GR), γ-glutamylcysteine ligase (γ-GCL), and glutathione (GSH) levels. Only, the QUIN-induced decrease in the GR activity was prevented by CUR treatment. Finally, QUIN increased superoxide dismutase 2 (SOD2) and catalase (CAT) levels, and the γGCL and CAT activities; however, this increase was major in the QUIN+CUR group for γ-GCL, CAT, and SOD activities. These data suggest that the therapeutic effect of CUR could involve BDNF action on the activation of ERK1/2 to induce increased levels of protein and enzyme activity of antioxidant proteins regulated by Nrf2 and GSH levels.

scholarly journals Banhasasim-Tang Treatment Reduces the Severity of Esophageal Mucosal Ulcer on Chronic Acid Reflux Esophagitis in Rats

2017 ◽  
Vol 2017 ◽  
pp. 1-10 ◽  
Author(s):  
Mi-Rae Shin ◽  
Bu-Il Seo ◽  
Chang Gue Son ◽  
Seong-Soo Roh ◽  
Hyo-Jin An
Keyword(s):  
Reflux Esophagitis ◽  
Thiobarbituric Acid ◽  
Antioxidant Response ◽  
Acid Reflux ◽  
Mitogen Activated Protein Kinase ◽  
Histological Evaluation ◽  
Related Factor ◽  
Nuclear Factor ◽  
Protein Levels ◽  
Mitogen Activated Protein

The present study was conducted to evaluate both antioxidant and anti-inflammatory activity of Banhasasim-tang (BHSST) on chronic acid reflux esophagitis (CRE) model. Rat CRE model was established operatively and then treated with BHSST (1 g/kg body weight per day) for 15 days Esophageal pathological changes were analyzed using macroscopic examination and hematoxylin/eosin staining. The antioxidant and inflammatory protein levels were determined using Western blotting. The administration of BHSST significantly reduced both the overexpression of serum reactive oxygen species (ROS) and an excessive formation of thiobarbituric acid-reactive substances (TBARS) in esophagus tissue. Thus, the severity of esophageal ulcer was lower in BHSST treated rats than control rats on the gross and histological evaluation. Nuclear factor-erythroid 2-related factor 2 (Nrf2) led to the upregulation of antioxidant enzyme including SOD, GPx-1/2, and HO-1 by binding to antioxidant response element (ARE). Moreover, BHSST administration markedly reduced the expression of inflammatory proteins through mitogen-activated protein kinase- (MAPK-) related signaling pathways and decreased significantly the protein expressions of inflammatory mediators and cytokines by inhibition of nuclear factor-kappa B (NF-κB) activation. Taken together, these results support the fact that BHSST administration can suppress the development of esophageal mucosal ulcerviaregulating inflammation through the activation of the antioxidant pathway.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals Coordinated Regulation of Insulin Signaling by the Protein Tyrosine Phosphatases PTP1B and TCPTP

2005 ◽  
Vol 25 (2) ◽  
pp. 819-829 ◽  
Author(s):  
Sandra Galic ◽  
Christine Hauser ◽  
Barbara B. Kahn ◽  
Fawaz G. Haj ◽  
Benjamin G. Neel ◽  
...  
Keyword(s):  
Insulin Signaling ◽  
Tyrosine Phosphatase ◽  
Protein Tyrosine Phosphatases ◽  
Negative Regulator ◽  
Mitogen Activated Protein Kinase ◽  
Protein Tyrosine ◽  
Akt Activation ◽  
Protein Levels ◽  
Mitogen Activated Protein

