scholarly journals Ginsenosides Rb1 and Rg1 Stimulate Melanogenesis in Human Epidermal Melanocytes via PKA/CREB/MITF Signaling

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Mao Lin ◽  
Bao-Xiang Zhang ◽  
Ci Zhang ◽  
Nan Shen ◽  
Yun-Ying Zhang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Skin Pigmentation ◽  
Camp Response Element Binding ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Melanin Content ◽  
Protein Levels ◽  
Human Melanocytes ◽  
Element Binding Protein ◽  
Phosphorylated Creb

Reduced or defective melanin skin pigmentation may cause many hypopigmentation disorders and increase the risk of damage to the skin triggered by UV irradiation. Ginsenosides Rb1 and Rg1 have many molecular targets including the cAMP-response element-binding protein (CREB), which is involved in melanogenesis. This study aimed to investigate the effects of ginsenosides Rb1 and Rg1 on melanogenesis in human melanocytes and their related mechanisms. The effects of Rb1 and Rg1 on cell viability, tyrosinase activity, cellular melanin content and protein levels of tyrosinase, microphthalmia-associated transcription factor (MITF), and activation of CREB in melanocytes were assessed. Results showed that Rb1 or Rg1 significantly increased cellular melanin content and tyrosinase activity in a dose-dependent manner. By contrast, the cell viability of melanocytes remained unchanged. After exposure to Rb1 or Rg1, the protein levels of tyrosinase, MITF, and phosphorylated CREB were significantly increased. Furthermore, pretreatment with the selective PKA inhibitor H-89 significantly blocked the Rb1- or Rg1-induced increase of melanin content. These findings indicated that Rb1 and Rg1 increased melanogenesis and tyrosinase activity in human melanocytes, which was associated with activation of PKA/CREB/MITF signaling. The effects and mechanisms of Rb1 or Rg1 on skin pigmentation deserve further study.

scholarly journals Carvedilol, an Adrenergic Blocker, Suppresses Melanin Synthesis by Inhibiting the cAMP/CREB Signaling Pathway in Human Melanocytes and Ex Vivo Human Skin Culture

2020 ◽  
Vol 21 (22) ◽  
pp. 8796
Author(s):  
Myoung Eun Choi ◽  
Hanju Yoo ◽  
Ha-Ri Lee ◽  
Ik Joon Moon ◽  
Woo Jin Lee ◽  
...  
Keyword(s):  
Human Skin ◽  
Ex Vivo ◽  
Skin Pigmentation ◽  
Cyclic Adenosine Monophosphate ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Catecholamine Biosynthesis ◽  
Human Melanocytes ◽  
Adrenergic Blocker ◽  
Element Binding Protein

Catecholamines function via G protein-coupled receptors, triggering an increase in intracellular levels of 3′,5′-cyclic adenosine monophosphate (cAMP) in various cells. Catecholamine biosynthesis and the β-adrenergic receptor exist in melanocytes; thus, catecholamines may play critical roles in skin pigmentation. However, their action and mechanisms mediating melanogenesis in human skin have not yet been investigated. Therefore, we examined the potential anti-melanogenetic effect of carvedilol, a nonselective β-blocker with weak α1-blocking activities. Carvedilol reduced melanin content and cellular tyrosinase activity without compromising cellular viability in normal human melanocytes as well as in mel-Ab immortalized mouse melanocytes. Carvedilol downregulated microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase-related protein (TRP)-1, and TRP-2. Carvedilol treatment led to the downregulation of phosphor-cAMP response element-binding protein (CREB). Moreover, the increase in cAMP levels upon treatment with forskolin reversed the anti-melanogenic action of carvedilol. In addition, carvedilol remarkably reduced the melanin index in ultraviolet-irradiated human skin cultures. Taken together, our results indicate that carvedilol effectively suppresses melanogenesis in human melanocytes and ex vivo human skin by inhibiting cAMP/protein kinase A/CREB signaling. The anti-melanogenic effects of carvedilol have potential significance for skin whitening agents.

scholarly journals Acupuncture Activates ERK-CREB Pathway in Rats Exposed to Chronic Unpredictable Mild Stress

2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Jun Lu ◽  
Jia Liang ◽  
Jun-Ren Wang ◽  
Li Hu ◽  
Ya Tu ◽  
...  
Keyword(s):  
Camp Response Element Binding ◽  
Mild Stress ◽  
Chronic Unpredictable Mild Stress ◽  
Camp Response Element ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Phosphorylated Creb ◽  
The Brain ◽  
Creb Pathway

