scholarly journals Anti-Melanogenic Effect of Chestnut Spike Extract through Downregulation of Tyrosinase-Related Proteins and Activation of ERK 1/2

2018 ◽  
Vol 13 (8) ◽  
pp. 1934578X1801300
Author(s):  
Jung-Hee Byeon ◽  
Md Badrul Alam ◽  
Ki-Chan Kim ◽  
Sangsun Heo ◽  
Ji-young Lim ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Phenotypic Trait ◽  
Dependent Manner ◽  
Melanin Content ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Key Factor ◽  
Related Proteins ◽  
Dose Dependent ◽  
Mitf Expression

Melanin has been reported to be the key factor for skin homeostasis. Besides defining an important human phenotypic trait, melanin overproduction may cause various disorders such as vitiligo, Addison's disease, Cushing's syndrome, and melasma. In this study, we aimed to investigate the anti-melanogenic potential of dried spike extract of chestnut. The extract inhibited tyrosinase (TYR) activity in a dose-dependent manner. Cellular melanin content decreased markedly after treatment with the extract. The spike extract inhibited microphthalmia-associated transcription factor (MITF) expression and downregulated TYR, TYRP-1, and TYRP-2 protein expression by increasing the phosphorylation of extracellular signal-regulated kinase (ERK)1/2 signalling pathway in melan-a cells. In addition, treatment with U0126, a specific inhibitor of ERK, restored melanin content. Collectively, these results suggest that the chestnut spike extract attenuated melanogenesis by inhibiting MITF expression and downregulating TYR, TYRP-1, and TYRP-2 protein expressions via activation of ERK1/2 pathway.

Involvement of the extracellular signal-regulated kinase 1/2 signaling pathway in amylin's eating inhibitory effect

2012 ◽  
Vol 302 (3) ◽  
pp. R340-R351 ◽  
Author(s):  
Catarina Soares Potes ◽  
Christina Neuner Boyle ◽  
Peter John Wookey ◽  
Thomas Riediger ◽  
Thomas Alexander Lutz
Keyword(s):  
Area Postrema ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Neuronal Responses ◽  
Extracellular Signal Regulated Kinase ◽  
Erk Phosphorylation ◽  
Extracellular Signal ◽  
Anorectic Effect ◽  
Feeding Trials ◽  
Dose Dependent

Peripheral amylin inhibits eating via the area postrema (AP). Because amylin activates the extracellular-signal regulated kinase 1/2 (ERK) pathway in some tissues, and because ERK1/2 phosphorylation (pERK) leads to acute neuronal responses, we postulated that it may be involved in amylin's eating inhibitory effect. Amylin-induced ERK phosphorylation (pERK) was investigated by immunohistochemistry in brain sections containing the AP. pERK-positive AP neurons were double-stained for the calcitonin 1a/b receptor, which is part of the functional amylin-receptor. AP sections were also phenotyped using dopamine-β-hydroxylase (DBH) as a marker of noradrenergic neurons. The effect of fourth ventricular administration of the ERK cascade blocker U0126 on amylin's eating inhibitory action was tested in feeding trials. The number of pERK-positive neurons in the AP was highest ∼10–15 min after amylin treatment; the effect appeared to be dose-dependent (5–20 μg/kg amylin). A portion of pERK-positive neurons in the AP carried the amylin-receptor and 22% of the pERK-positive neurons were noradrenergic. Pretreatment of rats with U0126 decreased the number of pERK-positive neurons in the AP after amylin injection. U0126 also attenuated the ability of amylin to reduce eating, at least when the animals had been fasted 24 h prior to the feeding trial. Overall, our results suggest that amylin directly stimulates pERK in AP neurons in a time- and dose-dependent manner. Part of the AP neurons displaying pERK were noradrenergic. At least under fasting conditions, pERK was shown to be a necessary part in the signaling cascade mediating amylin's anorectic effect.

scholarly journals Tropisetron Protects Against Acetaminophen-Induced Liver Injury via Suppressing Hepatic Oxidative Stress and Modulating the Activation of JNK/ERK MAPK Pathways

2016 ◽  
Vol 2016 ◽  
pp. 1-9 ◽  
Author(s):  
Fu-Chao Liu ◽  
Hung-Chen Lee ◽  
Chia-Chih Liao ◽  
Allen H. Li ◽  
Huang-Ping Yu
Keyword(s):  
Liver Injury ◽  
Map Kinases ◽  
Dependent Manner ◽  
Protective Effects ◽  
Mice Model ◽  
Terminal Protein ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Hepatic Lipid Peroxidation ◽  
Dose Dependent