ABSTRACT The protein tyrosine phosphatase PTP1B is a negative regulator of insulin signaling and a therapeutic target for type 2 diabetes. Our previous studies have shown that the closely related tyrosine phosphatase TCPTP might also contribute to the regulation of insulin receptor (IR) signaling in vivo (S. Galic, M. Klingler-Hoffmann, M. T. Fodero-Tavoletti, M. A. Puryer, T. C. Meng, N. K. Tonks, and T. Tiganis, Mol. Cell. Biol. 23:2096-2108, 2003). Here we show that PTP1B and TCPTP function in a coordinated and temporally distinct manner to achieve an overall regulation of IR phosphorylation and signaling. Whereas insulin-induced phosphatidylinositol 3-kinase/Akt signaling was prolonged in both TCPTP−/− and PTP1B−/− immortalized mouse embryo fibroblasts (MEFs), mitogen-activated protein kinase ERK1/2 signaling was elevated only in PTP1B-null MEFs. By using phosphorylation-specific antibodies, we demonstrate that both IR β-subunit Y1162/Y1163 and Y972 phosphorylation are elevated in PTP1B−/− MEFs, whereas Y972 phosphorylation was elevated and Y1162/Y1163 phosphorylation was sustained in TCPTP−/− MEFs, indicating that PTP1B and TCPTP differentially contribute to the regulation of IR phosphorylation and signaling. Consistent with this, suppression of TCPTP protein levels by RNA interference in PTP1B−/− MEFs resulted in no change in ERK1/2 signaling but caused prolonged Akt activation and Y1162/Y1163 phosphorylation. These results demonstrate that PTP1B and TCPTP are not redundant in insulin signaling and that they act to control both common as well as distinct insulin signaling pathways in the same cell.

scholarly journals Short-Term Microgravity Influences Cell Adhesion in Human Breast Cancer Cells

2019 ◽  
Vol 20 (22) ◽  
pp. 5730 ◽  
Author(s):  
Mohamed Zakaria Nassef ◽  
Sascha Kopp ◽  
Daniela Melnik ◽  
Thomas J. Corydon ◽  
Jayashree Sahana ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Adhesion ◽  
Parabolic Flight ◽  
Three Dimensional ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Protective Mechanisms ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Real Microgravity

With the commercialization of spaceflight and the exploration of space, it is important to understand the changes occurring in human cells exposed to real microgravity (r-µg) conditions. We examined the influence of r-µg, simulated microgravity (s-µg, incubator random positioning machine (iRPM)), hypergravity (hyper-g), and vibration (VIB) on triple-negative breast cancer (TNBC) cells (MDA-MB-231 cell line) with the aim to study early changes in the gene expression of factors associated with cell adhesion, apoptosis, nuclear factor “kappa-light-chain-enhancer” of activated B-cells (NF-κB) and mitogen-activated protein kinase (MAPK) signaling. We had the opportunity to attend a parabolic flight (PF) mission and to study changes in RNA transcription in the MDA-MB cells exposed to PF maneuvers (29th Deutsches Zentrum für Luft- und Raumfahrt (DLR) PF campaign). PF maneuvers induced an early up-regulation of ICAM1, CD44 and ERK1 mRNAs after the first parabola (P1) and a delayed upregulation of NFKB1, NFKBIA, NFKBIB, and FAK1 after the last parabola (P31). ICAM-1, VCAM-1 and CD44 protein levels were elevated, whereas the NF-κB subunit p-65 and annexin-A2 protein levels were reduced after the 31st parabola (P31). The PRKCA, RAF1, BAX mRNA were not changed and cleaved caspase-3 was not detectable in MDA-MB-231 cells exposed to PF maneuvers. Hyper-g-exposure of the cells elevated the expression of CD44 and NFKBIA mRNAs, iRPM-exposure downregulated ANXA2 and BAX, whereas VIB did not affect the TNBC cells. The early changes in ICAM-1 and VCAM-1 and the rapid decrease in the NF-κB subunit p-65 might be considered as fast-reacting, gravity-regulated and cell-protective mechanisms of TNBC cells exposed to altered gravity conditions. This data suggest a key role for the detected gravity-signaling elements in three-dimensional growth and metastasis.

scholarly journals Comparison of the protective effects of steamed and cooked broccolis on ischaemia–reperfusion-induced cardiac injury