Extracellular signal-regulated kinase (ERK)-cAMP response element binding protein (CREB) signal pathway has been implicated in the pathogenesis of depression. There is growing evidence that acupuncture in traditional Chinese medicine has antidepressant-like effect. However, the effect of acupuncture on ERK-CREB pathway remains unknown. In our study, the antidepressant-like effect of acupuncture treatment was measured by sucrose intake test and open field test in rats exposed to chronic unpredictable mild stress (CUMS) for 4 weeks. The protein levels of ERK1/2, CREB, phosphorylated ERK1/2 (p-ERK1/2), and phosphorylated CREB (p-CREB) in the hippocampus (HP) and prefrontal cortex (PFC) were examined by Western blot analysis. Our results showed that CUMS rats exhibited the reduction in behavioral activities, whereas acupuncture stimulation at acupoints Baihui (Du20) and Neiguan (PC6) reversed the behavioral deficit. In addition, exposure to CUMS resulted in the decrease of p-ERK1/2 and p-CREB in the HP and PFC. Acupuncture increased the ratio of p-ERK1/2 to ERK1/2 and the ratio of p-CREB to CREB in the HP and PFC. Our study suggested that one potential way, by which acupuncture had antidepressant-like effect, might be mediated by activating the ERK-CREB pathway in the brain.

scholarly journals Melanogenesis Inhibitor(s) fromPhyla nodifloraExtract

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Feng-Lin Yen ◽  
Moo-Chin Wang ◽  
Chan-Jung Liang ◽  
Horng-Huey Ko ◽  
Chiang-Wen Lee
Keyword(s):  
Inflammatory Diseases ◽  
Folk Medicine ◽  
Camp Response Element Binding ◽  
Dependent Manner ◽  
Melanin Content ◽  
Camp Response Element ◽  
Alternative Medicines ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Element Binding Protein

Overexpression of tyrosinase can cause excessive production of melanin and lead to hyperpigmentation disorders, including melasma and freckles. Recently, agents obtained from plants are being used as alternative medicines to downregulate tyrosinase synthesis and decrease melanin production.Phyla nodifloraGreene (Verbenaceae) is used as a folk medicine in Taiwanese for treating and preventing inflammatory diseases such as hepatitis and dermatitis. However, the antimelanogenesis activity and molecular biological mechanism underlying the activity of the methanolic extract ofP. nodiflora(PNM) have not been investigated to date. Our results showed that PNM treatment was not cytotoxic and significantly reduced the cellular melanin content and tyrosinase activity in a dose-dependent manner (P<0.05). Further, PNM exhibited a significant antimelanogenesis effect (P<0.05) by reducing the levels of phospho-cAMP response element-binding protein and microphthalmia-associated transcription factor (MITF), inhibiting the synthesis of tyrosinase, tyrosinase-related protein-1 (TRP-1), and TRP-2, and decreasing the cellular melanin content. Moreover, PNM significantly activated the phosphorylation of mitogen-activated protein kinases, including phospho-extracellular signal-regulated kinase, c-Jun N-terminal kinase, and phospho-p38, and inhibited the synthesis of MITF, thus decreasing melanogenesis. These properties suggest that PNM could be used as a clinical and cosmetic skin-whitening agent to cure and/or prevent hyperpigmentation.

scholarly journals Effect of Purified Mushroom Tyrosinase on Melanin Content and Melanogenic Protein Expression

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Kamal Uddin Zaidi ◽  
Sharique A. Ali ◽  
Ayesha S. Ali
Keyword(s):  
Kinase Inhibitors ◽  
Pigment Cell ◽  
Adenosine Monophosphate ◽  
Camp Response Element Binding ◽  
Protein Kinase Inhibitors ◽  
Tyrosinase Activity ◽  
Dependent Manner ◽  
Mushroom Tyrosinase ◽  
Melanin Content ◽  
Dose Dependent

In mammalian melanocytes, melanosome is a highly specialized organelle where melanin is synthesized. Melanin synthesis is controlled by tyrosinase, the vital enzyme in melanogenic pathway. The present investigation is based on an effect of purified mushroom tyrosinase of Agaricus bisporus on B16F10 melanocytes for the melanin production via blocking pigment cell machinery. Using B16F10 melanocytes showed that the stimulation of melanogenesis by purified tyrosinase is due to increased tyrosinase absorption. Cellular tyrosinase activity and melanin content in B16F10 melanocytes were increased by purified tyrosinase in a dose-dependent manner. Western blot analysis revealed that cellular tyrosinase levels were enhanced after treatment with purified tyrosinase for 48 hours. Furthermore, tyrosinase induced phosphorylation of cyclic adenosine monophosphate (cAMP) response element-binding protein (CREB) in a dose-dependent manner. The purified tyrosinase-mediated increase of tyrosinase activity was significantly attenuated by H89, LY294002, Ro-32-0432, and PD98059, cAMP-dependent protein kinase inhibitors. The results indicate that purified tyrosinase can be used as contestant for the treatment of vitiligous skin conditions.