Objectives. To investigate the protective effects of tropisetron on acetaminophen- (APAP-) induced liver injury in a mice model.Methods. C57BL/6 male mice were given tropisetron (0.3 to 10 mg/kg) 30 minutes before a hepatotoxic dose of acetaminophen (300 mg/kg) intraperitoneally. Twenty hours after APAP intoxication, sera alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels, hepatic myeloperoxidase (MPO), malondialdehyde (MDA), glutathione (GSH), and superoxide dismutase (SOD) activities, and liver histopathological changes were examined. The MAP kinases were also detected by western blotting.Results. Our results showed that tropisetron pretreatment significantly attenuated the acute elevations of the liver enzyme ALT level, hepatic MPO activity, and hepatocytes necrosis in a dose-dependent manner (0.3–10 mg/kg) in APAP-induced hepatotoxicity mice. Tropisetron (1 and 3 mg/kg) suppressed APAP-induced hepatic lipid peroxidation expression and alleviated GSH and SOD depletion. Administration of tropisetron also attenuated the phosphorylation of c-Jun-NH2-terminal protein kinase (JNK) and extracellular signal-regulated kinase (ERK) caused by APAP.Conclusion. Our data demonstrated that tropisetron’s hepatoprotective effect was in part correlated with the antioxidant, which were mediated via JNK and ERK pathways on acetaminophen-induced liver injury in mice.

scholarly journals Almost nontoxic tetrodotoxin analog, 5,6,11-trideoxytetrodotoxin, as an olfactory chemoattractant for the grass puffer

2021 ◽  
Author(s):  
Yasuhisa Noguchi ◽  
Takehisa Suzuki ◽  
Keigo Matsutani ◽  
Ryota Nakahigashi ◽  
Yoshiki Satake ◽  
...  
Keyword(s):  
Sensory Neurons ◽  
Olfactory Sensory Neurons ◽  
Dependent Manner ◽  
Behavioral Experiments ◽  
Extracellular Signal Regulated Kinase ◽  
Behavioral Studies ◽  
Defense Substance ◽  
Extracellular Signal ◽  
Dose Dependent ◽  
Fluorescent Dextran

Toxic puffers contain the potent neurotoxin, tetrodotoxin (TTX). Although TTX is considered to serve as a defense substance, previous behavioral studies have demonstrated that TTX (extracted from the ovary) acts as an attractive pheromone for some toxic puffers. To determine the putative pheromonal action of TTX, we examined whether grass puffers (Takifugu alboplumbeus) can detect TTX using electrophysiological, morphological, and behavioral experiments. Electroolfactogram results suggest that the olfactory epithelium of grass puffers responded in a dose-dependent manner to a type of TTX analog (5,6,11-trideoxyTTX), although it did not respond to TTX. We also examined the attractive action of 5,6,11-trideoxyTTX on grass puffers by recording their swimming behavior under dark conditions. Grass puffers preferred to stay on the side of the aquarium where 5,6,11-trideoxyTTX was administered, and their swimming speed decreased. Additionally, odorant-induced labeling of olfactory sensory neurons using a fluorescent dextran conjugate or immunohistochemistry against phosphorylated extracellular signal regulated kinase (pERK) revealed that labeled olfactory sensory neurons were localized in the region surrounding "islets" where there was abundant cilia on the olfactory lamella. 5,6,11-trideoxyTTX has been known to accumulate in grass puffers, but its toxicity is much lower (almost nontoxic) than TTX. Our results suggest that grass puffers can detect 5,6,11-trideoxyTTX using their nose and may positively use this functionally unknown TTX analog as an olfactory chemoattractant.

scholarly journals Inhibitory Effect of Arctigenin from Fructus Arctii Extract on Melanin Synthesis via Repression of Tyrosinase Expression

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Hwayong Park ◽  
Kwang Hoon Song ◽  
Pil Mun Jung ◽  
Ji-Eun Kim ◽  
Hyunju Ro ◽  
...  
Keyword(s):  
Active Compound ◽  
Gene Promoter ◽  
Inhibitory Effect ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Melanin Content ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal

To identify the active compound arctigenin in Fructus Arctii (dried seed of medicinal plantArctium lappa) and to elucidate the inhibitory mechanism in melanogenesis, we analyzed melanin content and tyrosinase activity on B16BL6 murine melanoma and melan-A cell cultures. Water extracts of Fructus Arctii were shown to inhibit tyrosinase activity in vitro and melanin content inα-melanocyte stimulating hormone-stimulated cells to similar levels as the well-known kojic acid and arbutin, respectively. The active compound arctigenin of Fructus Arctii displayed little or no cytotoxicity at all concentrations examined and decreased the relative melanin content and tyrosinase activity in a dose-dependent manner. Melanogenic inhibitory activity was also identified in vivo with zebrafish embryo. To determine the mechanism of inhibition, the effects of arctigenin on tyrosinase gene expression and tyrosinase promoter activity were examined. Also in addition, in the signaling cascade, arctigenin dose dependently decreased the cAMP level and promoted the phosphorylation of extracellular signal-regulated kinase. This result suggests that arctigenin downregulates cAMP and the tyrosinase enzyme through its gene promoter and subsequently upregulates extracellular signal-regulated kinase activity by increasing phosphorylation in the melanogenesis signaling pathway, which leads to a lower melanin content.

Curcumin Induces Cross-Regulation Between Autophagy and Apoptosis in Uterine Leiomyosarcoma Cells

2013 ◽  
Vol 23 (5) ◽  
pp. 803-808 ◽  
Author(s):  
Bin Li ◽  
Takashi Takeda ◽  
Kenji Tsuiji ◽  
Tze Fang Wong ◽  
Mari Tadakawa ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Western Blotting ◽  
Uterine Leiomyosarcoma ◽  
Dependent Manner ◽  
Inhibitory Effects ◽  
Extracellular Signal Regulated Kinase ◽  
Sequestosome 1 ◽  
Extracellular Signal ◽  
Experimental Findings ◽  
Dose Dependent

ObjectiveUterine leiomyosarcoma (LMS) has an unfavorable response to standard chemotherapy. A natural occurring compound, curcumin, has been shown to have inhibitory effects on cancers. We previously demonstrated that curcumin reduced uterine LMS cell proliferation by targeting the AKT-mTOR pathway and activating apoptosis. To further explore the anticancer effect of curcumin, we investigated the efficacy of curcumin on autophagy in LMS cells.MethodsCell proliferation in human uterine LMS cell lines, SKN and SK-UT-1, was assessed after exposure to rapamycin or curcumin. Autophagy was detected by Western blotting for light chain 3 and sequestosome 1 (SQSTM1/p62) expression. Apoptosis was confirmed by Western blotting for cleaved poly (ADP-ribose) polymerase (PARP).ResultsBoth rapamycin and curcumin potently inhibited SKN and SK-UT-1 cell proliferation in a dose-dependent manner. Curcumin induced autophagy and apoptosis in SKN and SK-UT-1 cells, whereas rapamycin, a specific mTOR inhibitor, did not. Curcumin increased extracellular signal-regulated kinase 1/2 activity in both SKN and SK-UT-1 cells, whereas PD98059, an MEK1 inhibitor, inhibited both the extracellular signal-regulated kinase 1/2 pathway and curcumin-induced autophagy.ConclusionsThese experimental findings suggest that curcumin is a potent inhibitor of cell proliferation in uterine LMS and provide new insights about ongoing signaling events leading to the possible development of a new therapeutic agent.

scholarly journals Tangeretin Triggers Melanogenesis through the Activation of Melanogenic Signaling Proteins and Sustained Extracellular Signal-Regulated Kinase in B16/F10 Murine Melanoma Cells

2015 ◽  
Vol 10 (3) ◽  
pp. 1934578X1501000 ◽  
Author(s):  
Hoon Seok Yoon ◽  
Hee-Chul Ko ◽  
Sang Suk Kim ◽  
Kyung Jin Park ◽  
Hyun Joo An ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Melanoma Cells ◽  
Response To Treatment ◽  
Signaling Proteins ◽  
Dependent Manner ◽  
Melanin Content ◽  
Extracellular Signal Regulated Kinase ◽  
Murine Melanoma ◽  
Extracellular Signal ◽  
Murine Melanoma Cells

In order to test the effectiveness of tangeretin at ameliorating melanoma and melanoma-associated depigmentation, western blotting was used to assess the melanin content of treated melanoma cells. Tangeretin, a 4′,5,6,7,8-pentamethoxyflavone, was found to trigger intracellular melanin production in a concentration-dependent manner in B16/F10 murine melanoma cells. Melanin content increased 1.74-fold in response to treatment with 25 μM of tangeretin, compared to that in non-treated cells. Examination of melanogenic protein expression showed that tyrosinase, tyrosinase-related protein (TRP)-1, and extracellular signal-regulated kinase (ERK) 1/2 levels increased in a dose-dependent manner. Furthermore, the expression of cyclic adenosine monophosphate response element binding protein (CREB) and microphthalmia transcription factor (MITF) was increased by tangeretin in 1 h and 4 h, respectively. Tangeretin-upregulated melanogenesis was suppressed by ERK 1/2 inhibitor and not by ERK1 inhibitor. These results suggest that tangeretin has therapeutic potential for melanoma and melanoma-associated depigmentation because it can induce hyperpigmentation through the activation of melanogenic signaling proteins and initiation of sustained ERK2 expression.

