Activation of protein kinase B/Akt signaling pathway contributes to mechanical hypersensitivity induced by capsaicin

Pain ◽  
2006 ◽  
Vol 120 (1-2) ◽  
pp. 86-96 ◽  
Author(s):  
Rui-Qing Sun ◽  
Yi-Jun Tu ◽  
Jing-Yin Yan ◽  
William D. Willis
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Protein Kinase B ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Mechanical Hypersensitivity

scholarly journals Downregulation of cAMP-Dependent Protein Kinase Inhibitor-b Promotes Preeclampsia by Decreasing Phosphorylated Akt

2020 ◽  
Vol 28 (1) ◽  
pp. 178-185
Author(s):  
Chunfeng Liu ◽  
Hao Wang ◽  
Mo Yang ◽  
Yiheng Liang ◽  
Li Jiang ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Matrix Metalloproteinase ◽  
Signaling Pathway ◽  
Kinase Inhibitor ◽  
Akt Signaling ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Dependent Protein Kinase ◽  
Phosphorylated Akt ◽  
Dependent Protein

AbstractPreeclampsia is a multi-system disease that is unique to human pregnancy. Impaired extravillous trophoblast migration and invasion accompanied by poor spiral vascular remodeling is thought to be the initial reason. This study investigated cAMP-dependent protein kinase inhibitor-b(PKIB) expression in placentas and its involvement in the pathogenesis of PE. We used immunohistochemistry and western blotting to calculate PKIB levels in the placentas. Then we knocked down PKIB by siRNA and used real-time cell analysis to assess the invasion and migration ability of trophoblasts. Tube formation assay and spheroid sprouting assay were utilized to identify the ability to form vessels of trophoblasts. At last, western blotting was used to demonstrate the level of phosphorylated Akt, as well as downstream-related genes of Akt signaling pathway in trophoblasts. We first found that PKIB expression level was lower in the PE placentas than in the normal placentas. In addition, we found that downregulation of PKIB can inhibit the migration, invasion, and the ability to form vessels of HTR8/SVneo cells. Downregulation of PKIB leaded to a decrease in phosphorylated Akt, as well as downstream proteins such as matrix metalloproteinase 2, matrix metalloproteinase 9, and glycogen synthase kinase 3β, which are related to migration and invasion. Our study revealed that the downregulation of PKIB expression resulted in decreased migration, invasion, and vessel formation ability by regulating Akt signaling pathway in placental trophoblasts in PE.

scholarly journals Asiatic acid attenuates hypertrophic and fibrotic differentiation of articular chondrocytes via AMPK/PI3K/AKT signaling pathway

2020 ◽  
Author(s):  
Na Liu ◽  
Dejie Fu ◽  
Junjun Yang ◽  
Pingju Liu ◽  
Xiongbo Song ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Type I Collagen ◽  
Articular Chondrocytes ◽  
Akt Signaling ◽  
Type I ◽  
Asiatic Acid ◽  
Akt Signaling Pathway ◽  
Chondrocyte Hypertrophy ◽  
Chondrogenic Phenotype

Abstract Background: Osteoarthritis (OA), the most common joint disorder, is characterized by a progressive degradation of articular cartilage. Increasing evidence suggests that OA is closely associated with cartilage pathologies including chondrocyte hypertrophy and fibrosis. Methods: In this study, we showed that asiatic acid (AA) treatment reduced chondrocyte hypertrophy and fibrosis. First, the cytotoxicity of AA (0, 5, 10, and 20 μM) to chondrocytes was evaluated, and 5 μM was selected for subsequent experiments. Then, we detected the gene and protein level of chondrocyte hypertrophic markers including type X collagen (COL-X), matrix metalloproteinase - 13 (MMP-13), alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), and chondrocyte fibrosis markers including type I collagen (COL-Ι) and alpha-smooth muscle actin (α-SMA), and chondrogenic markers including SRY-related HMG box 9 (SOX9), type II collagen (COL-II) and aggrecan (ACAN). Further, we tested the mechanism of AA on inhibiting chondrocyte hypertrophy and fibrosis. Finally, we verified the results in an anterior cruciate ligament transection (ACLT) rat OA model.Results: We found that AA treatment inhibited the hypertrophic and fibrotic phenotype of chondrocytes, without affecting the chondrogenic phenotype. Moreover, we found that AA treatment activated AMP-activated protein kinase (AMPK) and inhibited phosphoinositide-3 kinase/protein kinase B (PI3K/AKT) signaling pathway in vitro. The results in an ACLT-rat OA model also indicated that AA significantly attenuated chondrocyte hypertrophy and fibrosis. Conclusion: AA treatment could reduce hypertrophic and fibrotic differentiation, and maintain the chondrogenic phenotype of articular chondrocytes by targeting the AMPK/PI3K/AKT signaling pathway. Our study suggested that AA might be a prospective drug component that targets hypertrophic and fibrotic chondrocytes for OA treatment.

scholarly journals Modulatory effect of curcumin on ketamine-induced toxicity in rat thymocytes: Involvement of reactive oxygen species (ROS) and the phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) pathway

2018 ◽  
Vol 18 (4) ◽  
pp. 320-327 ◽  
Author(s):  
Svetlana Pavlovic ◽  
Zorica Jovic ◽  
Radmila Karan ◽  
Dane Krtinic ◽  
Gorana Rankovic ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Flow Cytometry ◽  
Protein Kinase ◽  
Caspase 3 ◽  
Protein Kinase B ◽  
Akt Signaling ◽  
Ros Production ◽  
Oxygen Species ◽  
Akt Signaling Pathway ◽  
Phosphoinositide 3 Kinase