scholarly journals Estradiol Suppresses Phosphorylation of Cyclic Adenosine 3′,5′-Monophosphate Response Element Binding Protein (CREB) in the Pituitary: Evidence for Indirect Action via Gonadotropin-Releasing Hormone

1999 ◽  
Vol 13 (8) ◽  
pp. 1338-1352
Author(s):  
W. Rachel Duan ◽  
Jennifer L. Shin ◽  
J. Larry Jameson
Keyword(s):  
Gene Promoter ◽  
Camp Response Element Binding ◽  
Ovariectomized Rats ◽  
Pituitary Cells ◽  
Camp Response Element ◽  
Similar Reduction ◽  
Response Element ◽  
Creb Phosphorylation ◽  
Element Binding Protein ◽  
Phosphorylated Creb

Abstract Estradiol acts on the hypothalamus and pituitary gland to modulate the synthesis and secretion of gonadotropins. We recently reported that GnRH-induced transcription of the human gonadotropin α-gene promoter is increased markedly in transfected pituitary cells derived from animals treated with estradiol. Because the cAMP response element binding (CREB) protein plays an important role in the transcriptional regulation of this promoter and is highly regulated by posttranslational phosphorylation, we hypothesized that it might serve as a target for estradiol-induced sensitivity to GnRH. In this study, we assessed the roles of estradiol and GnRH in the regulation of CREB phosphorylation in the rat pituitary. Using an antibody that specifically recognizes phosphorylated CREB (pCREB), we found that the pituitary content of pCREB was inversely related to the level of estradiol during the estrous cycle. Ovariectomy increased the level of pCREB, and treatment with estradiol for 10 days decreased the content of pCREB dramatically (93% inhibition). A similar reduction of pCREB was seen when ovariectomized rats were treated with a GnRH receptor antagonist for 10 days. This result indicates that the ovariectomy-induced increase in pCREB is GnRH-dependent. In αT3 gonadotrope cells, estradiol had no direct effect on CREB phosphorylation, whereas GnRH increased CREB phosphorylation 4- to 5-fold within 5 min. We conclude that estradiol inhibits CREB phosphorylation in the gonadotrope, probably by inhibiting GnRH production. The estradiol-induced decrease in CREB phosphorylation is proposed to lower basalα -promoter activity and increase its responsiveness to GnRH. (Molecular Endocrinology 13: 1338–1352, 1999)

ACTH STIMULATES MELANOGENESIS IN CULTURED HUMAN MELANOCYTES

1994 ◽  
Vol 140 (1) ◽  
pp. R1-R3 ◽  
Author(s):  
G. Hunt ◽  
C. Todd ◽  
S. Kyne ◽  
A.J. Thody
Keyword(s):  
Dose Response ◽  
Plasma Levels ◽  
Culture System ◽  
Skin Pigmentation ◽  
Physiological Role ◽  
Melanin Content ◽  
Response Curves ◽  
Human Melanocytes ◽  
First Time ◽  
Rate Limiting

ABSTRACT While ACTH is known to induce skin pigmentation in man, its effects on cultured human melanocytes have not been investigated. Using a culture system free of artificial mitogens, we report for the first time that ACTH stimulates melanogenesis in cultured human melanocytes. While ACTH, α-MSH and the synthetic α-MSH analogue Nle4DPhe7α-MSH all stimulate the activity of tyrosinase, the rate limiting enzyme in melanogenesis, and all produce a 50% increase in the melanin content of the cells at a concentration of 10−8-10−7 mol/l, the shapes of the dose response curves differ: those for the MSH peptides are sigmoidal while those for ACTH are biphasic. In addition, human melanocytes are able to respond to concentrations of ACTH comparable with physiological plasma levels. We suggest that ACTH may be relatively more important than α-MSH as a pigmentary hormone in man and could have a physiological role in skin pigmentation.

scholarly journals Difluoromethylornithine Induces Apoptosis through Regulation of AP-1 Signaling via JNK Phosphorylation in Epithelial Ovarian Cancer

2021 ◽  
Vol 22 (19) ◽  
pp. 10255
Author(s):  
Woo Yeon Hwang ◽  
Wook Ha Park ◽  
Dong Hoon Suh ◽  
Kidong Kim ◽  
Yong Beom Kim ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cell Viability ◽  
Epithelial Ovarian Cancer ◽  
Cancer Cells ◽  
Ovarian Cancer Cells ◽  
Dependent Manner ◽  
Irreversible Inhibitor ◽  
Protein Levels ◽  
Bax Protein ◽  
Apoptotic Effects