scholarly journals VEGF Mediates Retinal Müller Cell Viability and Neuroprotection through BDNF in Diabetes

Biomolecules ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 712
Author(s):  
Yun-Zheng Le ◽  
Bei Xu ◽  
Ana J. Chucair-Elliott ◽  
Huiru Zhang ◽  
Meili Zhu
Keyword(s):  
Specific Protein ◽  
Müller Cell ◽  
Dependent Manner ◽  
Vascular Abnormalities ◽  
Extracellular Signal ◽  
Muller Cell ◽  
Protein Kinase Akt ◽  
Sirna Knockdown ◽  
Endothelial Growth Factor ◽  
Dose Dependent

To investigate the mechanism of vascular endothelial growth factor (VEGF) and brain-derived neurotrophic factor (BDNF) in Müller cell (MC) viability and neuroprotection in diabetic retinopathy (DR), we examined the role of VEGF in MC viability and BDNF production, and the effect of BDNF on MC viability under diabetic conditions. Mouse primary MCs and cells of a rat MC line, rMC1, were used in investigating MC viability and BDNF production under diabetic conditions. VEGF-stimulated BDNF production was confirmed in mice. The mechanism of BDNF-mediated MC viability was examined using siRNA knockdown. Under diabetic conditions, recombinant VEGF (rVEGF) stimulated MC viability and BDNF production in a dose-dependent manner. rBDNF also supported MC viability in a dose-dependent manner. Targeting BDNF receptor tropomyosin receptor kinase B (TRK-B) with siRNA knockdown substantially downregulated the activated (phosphorylated) form of serine/threonine-specific protein kinase (AKT) and extracellular signal-regulated kinase (ERK), classical survival and proliferation mediators. Finally, the loss of MC viability in TrkB siRNA transfected cells under diabetic conditions was rescued by rBDNF. Our results provide direct evidence that VEGF is a positive regulator for BDNF production in diabetes for the first time. This information is essential for developing BDNF-mediated neuroprotection in DR and hypoxic retinal diseases, and for improving anti-VEGF treatment for these blood–retina barrier disorders, in which VEGF is a major therapeutic target for vascular abnormalities.

Abstract 10246: Hydroxychloroquine Pretreatment Reduces Myocardial Ischemia-Reperfusion Injury: Role of Cardiac Extracellular-Signal-Regulated Kinase 5 and Autophagy

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Feiyan Yang ◽  
Chang Yin ◽  
Lei Xi ◽  
Rakesh C Kukreja
Keyword(s):  
Infarct Size ◽  
Ischemia Reperfusion Injury ◽  
Myocardial Infarct ◽  
Ischemia Reperfusion ◽  
Beclin 1 ◽  
Myocardial Infarct Size ◽  
Western Blots ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Related Proteins

Background: Hydroxychloroquine (HCQ) is an antimalarial drug, which is also widely used to treat chronic rheumatologic diseases. Since HCQ was reported to inhibit cell autophagy and to activate extracellular-signal-regulated kinase 5 (ERK5) in vascular endothelial cells, we designed the current study to determine the effects of HCQ on cardiac ischemia-reperfusion (I-R) injury and post-I-R expression of ERK5 and autophagy marker proteins. Methods: Adult C57BL/6J mice of both genders were pretreated with HCQ (50 mg/kg, i.p.) 1 hour prior to isolation of the hearts, which were subjected to 30 min of no-flow global ischemia followed by 60 min of reperfusion in Langendorff mode. Ventricular function was continuously assessed and myocardial infarct size was determined at the end of I-R. Heart samples were collected following normoxic perfusion (no-ischemic controls), I-R, or I-R with HCQ for assessing ERK5 and autophagy-related proteins with Western blots. Results: HCQ pretreatment reduced infarct size significantly in the female hearts (P<0.05) as compared with the male hearts (Fig. A). Post-I-R cardiac function was better in HCQ-treated males (Fig. B). I-R resulted in a robust increase in total ERK5 (Fig. C) and phosphorylated ERK5 (Thr218/Tyr220) in both genders, which was abolished in HCQ-treated groups. Conversely, either I-R or HCQ did not affect the post-I-R cardiac expression of autophagy-related proteins (e.g., Atg5, Beclin-1, LC3II/LC3I ratio), except Beclin-1 phosphorylation was inhibited in HCQ-treated male hearts, but not females (Fig. D). Conclusions: Acute HCQ pretreatment affords cardioprotection against I-R injury in both genders. Interestingly, cardioprotective effects of HCQ are associated with a strong inhibitory effect on the induction of ERK5 following I-R in the heart, indicating a novel molecular mechanism underlying the HCQ-induced cardioprotection. However, the cardioprotective dose of HCQ has no major impact on cardiac autophagy.

