Quercetin suppresses the chymotrypsin-like activity of proteasome via inhibition of MEK1/ERK1/2 signaling pathway in hepatocellular carcinoma HepG2 cells

2018 ◽  
Vol 96 (5) ◽  
pp. 521-526 ◽  
Author(s):  
Youming Ding ◽  
Xiaoyan Chen ◽  
Bin Wang ◽  
Bin Yu ◽  
Jianhui Ge ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
P38 Mapk ◽  
Protease Activity ◽  
Molecular Mechanisms ◽  
Inhibitory Effect ◽  
Proteasome Activity ◽  
Flavonoid Compound ◽  
Jnk Signaling ◽  
Promising Target ◽  
Jnk Signaling Pathway

The proteasomal system is a promising target for cancer treatment. Quercetin (Que), a flavonoid compound with antitumor ability, displays the inhibitory effect on proteasome activity. However, the underlying molecular mechanisms are ill defined. The present study found that Que treatment significantly reduced the chymotrypsin-like protease activity of proteasome whereas the trypsin- and caspase-like protease activities remained unchanged in HepG2 cancer cells, along with activation of p38 MAPK and JNK and reduction of ERK1/2 phosphorylation. Que-reduced proteasome activity could not be reverted by inhibition of p38 MAPK and JNK signaling pathway. In addition, MEK1 overexpression or knockdown upregulated or downregulated the chymotrypsin-like protease activity of proteasome, respectively. Both Que and MEK1/ERK1/2 inhibitor attenuated the expression levels of proteasome β subunits. These results indicate that Que-induced suppression of MEK1/ERK1/2 signaling and subsequent reduction of proteasome β subunits is responsible for its inhibitory impacts on proteasome activity.

scholarly journals Terminal differentiation of human granulosa cells as luteinization is reversed by activin-A through silencing of Jnk pathway

2020 ◽  
Vol 6 (1) ◽  
Author(s):  
Gamze Bildik ◽  
Nazli Akin ◽  
Yashar Esmaeilian ◽  
Francesko Hela ◽  
Ceren Sultan Yildiz ◽  
...  
Keyword(s):  
Corpus Luteum ◽  
Signaling Pathway ◽  
Granulosa Cells ◽  
Molecular Mechanisms ◽  
Terminal Differentiation ◽  
Reproductive Technologies ◽  
Activin A ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Abstract Molecular mechanisms underlying luteinization (terminal differentiation of granulosa and theca cells after ovulation) and luteolysis (demise of corpus luteum) are poorly understood in human ovary. Here we report that activin-A, after binding to its cognate receptors induces a functional luteolytic state and reverses luteinization phenotype by downregulating the expression of the steroidogenic enzymes, LH receptor and VEGF and reducing estradiol (E2) progesterone (P4) production and upregulating FSH receptor and cyclin D1 expression in human primary luteinized granulosa cells. Further, this action of activin-A involves downregulation of JNK signaling pathway and is opposite to that of human chorionic gonadotropin (hCG), which acts as a luteotropic hormone and improves luteal function through the activation of JNK pathway in the same cell type. Reversal of luteinization phenotype in luteal granulosa cells by activin-A potentially makes this hormone an attractive candidate for use under certain clinical situations, where induction of luteolysis and rapid reduction of endogenous sex steroid levels are beneficial such as ovarian hyperstimulation syndrome (OHSS), in which the ovaries hyper-respond to gonadotropin stimulation by producing too many growing follicles along with development of ascites, pleural effusion, and hemo-concentrations as a result of increased vascular permeability and leakage of intravascular volume into third spaces. Our work unveils a previously undefined role for activin-A and JNK signaling pathway in human corpus luteum biology, that might have a direct clinical impact in assisted reproductive technologies.

scholarly journals XEDAR inhibits the proliferation and induces apoptosis of gastric cancer cells by regulating JNK signaling pathway

2019 ◽  
Vol 39 (12) ◽  
Author(s):  
Lihong Yang ◽  
Xiaojun Huang ◽  
Wei Wang ◽  
Tao Jiang ◽  
Feifei Ding
Keyword(s):  
Gastric Cancer ◽  
Cell Proliferation ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Gastric Cancer Cells ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway ◽  
Induced Apoptosis ◽  
Cancer Tissues

