Zerumbone Reduces the Level of MAPK1 by Upregulating Mir-758-3p to Inhibit the Survival of Thyroid Papillary Cancer Cells

2020 ◽  
Vol 18 (4) ◽  
pp. 378-385
Author(s):  
Huling Wen ◽  
Zhengmin Xu ◽  
Dan Wen ◽  
Shiyu Lin ◽  
Yu Liang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Papillary Carcinoma ◽  
Lentiviral Vector ◽  
Therapeutic Potential ◽  
Thyroid Papillary Carcinoma ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Assay ◽  
Protective Effects ◽  
Thyroid Papillary ◽  
Mitogen Activated Protein

Thyroid papillary carcinoma is the most common type of thyroid malignancy. The mitogen-activated protein kinase signaling cascade is the major pathway involved in thyroid papillary carcinoma and may be regulated by small molecules and transcription factors. Zerumbone is a bioactive compound with multiple pharmacological properties. This study investigated the effects of zerumbone on survival and proliferation of thyroid papillary carcinoma-1 cells with an emphasis on the level of microRNA-758-3p and its target gene, mitogen-activated protein kinase-1. Zerumbone exhibited dose-dependent inhibitory effects on the viability and proliferation of thyroid papillary carcinoma-1 cells. It also gradually elevated the level of microRNA-758-3p but decreased mitogen-activated protein kinase-1 expression in these cells. Mitogen-activated protein kinase-1 has been suggested as a downstream target of microRNA-758-3p and confirmed by dual-reporter luciferase assay. The downregulation of microRNA-758-3p in thyroid papillary carcinoma-1 cells via the transfection with microRNA-758-3p inhibitor reversed the inhibitory effect of zerumbone on mitogen-activated protein kinase-1 expression. Furthermore, the transfection of thyroid papillary carcinoma-1 cells with lentiviral vector overexpressing mitogen-activated protein kinase-1 eliminated the protective effects of zerumbone on thyroid papillary carcinoma progression as compared to the group delivered with control vector. In conclusion, this study demonstrated that zerumbone inhibited survival and proliferation of thyroid papillary carcinoma-1 cells via suppressing the expression of mitogen-activated protein kinase-1 through microRNA-758-3p. These data suggest the therapeutic potential of zerumbone in thyroid papillary carcinoma treatment.

scholarly journals Ischemic Postconditioning as a Novel Avenue to Protect against Brain Injury after Stroke

2009 ◽  
Vol 29 (5) ◽  
pp. 873-885 ◽  
Author(s):  
Heng Zhao
Keyword(s):  
Protein Kinase ◽  
Reperfusion Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Ischemic Postconditioning ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Protective Mechanisms ◽  
Mitogen Activated Protein ◽  
Cerebral Ischemic

Ischemic postconditioning initially referred to a stuttering reperfusion performed immediately after reperfusion, for preventing ischemia/reperfusion injury in both myocardial and cerebral infarction. It has evolved into a concept that can be induced by a broad range of stimuli or triggers, and may even be performed as late as 6 h after focal ischemia and 2 days after transient global ischemia. The concept is thought to be derived from ischemic preconditioning or partial/gradual reperfusion, but in fact the first experiment for postconditioning was carried out much earlier than that of preconditioning or partial/gradual reperfusion, in the research on myocardial ischemia. This review first examines the protective effects and parameters of postconditioning in various cerebral ischemic models. Thereafter, it provides insights into the protective mechanisms of postconditioning associated with reperfusion injury and the Akt, mitogen-activated protein kinase (MAPK), protein kinase C (PKC), and ATP-sensitive K+ (KATP) channel cell signaling pathways. Finally, some open issues and future challenges regarding clinical translation of postconditioning are discussed.

scholarly journals Xanthohumol, a Prenylated Flavonoid from Hops (Humulus lupulus), Prevents Platelet Activation in Human Platelets

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Ye-Ming Lee ◽  
Kuo-Hsien Hsieh ◽  
Wan-Jung Lu ◽  
Hsiu-Chu Chou ◽  
Duen-Suey Chou ◽  
...  
Keyword(s):  
Platelet Aggregation ◽  
Protein Kinase ◽  
Platelet Activation ◽  
Therapeutic Potential ◽  
Inhibitory Effect ◽  
Human Platelets ◽  
Humulus Lupulus ◽  
Mitogen Activated Protein Kinase ◽  
Akt Phosphorylation ◽  
Mitogen Activated Protein