Difluoromethylornithine (DFMO), an irreversible inhibitor of ornithine decarboxylase (ODC), has promising activity against various cancers and a tolerable safety profile for long-term use as a chemopreventive agent. However, the anti-tumor effects of DFMO in ovarian cancer cells have not been entirely understood. Our study aimed to identify the effects and mechanism of DFMO in epithelial ovarian cancer cells using SKOV-3 cells. Treatment with DFMO resulted in a significantly reduced cell viability in a time- and dose-dependent manner. DFMO treatment inhibited the activity and downregulated the expression of ODC in ovarian cancer cells. The reduction in cell viability was reversed using polyamines, suggesting that polyamine depletion plays an important role in the anti-tumor activity of DFMO. Additionally, significant changes in Bcl-2, Bcl-xL, Bax protein levels, activation of caspase-3, and cleavage of poly (ADP-ribose) polymerase were observed, indicating the apoptotic effects of DFMO. We also found that the effect of DFMO was mediated by AP-1 through the activation of upstream JNK via phosphorylation. Moreover, DFMO enhanced the effect of cisplatin, thus showing a possibility of a synergistic effect in treatment. In conclusion, treatment with DFMO alone, or in combination with cisplatin, could be a promising treatment for ovarian cancer.

Di-2-ethylhexyl phthalate (DEHP) induces apoptosis of mouse HT22 hippocampal neuronal cells via oxidative stress

2020 ◽  
Vol 36 (11) ◽  
pp. 844-851
Author(s):  
Wei Tu ◽  
Weifeng Li ◽  
Xingen Zhu ◽  
Linlin Xu
Keyword(s):  
Oxidative Stress ◽  
Cell Viability ◽  
Neuronal Cell ◽  
Underlying Mechanism ◽  
Treated Group ◽  
Dependent Manner ◽  
Ht22 Cells ◽  
Protein Levels ◽  
Ethylhexyl Phthalate

Di-2-ethylhexyl phthalate (DEHP) has been widely used as a plasticizer in industry and can affect memory; however, the underlying mechanism remains unclear. In the present study, mouse HT22 cells, an immortalized hippocampal neuronal cell line, was utilized as an in vitro model. We showed that DEHP dramatically inhibited cell viability and increased lactate dehydrogenase (LDH) release from the cells in a dose-dependent manner, suggesting that DEHP could cause cytotoxicity of mouse HT22 cells. The protein levels of cleaved Caspase-8, cleaved Caspase-3, and Bax markedly increased in the DEHP-treated cells, whereas there was a significant decrease in the Bcl-2 protein level, implying that DEHP could induce apoptosis of mouse HT22 cells. DEHP exposure significantly increased the content of malondialdehyde, whereas it markedly decreased the level of glutathione and the activities of glutathione peroxidase and superoxide dismutase, suggesting that DEHP induced oxidative stress of the cells. Compared with the DEHP-treated group, the inhibition of cell viability and the release of LDH were rescued in the N-acetyl-l-cysteine plus DEHP group. Furthermore, inhibition of oxidative stress could rescue the induction of apoptosis by DEHP. Collectively, our results indicated that DEHP could induce apoptosis of mouse HT22 cells via oxidative stress.

scholarly journals Minocycline Protects against Rotenone-Induced Neurotoxicity Correlating with Upregulation of Nurr1 in a Parkinson’s Disease Rat Model

2019 ◽  
Vol 2019 ◽  
pp. 1-7 ◽  
Author(s):  
Congcong Sun ◽  
Yun Wang ◽  
Mingshu Mo ◽  
Chengyuan Song ◽  
Xingbang Wang ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Rat Model ◽  
Camp Response Element Binding ◽  
Motor Deficits ◽  
Camp Response Element ◽  
Protein Levels ◽  
Immobility Time ◽  
Element Binding Protein ◽  
Commercial Kits

The aim of this study was to investigate the effect of minocycline in rats with rotenone-induced Parkinson’s disease (PD). The open field test was performed to determine the motor ability of the rats. Double immunofluorescence staining was used to detect the expression of tyrosine hydroxylase (TH) and Nurr1 in the substantia nigra (SN) of rats. The relative protein levels of TH, Nurr1, and the total- and phosphorylated-cAMP-response element binding protein (CREB) were determined by western blot analysis. The production of reactive oxygen species (ROS) and nitric oxide (NO) was detected by commercial kits. After exposure to rotenone for 28 days, rats exhibited decreased ambulation and rearing frequency and prolonged immobility time with loss of TH positive neurons in the SN. The phosphorylation levels of CREB and Nurr1 expression decreased significantly accompanied with the release of ROS and NO. Minocycline alleviated the motor deficits of rats lesioned by rotenone and elevated the expression of TH, as well as suppressing the release of ROS and NO in the SN. That was in line with the elevated phosphorylation levels of CREB and Nurr1 expression. In conclusion, our present study showed minocycline protected against neurotoxicity in a rotenone-induced rat model of PD, which was correlated with upregulation of Nurr1.

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