Abstract X-linked ectodermal dysplasia receptor (XEDAR) has been widely studied in epidermal morphogenesis, but few studies have been conducted on tumorigenesis and development, including gastric cancer. In the present research, we aimed to investigate the effect of XEDAR on gastric cancer and further explore the molecular mechanisms involved. The differential expression of XEDAR in 90 tissue specimens (30 gastric cancer tissues, 30 adjacent tissues and 30 normal tissues) was detected by real-time PCR (RT-PCR) and Western blot. Cell proliferation and apoptosis were explored using MTT and Annexin-V/propidium iodide (PI) assays, respectively. The results revealed that the expression of XEDAR was decreased in gastric cancer tissues and in gastric cancer cell lines, and its expression is regulated by p53 in BGC-823 cells. Furthermore, overexpression of XEDAR inhibited cell proliferation and induced apoptosis in BGC-823 cells. XEDAR moreover inhibited proliferation and induced apoptosis in gastric cancer cells by regulating the JNK signaling pathway. Collectively, the results of the present study suggested that XEDAR inhibits cell proliferation and induces apoptosis by participating in p53-mediated signaling pathway and inhibiting the downstream JNK signaling pathway in gastric cancer.

scholarly journals Dexmedetomidine Ameliorates Acute Stress-Induced Kidney Injury by Attenuating Oxidative Stress and Apoptosis through Inhibition of the ROS/JNK Signaling Pathway

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Yongping Chen ◽  
Xiujing Feng ◽  
Xueyuan Hu ◽  
Jichen Sha ◽  
Bei Li ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Molecular Mechanisms ◽  
Caspase 3 ◽  
Acute Stress ◽  
Death Receptor ◽  
Kidney Injury ◽  
Jnk Pathway ◽  
Jnk Signaling ◽  
Jnk Signaling Pathway

Acute stress induces tissue damage through excessive oxidative stress. Dexmedetomidine (DEX) reportedly has an antioxidant effect. However, protective roles and related potential molecular mechanisms of DEX against kidney injury induced by acute stress are unknown. Herein, rats were forced to swim 15 min followed by restraint stress for 3 h with/without DEX (30 μg/kg). Successful model establishment was validated by an open-field test. Assessment of renal function (creatinine, urea nitrogen), histopathology, oxidative stress (malondialdehyde, glutathione, and superoxide dismutase), and apoptosis (transferase-mediated dUTP nick end labeling) was performed. Localization of apoptosis was determined by immunohistochemistry of cleaved caspase 3 protein. In addition, key proteins of the death receptor-mediated pathway, mitochondrial pathway, endoplasmic reticulum stress (ERS) pathway, and ROS/JNK signaling pathway were measured by Western blot. We found that DEX significantly improved renal dysfunction, ameliorated kidney injury, reduced oxidative stress, and alleviated apoptosis. DEX also inhibited the release of norepinephrine (NE), decreased the production of reactive oxygen species (ROS), and inhibited JNK phosphorylation. Additionally, DEX downregulated the expression of Bax, cytochrome C, cleaved caspase 9, and cleaved caspase 3 proteins in mitochondria-dependent pathways. In summary, DEX protects against acute stress-induced kidney injury in rats by reducing oxidative stress and apoptosis via inhibition of the ROS/JNK pathway.

scholarly journals Transactivation of Naturally Occurring HIV-1 Long Terminal Repeats by the JNK Signaling Pathway

2000 ◽  
Vol 275 (27) ◽  
pp. 20382-20390 ◽  
Author(s):  
Peifeng Chen ◽  
Egbert Flory ◽  
Andris Avots ◽  
Bruce W. M. Jordan ◽  
Frank Kirchhoff ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Long Terminal Repeats ◽  
Jnk Signaling ◽  
Naturally Occurring ◽  
Jnk Signaling Pathway ◽  
Terminal Repeats ◽  
Hiv 1
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