2009 ◽  
Vol 103 (6) ◽  
pp. 815-823 ◽  
Author(s):  
Subhendu Mukherjee ◽  
Istvan Lekli ◽  
Diptarka Ray ◽  
Hiranmoy Gangopadhyay ◽  
Utpal Raychaudhuri ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Cardiac Injury ◽  
Mitogen Activated Protein Kinase ◽  
Related Factor ◽  
Protective Effects ◽  
Extracellular Signal Regulated Kinase ◽  
Redox Signalling ◽  
Ischaemia Reperfusion ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

Recently, broccoli, a vegetable of the Brassica family, has been found to protect the myocardium from ischaemic reperfusion injury through the redox signalling of sulphoraphane, which is being formed from glucosinolate present in this vegetable. Since cooked broccoli loses most of its glucosinolate, we assumed that fresh broccoli could be a superior cardioprotective agent compared to cooked broccoli. To test this, two groups of rats were fed with fresh (steamed) broccoli or cooked broccoli for 30 d, while a third group was given vehicle only for the same period of time. After 30 d, all the rats were sacrificed, and the isolated working hearts were subjected to 30 min ischaemia followed by 2 h of reperfusion. Both cooked and steamed broccolis displayed significantly improved post-ischaemic ventricular function and reduced myocardial infarction and cardiomyocyte apoptosis compared to control, but steamed broccoli showed superior cardioprotective abilities compared with the cooked broccoli. Corroborating with these results, both cooked and steamed broccolis demonstrated significantly enhanced induction of the survival signalling proteins including Bcl2, Akt, extracellular signal-regulated kinase 1/2, haemoxygenase-1, NFE2 related factor 2, superoxide dismutase (SOD1) and SOD2 and down-regulation of the proteins (e.g. Bax, c-Jun N-terminal kinase, p38 mitogen-activated protein kinase) of the death signalling pathway, steamed broccoli displaying superior results over its cooked counterpart. The expressions of proteins of the thioredoxin (Trx) superfamily including Trx1 and its precursor sulphoraphane, Trx2 and Trx reductase, were enhanced only in the steamed broccoli group. The results of the present study documented superior cardioprotective properties of the steamed broccoli over cooked broccoli because of the ability of fresh broccoli to perform redox signalling of Trx.

scholarly journals Role of Resveratrol in Regulating Cutaneous Functions

2020 ◽  
Vol 2020 ◽  
pp. 1-20 ◽  
Author(s):  
Si Wen ◽  
Jiechen Zhang ◽  
Bin Yang ◽  
Peter M. Elias ◽  
Mao-Qiang Man
Keyword(s):  
Protective Role ◽  
The Body ◽  
Sirtuin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Keratinocyte Differentiation ◽  
Related Factor ◽  
Keratinocyte Proliferation ◽  
Mitogen Activated Protein ◽  
Peptide Expression

Protective role of the skin is against external insults and maintenance of electrolyte homeostasis of the body. Cutaneous dysfunction can account for the development of both cutaneous and systemic disorders. Thus, improvements in cutaneous functions can benefit a number of extracutaneous and cutaneous functions. Resveratrol, a natural ingredient, displays multiple benefits for various systems/organs, including the skin. The benefits of resveratrol for cutaneous functions include stimulation of keratinocyte differentiation and antimicrobial peptide expression, inhibition of keratinocyte proliferation and cutaneous inflammation, UV protection, anticancer, antiaging, and inhibition of melanogenesis. The mechanisms of action of resveratrol include activation of sirtuin 1 and nuclear factor erythroid 2-related factor 2, and inhibition of mitogen-activated protein kinase signaling. Evidence suggests that topical resveratrol could be a valuable alternative not only for daily skin care, but also for the prevention and treatment of various cutaneous disorders. This review summarizes the benefits of resveratrol for cutaneous functions.