Xanthohumol is the principal prenylated flavonoid in the hop plant (Humulus lupulusL.). Xanthohumol was found to be a very potent cancer chemopreventive agent through regulation of diverse mechanisms. However, no data are available concerning the effects of xanthohumol on platelet activation. The aim of this paper was to examine the antiplatelet effect of xanthohumol in washed human platelets. In the present paper, xanthohumol exhibited more-potent activity in inhibiting platelet aggregation stimulated by collagen. Xanthohumol inhibited platelet activation accompanied by relative [Ca2+]imobilization, thromboxane A2formation, hydroxyl radical (OH●) formation, and phospholipase C (PLC)γ2, protein kinase C (PKC), mitogen-activated protein kinase (MAPK), and Akt phosphorylation. Neither SQ22536, an inhibitor of adenylate cyclase, nor ODQ, an inhibitor of guanylate cyclase, reversed the xanthohumol-mediated inhibitory effect on platelet aggregation. Furthermore, xanthohumol did not significantly increase nitrate formation in platelets. This study demonstrates for the first time that xanthohumol possesses potent antiplatelet activity which may initially inhibit the PI3-kinase/Akt, p38 MAPK, and PLCγ2-PKC cascades, followed by inhibition of the thromboxane A2formation, thereby leading to inhibition of [Ca2+]iand finally inhibition of platelet aggregation. Therefore, this novel role of xanthohumol may represent a high therapeutic potential for treatment or prevention of cardiovascular diseases.

scholarly journals Embelin as a Novel Inhibitor of PKC in the Prevention of Platelet Activation and Thrombus Formation

2019 ◽  
Vol 8 (10) ◽  
pp. 1724 ◽  
Author(s):  
Jiun Yi Li ◽  
Ray Jade Chen ◽  
Li Ting Huang ◽  
Tzu Yin Lee ◽  
Wan Jung Lu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Therapeutic Potential ◽  
Thrombus Formation ◽  
Biological Activities ◽  
Mitogen Activated Protein Kinase ◽  
Antitumor Effects ◽  
Pkc Inhibitor ◽  
Downstream Signaling ◽  
Embelia Ribes ◽  
Mitogen Activated Protein

Embelin is a quinone derivative and found in the fruits of Embelia ribes Burm.f. Embelin has been identified as a small molecular inhibitor of X-chromosome-linked inhibitor of apoptosis proteins, and has multiple biological activities, including antioxidation, anti-inflammation, and antitumor effects. However, the effect of embelin in platelets remains unclear. Thus, this study investigated the antiplatelet mechanism of embelin. Our data revealed that embelin could inhibit platelet aggregation induced by various agonists, including the protein kinase C (PKC) activator phorbol 12,13-dibutyrate (PDBu). Embelin, as well as the PKC inhibitor Ro 31-8220, markedly reduced PDBu-mediated phosphorylation of the PKC substrate, suggesting that embelin may be a PKC inhibitor for platelets. Embelin could block PKC downstream signaling and events, including the inhibition of protein kinase B and mitogen-activated protein kinase activation, granule release, and glycoprotein IIbIIIa activation. Moreover, embelin could delay thrombus formation in the mesenteric microvessels of mice, but did not significantly affect the tail bleeding time. In conclusion, we demonstrated that embelin is a PKC inhibitor and possesses antiplatelet and antithrombotic effects. The further analysis is necessary to more accurately determine clinical therapeutic potential of embelin in all clinical thromboembolic events with disturbance of thrombocyte function.

miR-666-3p mediates the protective effects of mesenchymal stem cell-derived exosomes against oxygen–glucose deprivation and reoxygenation-induced cell injury in brain microvascular endothelial cells via mitogen-activated protein kinase pathway

2021 ◽  
Vol 18 ◽  
Author(s):  
Li-yun Kong ◽  
Yan Li ◽  
Ding-yu Rao ◽  
Bing Wu ◽  
Cheng-peng Sang ◽  
...  
Keyword(s):  
Deep Sequencing ◽  
Glucose Deprivation ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Luciferase Assay ◽  
Microvascular Endothelial Cells ◽  
Oxygen Glucose Deprivation ◽  
Brain Microvascular Endothelial Cells ◽  
Protective Effects ◽  
Mitogen Activated Protein