Ketamine is a widely used anesthetic in pediatric clinical practice. Previous studies have demonstrated that ketamine induces neurotoxicity and has a modulatory effect on the cells of the immune system. Here, we evaluated the potential protective effect and underlying mechanisms of natural phenolic compound curcumin against ketamine-induced toxicity in rat thymocytes. Rat thymocytes were exposed to 100 µM ketamine alone or combined with increasing concentrations of curcumin (0.3, 1, and 3 μM) for 24 hours. Cell viability was analyzed with CCK-8 assay kit. Apoptosis was analyzed using flow cytometry and propidium iodide as well as Z-VAD-FMK and Z-LEHD-FMK inhibitors. Reactive oxygen species (ROS) production and mitochondrial membrane potential [MMP] were measured by flow cytometry. Colorimetric assay with DEVD-pNA substrate was used for assessing caspase-3 activity. Involvement of phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway was tested with Wortmannin inhibitor. Ketamine induced toxicity in cells, increased the number of hypodiploid cells, caspase-3 activity and ROS production, and inhibited the MMP. Co-incubation of higher concentrations of curcumin (1 and 3 μM) with ketamine markedly decreased cytotoxicity, apoptosis rate, caspase-3 activity, and ROS production in rat thymocytes, and increased the MMP. Application of Z-VAD-FMK (a pan caspase inhibitor) or Z-LEHD-FMK (caspase-9 inhibitor) with ketamine effectively attenuated the ketamine-induced apoptosis in rat thymocytes. Administration of Wortmannin (a PI3K inhibitor) with curcumin and ketamine significantly decreased the protective effect of curcumin on rat thymocytes. Our results indicate that ketamine-induced toxicity in rat thymocytes mainly occurs through the mitochondria-mediated apoptotic pathway and that the PI3K/Akt signaling pathway is involved in the anti-apoptotic effect of curcumin.

scholarly journals LncRNA MIR205HG accelerates cell proliferation, migration and invasion in hepatoblastoma through the activation of MAPK signaling pathway and PI3K/AKT signaling pathway

2022 ◽  
Vol 17 (1) ◽  
Author(s):  
Wei Zhang ◽  
Feng Liang ◽  
Qingfeng Li ◽  
Hong Sun ◽  
Fei Li ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Akt Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Migration And Invasion ◽  
Akt Signaling Pathway ◽  
Liver Malignancy ◽  
Mitogen Activated Protein

Abstract Background Hepatoblastoma (HB) is identified to be the most common liver malignancy which occurs in children. Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes and diseases, including HB. LncRNA MIR205 host gene (MIR205HG) has been investigated in multiple cancers, however, its role in HB remains to be elucidated. Methods MIR205HG expression was analyzed by RT-qPCR. EdU, colony formation and transwell assays were implemented to measure the biological function of MIR205HG on the progression of HB. Mechanism assays were carried out to probe into the underlying mechanism of MIR205HG in HB cells. Results MIR205HG was significantly overexpressed in HB. Moreover, MIR205HG inhibition suppressed the proliferative, migratory and invasive capacities of HB cells. Furthermore, MIR205HG competitively bound to microRNA-514a-5p (miR-514a-5p) and targeted mitogen-activated protein kinase 9 (MAPK9) to stimulate mitogen activated protein kinase (MAPK) signaling pathway. Besides, MIR205HG also served as a sponge for microRNA-205-5p (miR-205-5p) to activate the PI3K/AKT signaling pathway. Conclusion MIR205HG drives the progression of HB which might provide an efficient marker and new therapeutic target for HB.

scholarly journals Protein Kinase C-  Mediates Neuronal Apoptosis in the Retinas of Diabetic Rats via the Akt Signaling Pathway

Diabetes ◽  
2008 ◽  
Vol 57 (8) ◽  
pp. 2181-2190 ◽  
Author(s):  
Y.-H. Kim ◽  
Y.-S. Kim ◽  
C.-H. Park ◽  
I.-Y. Chung ◽  
J.-M. Yoo ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Neuronal Apoptosis ◽  
Akt Signaling ◽  
Diabetic Rats ◽  
Akt Signaling Pathway ◽  
Kinase C

scholarly journals sMEK1 promotes crosstalk between IRE1 and Akt signaling pathway: Evidence for a novel IRE1/sMEK1/Akt complex

2021 ◽  
Author(s):  
ozaira qadri ◽  
Samirul Bashir ◽  
Mariam Banday ◽  
Nazia Hilal ◽  
Khalid M Fazili
Keyword(s):  
Protein Kinase ◽  
Er Stress ◽  
Signaling Pathway ◽  
Molecular Mechanism ◽  
Ternary Complex ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Unfolded Protein ◽  
Central Molecule ◽  
Protein Response

ER is facilitated with a dynamic cellular pathway namely Unfolded Protein Response (UPR): an adaptive signalling mechanism that maintains proteostasis in response to ER stress. IRE1 is one of the three transmembrane sensors of UPR with dual protein kinase and ribonuclease activities. IRE1 acts as a central molecule of UPR, which associates with a number of proteins that either regulate its activity or connect it to other pathways. Here, we report sMEK1 and Akt as novel interacting partners of IRE1 which associate to orchestrate the IRE1 and Akt signalling networks. Our study revealed that ER stress negatively regulates Akt through IRE1 protein. We found that IRE1/sMEK1/Akt form a ternary complex, which results in the dephosphorylation of Akt by protein phosphotase sMEK1 in presence of activated IRE1. Together, this study highlights the UPR/Akt link by delineating the molecular mechanism along with giving insights into the overall impact of this interaction.

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