A Novel Stilbene-Like Compound That Reduces Melanin through Inhibiting Melanocyte Differentiation and Proliferation without Inhibiting Tyrosinase

Cosmetic practices that use skin-lightening agents to obtain desired skin tones or treat pigment abnormalities have been popular worldwide. However, the molecular and cellular mechanisms of these agents are still largely unknown. Here we identified a family of compounds, with the lead compound named A11, that exhibited strong pigment reduction in developing zebrafish embryos. The pigment inhibition lasted for several days and is effective both before and after melanogenesis. By comparison with several known skin-lightening compounds, A11 appeared to be more potent and caused slower pigment recovery after withdrawal. A11, however, did not inhibit tyrosinase or cause apoptosis in melanocytes. We further found that A11 suppressed proliferation in melanocytes and reduced the number of differentiated melanocytes by activating MAPK (mitogen-activated protein kinase) and Akt. Finally, A11 also caused melanin reduction in mammalian melanocytes. Together, A11 might be a potent skin-lightening agent with novel mechanisms.

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A Role for p38 Mitogen-Activated Protein Kinase in the Regulation of the Serotonin Transporter: Evidence for Distinct Cellular Mechanisms Involved in Transporter Surface Expression

Journal of Neuroscience ◽

10.1523/jneurosci.3754-04.2005 ◽

2005 ◽

Vol 25 (1) ◽

pp. 29-41 ◽

Cited By ~ 148

Author(s):

D. J. Samuvel

Keyword(s):

Protein Kinase ◽

Serotonin Transporter ◽

Surface Expression ◽

Mitogen Activated Protein Kinase ◽

Cellular Mechanisms ◽

Mitogen Activated Protein

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Gi-Coupled Receptor Activation Potentiates Piezo2 Currents via Gβγ

10.1101/722637 ◽

2019 ◽

Author(s):

John Smith Del Rosario ◽

Yevgen Yudin ◽

Songxue Su ◽

Cassandra Hartle ◽

Tooraj Mirshahi ◽

...

Keyword(s):

Protein Kinase ◽

Dorsal Root Ganglion ◽

Dorsal Root ◽

Mechanical Allodynia ◽

Receptor Activation ◽

Mitogen Activated Protein Kinase ◽

Drg Neurons ◽

Cellular Mechanisms ◽

Mitogen Activated Protein ◽

Phosphoinositide 3 Kinase

SUMMARYDysregulation of mechanosensitive Piezo2 channels is a hallmark of mechanical allodynia, yet the cellular mechanisms that sensitize mechanoreceptors are still poorly understood. Activation of Gi-coupled receptors sensitizes Piezo2 currents, but whether Gi-coupled receptors regulate the activity of Piezo2 channels is not known. Here, we found that activation of Gi-coupled receptors potentiates Piezo2 currents in dorsal root ganglion (DRG) neurons and in heterologous systems, but inhibits Piezo1 currents in heterologous systems. The potentiation, or inhibition of Piezo currents is abolished when blocking Gβγ with the c-terminal domain of the beta-adrenergic kinase (βARKct). Pharmacological inhibition of kinases downstream of Gβγ, phosphoinositide 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK), also abolished the potentiation of Piezo2 currents. Hence, our studies illustrate an indirect mechanism of action of Gβγ to sensitize Piezo2 currents after activation of Gi-coupled receptors.

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Analysis of Cells Proliferation and MicroRNAs Expression Profile in Human Chondrosarcoma SW1353 Cells Exposed to Iodine-125 Seeds Irradiation

Dose-Response ◽

10.1177/1559325820920525 ◽

2020 ◽

Vol 18 (2) ◽

pp. 155932582092052

Author(s):

Fusheng Li ◽

Jia Xu ◽

Yue Zhu ◽

Liang Sun ◽

Renyi Zhou

Keyword(s):

Cell Proliferation ◽

Protein Kinase ◽

Target Genes ◽

Mitogen Activated Protein Kinase ◽

Human Chondrosarcoma ◽

Before And After ◽

Mitogen Activated Protein ◽

Seed Irradiation ◽

Iodine 125

Chondrosarcoma is the second most common bone malignancy in adults, and it is often resistant to traditional chemotherapy and radiation therapy. Permanent implantation of iodine-125 (125I) seeds has been explored for the treatment of many types of cancer. In this study, the aim was to investigate the proliferative and microRNA (miRNA) effects of 125I seeds irradiation on human chondrosarcoma SW1353 cells. First, a new in vitro 125I seed irradiation model was established, and cell viability and miRNA microarray assays were performed before and after exposure to the 125I seeds. Cell proliferation was inhibited, and miRNA expression was substantially altered by irradiation exposure. The inhibition of cell proliferation was positively correlated with increased radiation doses, with cells showing the highest total radiation dose 7 days after irradiation. A total of 2549 miRNAs were detected in the SW1353 cells after exposure to 6 Gy of radiation, which included 189 differentially expressed miRNAs (98 upregulated and 91 downregulated). Four miRNAs were found to play important roles in the inhibition of cell proliferation after irradiation exposure, including miR-1224-5p, miR-492, miR-135b-5p, and miR-6839-5p. The target genes of the associated miRNAs mentioned were vascular endothelial growth factor A ( VEGFA), C-X-C motif chemokine 12 ( CXCL12), mitogen-activated protein kinase kinase kinase kinase 3 ( MAP4K3), and apoptosis facilitator Bcl-2-like protein 14 ( BCL2L14). Hence, the mitogen-activated protein kinase signaling pathway may be involved in how chondrosarcoma cells respond to 125I seed irradiation.

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Shp2–Mitogen-Activated Protein Kinase Signaling Drives Proliferation during Zebrafish Embryo Caudal Fin Fold Regeneration

Molecular and Cellular Biology ◽

10.1128/mcb.00515-17 ◽

2017 ◽

Vol 38 (4) ◽

Cited By ~ 1

Author(s):

Alexander James Hale ◽

Jeroen den Hertog

Keyword(s):

Cell Proliferation ◽

Catalytic Activity ◽

Protein Kinase ◽

Zebrafish Embryo ◽

Mapk Signaling ◽

Mitogen Activated Protein Kinase ◽

Zebrafish Embryos ◽

Caudal Fin ◽

Mitogen Activated Protein ◽

Wound Epidermis

ABSTRACT Regeneration of the zebrafish caudal fin following amputation occurs through wound healing, followed by formation of a blastema, which produces cells to replace the lost tissue in the final phase of regenerative outgrowth. We show that ptpn11a −/− ptpn11b −/− zebrafish embryos, lacking functional Shp2, fail to regenerate their caudal fin folds. Rescue experiments indicated that Shp2a has a functional signaling role, requiring its catalytic activity and SH2 domains but not the two C-terminal tyrosine phosphorylation sites. Surprisingly, expression of Shp2a variants with increased and reduced catalytic activity, respectively, rescued caudal fin fold regeneration to similar extents. Expression of mmp9 and junbb , indicative of formation of the wound epidermis and distal blastema, respectively, suggested that these processes occurred in ptpn11a −/− ptpn11b −/− zebrafish embryos. However, cell proliferation and MAPK phosphorylation were reduced. Pharmacological inhibition of MEK1 in wild-type zebrafish embryos phenocopied loss of Shp2. Our results suggest an essential role for Shp2a–mitogen-activated protein kinase (MAPK) signaling in promoting cell proliferation during zebrafish embryo caudal fin fold regeneration.

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