Background: Previous studies have reported that mesenchymal stem cell (MSC)-derived exosomes can protect rat primary brain microvascular endothelial cells (BMECs) against oxygen–glucose deprivation and reoxygenation (OGD/R)-induced injury. Objective: To identify the key factors mediating the protective effects of MSC-derived exosomes. Methods: Rat primary BMECs were either pretreated or not pretreated with MSC-derived exosomes before exposure to OGD/R. Naïve cells were used as a control. After performing small RNA deep sequencing, quantitative reverse transcription polymerase chain reaction was performed to validate microRNA (miRNA) expression. The effects of rno-miR-666-3p on cell viability, apoptosis, and inflammation in OGD/R-exposed cells were assessed by performing the Cell Counting Kit 8 assay, flow cytometry, and enzyme-linked immunosorbent assay, respectively. Moreover, the role of rno-miR-666-3p in regulating gene expression in OGD/R-exposed cells was studied using mRNA deep sequencing. Lastly, to evaluate whether mitogen-activated protein kinase 1 (MAPK1) was the target of rno-miR-666-3p, western blotting and the dual-luciferase assay were performed. Results: MSC-derived exosomes altered the miRNA expression patterns in OGD/R-exposed BMECs. In particular, the expression levels of rno-miR-666-3p, rno-miR-92a-2-5p, and rno-miR-219a-2-3p decreased in OGD/R-exposed cells compared with those in the control; however, MSC-derived exosomes restored the expression levels of these miRNAs under OGD/R conditions. rno-miR-666-3p overexpression enhanced cell viability and alleviated the apoptosis of OGD/R-exposed cells. Moreover, rno-miR-666-3p suppressed OGD/R-induced inflammation. mRNA deep sequencing revealed that rno-miR-666-3p is closely associated with the MAPK signaling pathway. Western blotting and the dual-luciferase assay confirmed that MAPK1 is the target of rno-miR-666-3p. Conclusion: MSC-derived exosomes restore rno-miR-666-3p expression in OGD/R-exposed BMECs. Moreover, this specific miRNA exerts protective effects against OGD/R by suppressing the MAPK signaling pathway.

scholarly journals Uncovering the Pharmacological Mechanism of Stemazole in the Treatment of Neurodegenerative Diseases Based on a Network Pharmacology Approach

2020 ◽  
Vol 21 (2) ◽  
pp. 427 ◽  
Author(s):  
Jing Zhang ◽  
Huajun Li ◽  
Yubo Zhang ◽  
Chaoran Zhao ◽  
Yizi Zhu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Neurodegenerative Diseases ◽  
Molecular Mechanisms ◽  
Target Prediction ◽  
Mapk Signaling ◽  
Scientific Basis ◽  
Mitogen Activated Protein Kinase ◽  
Network Pharmacology ◽  
Protective Effects ◽  
Mitogen Activated Protein

Stemazole exerts potent pharmacological effects against neurodegenerative diseases and protective effects in stem cells. However, on the basis of the current understanding, the molecular mechanisms underlying the effects of stemazole in the treatment of Alzheimer’s disease and Parkinson’s disease have not been fully elucidated. In this study, a network pharmacology-based strategy integrating target prediction, network construction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and molecular docking was adopted to predict the targets of stemazole relevant to the treatment of neurodegenerative diseases and to further explore the involved pharmacological mechanisms. The majority of the predicted targets were highly involved in the mitogen-activated protein kinase (MAPK) signaling pathway. RAC-alpha serine/threonine-protein kinase (AKT1), caspase-3 (CASP3), caspase-8 (CASP8), mitogen-activated protein kinase 8 (MAPK8), and mitogen-activated protein kinase 14 (MAPK14) are the core targets regulated by stemazole and play a central role in its anti-apoptosis effects. This work provides a scientific basis for further elucidating the mechanism underlying the effects of stemazole in the treatment of neurodegenerative diseases.

Schisantherin-A Alleviates Lipopolysaccharide-Induced Inflammation and Apoptosis in WI-38 Cells

2021 ◽  
Vol 19 (4) ◽  
pp. 421-426
Author(s):  
Shan Liu ◽  
Banghao Lu
Keyword(s):  
Protein Kinase ◽  
Antioxidant Activities ◽  
Kidney Injury ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Extracellular Signal ◽  
Acute Pneumonia ◽  
Mitogen Activated Protein ◽  
Anti Inflammatory ◽  
Schisantherin A

Schisantherin A, a dibenzocyclooctadiene lignan, isolated from the fruit of Schisandra sphenanthera has been widely used to exert anti-inflammatory or antioxidant activities in sepsis associated acute kidney injury and lipopolysaccharide associated acute respiratory distress syndrome. However, the protective effects of Schisantherin A against acute pneumonia in lipopolysaccharide-induced WI-38 remain to be explored. To this end, WI-38 cells were treated with lipopolysaccharide to establish an acute pneumonia model and evaluate the effect of Schisantherin A. The data show an increase in apoptosis and decrease in cell viability by lipopolysaccharide treatment that was reversed by Schisantherin A. Also, Schisantherin A dose dependently attenuated lipopolysaccharide-induced increase in proinflammatory cytokines. Lastly, expression of p65, p38 proteins, extracellular-signal-regulated kinase, and Jun N-terminal protein kinase phosphorylation were upregulated by lipopolysaccharide and decreased by Schisantherin A. In conclusion, Schisantherin A demonstrates anti-inflammatory and antiapoptotic roles in lipopolysaccharide induced WI-38 cells through inactivation of nuclear factor-kappa B/mitogen activated protein kinase pathway.

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