scholarly journals Biphasic Dose–Response Induced by PCB150 and PCB180 in HeLa Cells and Potential Molecular Mechanisms

Dose-Response ◽  
2020 ◽  
Vol 18 (1) ◽  
pp. 155932582091004
Author(s):  
Ainy Zehra ◽  
Muhammad Zaffar Hashmi ◽  
Abdul Majid Khan ◽  
Tariq Malik ◽  
Zaigham Abbas
Keyword(s):  
Hela Cells ◽  
Molecular Mechanisms ◽  
Dependent Manner ◽  
Genotoxic Effects ◽  
Species Formation ◽  
Low Concentrations ◽  
Extracellular Signal ◽  
High Concentrations ◽  
High Doses ◽  
Dose Dependent

The polychlorinated biphenyls (PCBs) are persistent and their dose-dependent toxicities studies are not well-established. In this study, cytotoxic and genotoxic effects of PCB150 and PCB180 in HeLa cells were studied. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay indicated that the cell proliferation was stimulated at low doses (10−3 and 10−2 µg/mL for 12, 24, 48, and 72 hours) and inhibited at high doses (10 and 15 µg/mL for 24, 48, and 72 hours) for both PCBs. Increase in reactive oxygen species formation was observed in the HeLa cells in a time- and dose-dependent manner. Malondialdehyde and superoxide dismutase showed increased levels at high concentrations of PCBs over the time. Glutathione peroxidase expression was downregulated after PCBs exposure, suggested that both PCB congeners may attributable to cytotoxicity. Comet assay elicited a significant increase in genotoxicity at high concentrations of PCBs as compared to low concentrations indicating genotoxic effects. PCB150 and PCB180 showed decrease in the activity of extracellular signal–regulated kinase 1/2 and c-Jun N-terminal kinase at high concentrations after 12 and 48 hours. These findings may contribute to understanding the mechanism of PCBs-induced toxicity, thereby improving the risk assessment of toxic compounds in humans.

scholarly journals Purification and some properties of the 45 kDa diphenylene iodonium-binding flavoprotein of neutrophil NADPH oxidase

1990 ◽  
Vol 265 (1) ◽  
pp. 95-100 ◽  
Author(s):  
C M Yea ◽  
A R Cross ◽  
O T G Jones
Keyword(s):  
Polyclonal Antibodies ◽  
Specific Inhibitor ◽  
Small Subunit ◽  
Dependent Manner ◽  
Superoxide Generation ◽  
Diaphorase Activity ◽  
Low Concentrations ◽  
Diphenylene Iodonium ◽  
Neutrophil Superoxide ◽  
Dose Dependent

The 45 kDa diphenylene iodonium-binding flavoprotein of the human neutrophil superoxide-generating oxidase has been purified by affinity chromatography. The polypeptide was eluted from Blue Memsep or 2′,5′-ADP-agarose columns with either NADP or low concentrations of the specific inhibitor diphenylene iodonium. The purified protein was shown to bind FAD at a ratio of 1.09 mol of FAD/mol of protein. The reconstituted flavoprotein had a fluorescence spectrum similar, but not identical, to that of free FAD. It had an isoelectric point of approx. 4.0. The reconstituted flavoprotein displayed no diaphorase activity towards a range of artificial electron acceptors. Polyclonal antibodies raised against the pure protein inhibited superoxide generation by solubilized oxidase in a dose-dependent manner, and inhibited superoxide generation when incubated with either cytosol or membrane fractions in a reconstituted system. These antibodies precipitated the 45 kDa polypeptide together with a haem-containing 23 kDa protein thought to be the small subunit of cytochrome b-245. Antibodies raised against cytochrome P-450 reductase also precipitated these two polypeptides. These results are consistent with the 45 kDa polypeptide being the flavoprotein of the neutrophil superoxide-generating oxidase.

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