Activation of mitogen-activated protein kinases/extracellular signal-regulated kinases in human hepatocellular carcinoma

Hepatology ◽  
1998 ◽  
Vol 27 (4) ◽  
pp. 951-958 ◽  
Author(s):  
Yoshiki Ito ◽  
Yutaka Sasaki ◽  
Masayoshi Horimoto ◽  
Shigeo Wada ◽  
Yoshio Tanaka ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Protein Kinases ◽  
Human Hepatocellular Carcinoma ◽  
Mitogen Activated Protein Kinases ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

scholarly journals Roles of Mitogen-Activated Protein Kinases in Osteoclast Biology

2018 ◽  
Vol 19 (10) ◽  
pp. 3004 ◽  
Author(s):  
Kyunghee Lee ◽  
Incheol Seo ◽  
Mun Choi ◽  
Daewon Jeong
Keyword(s):  
Bone Resorption ◽  
Protein Kinases ◽  
Current Knowledge ◽  
Osteoclast Differentiation ◽  
Cathepsin K ◽  
Proton Pumping ◽  
Mitogen Activated Protein Kinases ◽  
Extracellular Signal ◽  
Mitogen Activated Protein ◽  
Inorganic Mineral

Bone undergoes continuous remodeling, which is homeostatically regulated by concerted communication between bone-forming osteoblasts and bone-degrading osteoclasts. Multinucleated giant osteoclasts are the only specialized cells that degrade or resorb the organic and inorganic bone components. They secrete proteases (e.g., cathepsin K) that degrade the organic collagenous matrix and establish localized acidosis at the bone-resorbing site through proton-pumping to facilitate the dissolution of inorganic mineral. Osteoporosis, the most common bone disease, is caused by excessive bone resorption, highlighting the crucial role of osteoclasts in intact bone remodeling. Signaling mediated by mitogen-activated protein kinases (MAPKs), including extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38, has been recognized to be critical for normal osteoclast differentiation and activation. Various exogenous (e.g., toll-like receptor agonists) and endogenous (e.g., growth factors and inflammatory cytokines) stimuli contribute to determining whether MAPKs positively or negatively regulate osteoclast adhesion, migration, fusion and survival, and osteoclastic bone resorption. In this review, we delineate the unique roles of MAPKs in osteoclast metabolism and provide an overview of the upstream regulators that activate or inhibit MAPKs and their downstream targets. Furthermore, we discuss the current knowledge about the differential kinetics of ERK, JNK, and p38, and the crosstalk between MAPKs in osteoclast metabolism.

scholarly journals Anti-Melanogenic Effects of Bergamottin via Mitogen-Activated Protein Kinases and Protein Kinase B Signaling Pathways

2019 ◽  
Vol 14 (7) ◽  
pp. 1934578X1986210
Author(s):  
You Chul Chung ◽  
Yun Beom Kim ◽  
Bong Seok Kim ◽  
Chang-Gu Hyun
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Protein Kinase B ◽  
Positive Control ◽  
Akt Inhibitor ◽  
Mitogen Activated Protein Kinases ◽  
Melanocyte Stimulating Hormone ◽  
B16f10 Cells ◽  
Extracellular Signal ◽  
Mitogen Activated Protein

In this study, we examined the inhibitory effects of bergamottin on melanogenesis in B16F10 murine melanoma cells, together with its effects on the mechanism of melanin synthesis. α-Melanocyte stimulating hormone-stimulated B16F10 cells were treated with various concentrations of bergamottin, with arbutin as a positive control. Bergamottin significantly decreased the melanin content and tyrosinase activity without showing any cytotoxicity. In addition, bergamottin treatment significantly downregulated the expression of tyrosinase-related protein-1,2 and tyrosinase by suppressing the expression of microphthalmia-associated transcription factor. The phosphorylation status of mitogen-activated protein kinases (MAPKs) and protein kinase B (AKT) was examined to determine the mechanism underlying the antimelanogenic effects of bergamottin. Bergamottin treatment increased the phosphorylation of extracellular signal-regulated kinase (ERK) and AKT, but decreased the phosphorylation of p38 and c-Jun N-terminal kinase in the B16F10 cells. Moreover, the use of PD98059 (ERK inhibitor) and LY294002 (AKT inhibitor) corroborated these findings, indicating that bergamottin inhibits melanogenesis via the MAPKase and AKT signaling pathway. Thus, bergamottin has potential for treating hyperpigmentation disorders and can be a promising chemical for skin-whitening in the cosmetic industry.

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