scholarly journals Praeruptorin B Mitigates the Metastatic Ability of Human Renal Carcinoma Cells through Targeting CTSC and CTSV Expression

2020 ◽  
Vol 21 (8) ◽  
pp. 2919
Author(s):  
Chia-Liang Lin ◽  
Tung-Wei Hung ◽  
Tsung-Ho Ying ◽  
Chi-Jui Lin ◽  
Yi-Hsien Hsieh ◽  
...  
Keyword(s):  
Growth Factor Receptor ◽  
Cellular Migration ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Antitumor Effects ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Adult Kidney ◽  
Mitogen Activated Protein ◽  
Underlying Mechanisms

Renal cell carcinoma (RCC) is the most common adult kidney cancer, and accounts for 85% of all cases of kidney cancers worldwide. Praeruptorin B (Pra-B) is a bioactive constituent of Peucedanum praeruptorum Dunn and exhibits several pharmacological activities, including potent antitumor effects. However, the anti-RCC effects of Pra-B and their underlying mechanisms are unclear; therefore, we explored the effects of Pra-B on RCC cells in this study. We found that Pra-B nonsignificantly influenced the cell viability of human RCC cell lines 786-O and ACHN at a dose of less than 30 μM for 24 h treatment. Further study revealed that Pra-B potently inhibited the migration and invasion of 786-O and ACHN cells, as well as downregulated the mRNA and protein expression of cathepsin C (CTSC) and cathepsin V (CTSV) of 786-O and ACHN cells. Mechanistically, Pra-B also reduced the protein levels of phospho (p)-epidermal growth factor receptor (EGFR), p-mitogen-activated protein kinase kinase (MEK), and p-extracellular signal-regulated kinases (ERK) in RCC cells. In addition, Pra-B treatment inhibited the effect of EGF on the upregulation of EGFR–MEK–ERK, CTSC and CTSV expression, cellular migration, and invasion of 786-O cells. Our findings are the first to demonstrate that Pra-B can reduce the migration and invasion ability of human RCC cells through suppressing the EGFR-MEK-ERK signaling pathway and subsequently downregulating CTSC and CTSV. This evidence suggests that Pra-B can be developed as an effective antimetastatic agent for the treatment of RCC.

Expression patterns and immunohistochemical analysis of ERK, HRAS and MEK1 proteins during ovarian prehierarchical follicular development in Zi geese (Anser cygnoides)

2019 ◽  
Author(s):  
H. Lu ◽  
C. T. Sello ◽  
C. Liu ◽  
Y. Sui ◽  
C. Xu ◽  
...  
Keyword(s):  
Protein Localization ◽  
Quantitative Polymerase Chain Reaction ◽  
Expression Patterns ◽  
Follicular Development ◽  
Immunohistochemical Analysis ◽  
Mitogen Activated Protein Kinase ◽  
Expression Levels ◽  
Protein Levels ◽  
Spatiotemporal Expression ◽  
Mitogen Activated Protein

The objective of this study was to investigate the spatiotemporal expression levels and protein localization of extracellular regulated MAP kinase (ERK), HRas proto-oncogene, GTPase (HRAS), and mitogen-activated protein kinase kinase 1 (MEK1) genes in ovarian prehierarchical follicles of geese. The prehierarchical follicles from healthy laying geese (n=6) at the age of 35 to 37 weeks were harvested. The relative expression levels of ERK, HRAS, and MEK1 in various sized prehierarchical follicles were detected by real-time quantitative polymerase chain reaction (RT-qPCR), western blotting, and follicular wall localization was investigated by using immunohistochemistry. The results revealed that the candidate genes were expressed differently at mRNA and protein levels at five stages of prehierarchical follicle development. These results suggest that ERK, HRAS, and MEK1 might be associated to the key biological mechanisms regulating Zi geese folliculogenesis.

scholarly journals Elevating the level of Cdc34/Ubc3 ubiquitin-conjugating enzyme in mitosis inhibits association of CENP-E with kinetochores and blocks the metaphase alignment of chromosomes

2001 ◽  
Vol 154 (4) ◽  
pp. 707-718 ◽  
Author(s):  
Leana M. Topper ◽  
Holger Bastians ◽  
Joan V. Ruderman ◽  
Gary J. Gorbsky
Keyword(s):  
Mammalian Cells ◽  
Proteasome Inhibitors ◽  
Metaphase Plate ◽  
Cytoplasmic Dynein ◽  
Mitogen Activated Protein Kinase ◽  
Protein Levels ◽  
Mitogen Activated Protein ◽  
Associated Proteins ◽  
Ubiquitin Conjugating Enzyme ◽  
Conjugating Enzyme

Cdc34/Ubc3 is a ubiquitin-conjugating enzyme that functions in targeting proteins for proteasome-mediated degradation at the G1 to S cell cycle transition. Elevation of Cdc34 protein levels by microinjection of bacterially expressed Cdc34 into mammalian cells at prophase inhibited chromosome congression to the metaphase plate with many chromosomes remaining near the spindle poles. Chromosome condensation and nuclear envelope breakdown occurred normally, and chromosomes showed oscillatory movements along mitotic spindle microtubules. Most injected cells arrested in a prometaphase-like state. Kinetochores, even those of chromosomes that failed to congress, possessed the normal trilaminar plate ultrastructure. The elevation of Cdc34 protein levels in early mitosis selectively blocked centromere protein E (CENP-E), a mitotic kinesin, from associating with kinetochores. Other proteins, including two CENP-E–associated proteins, BubR1 and phospho-p42/p44 mitogen-activated protein kinase, and mitotic centromere-associated kinesin, cytoplasmic dynein, Cdc20, and Mad2, all exhibited normal localization to kinetochores. Proteasome inhibitors did not affect the prometaphase arrest induced by Cdc34 injection. These studies suggest that CENP-E targeting to kinetochores is regulated by ubiquitylation not involving proteasome-mediated degradation.

scholarly journals Functions and Signaling Pathways of Amino Acids in Intestinal Inflammation

2018 ◽  
Vol 2018 ◽  
pp. 1-13 ◽  
Author(s):  
Fang He ◽  
Chenlu Wu ◽  
Pan Li ◽  
Nengzhang Li ◽  
Dong Zhang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Signaling Pathways ◽  
Intestinal Inflammation ◽  
Intestinal Barrier ◽  
Essential Amino Acids ◽  
Mitogen Activated Protein Kinase ◽  
Related Factor ◽  
Calcium Sensing ◽  
Mitogen Activated Protein ◽  
Irritable Bowel

Intestine is always exposed to external environment and intestinal microorganism; thus it is more sensitive to dysfunction and dysbiosis, leading to intestinal inflammation, such as inflammatory bowel disease (IBD), irritable bowel syndrome (IBS), and diarrhea. An increasing number of studies indicate that dietary amino acids play significant roles in preventing and treating intestinal inflammation. The review aims to summarize the functions and signaling mechanisms of amino acids in intestinal inflammation. Amino acids, including essential amino acids (EAAs), conditionally essential amino acids (CEAAs), and nonessential amino acids (NEAAs), improve the functions of intestinal barrier and expressions of anti-inflammatory cytokines and tight junction proteins but decrease oxidative stress and the apoptosis of enterocytes as well as the expressions of proinflammatory cytokines in the intestinal inflammation. The functions of amino acids are associated with various signaling pathways, including mechanistic target of rapamycin (mTOR), inducible nitric oxide synthase (iNOS), calcium-sensing receptor (CaSR), nuclear factor-kappa-B (NF-κB), mitogen-activated protein kinase (MAPK), nuclear erythroid-related factor 2 (Nrf2), general controlled nonrepressed kinase 2 (GCN2), and angiotensin-converting enzyme 2 (ACE2).

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