scholarly journals Treadmill exercise activates PI3K/Akt signaling pathway leading to GSK-3β inhibition in the social isolated rat pups

2018 ◽  
Vol 14 (1) ◽  
pp. 4-9 ◽  
Author(s):  
Lin Ru Wang ◽  
Seung-Soo Baek
Keyword(s):  
Signaling Pathway ◽  
Treadmill Exercise ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Rat Pups ◽  
The Social ◽  
Gsk 3Β ◽  
Isolated Rat

scholarly journals Phosphorylated GSK‑3β protects stress‑induced apoptosis of myoblasts via the PI3K/Akt signaling pathway

2020 ◽  
Vol 22 (1) ◽  
pp. 317-327
Author(s):  
Meixi Liu ◽  
Xia Huang ◽  
Yihong Tian ◽  
Xiao Yan ◽  
Fang Wang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gsk 3Β ◽  
Induced Apoptosis

PTEN influences insulin and lipid metabolism in bovine hepatocytes in vitro

2019 ◽  
Vol 86 (1) ◽  
pp. 73-76 ◽  
Author(s):  
Qinghua Deng ◽  
Dehui Ma ◽  
Guoquan Sun ◽  
Xue Yuan ◽  
Zhe Wang ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Fatty Liver ◽  
Dairy Cows ◽  
Signaling Pathway ◽  
Fatty Acid Synthase ◽  
Akt Signaling ◽  
Negative Regulator ◽  
Akt Signaling Pathway ◽  
Gsk 3Β

AbstractDairy cows with fatty liver or ketosis display decreased insulin sensitivity and defects in the insulin receptor substrate (IRS)/PI3K/AKT signaling pathway. Phosphatase and tensin homolog (PTEN) is a well-known tumor suppressor and also a negative regulator of insulin signaling and peripheral insulin sensitivity. We investigated the hypothesis that PTEN may affect the insulin pathway-mediated hepatic glucose and lipid metabolism in dairy cows. Adenovirus vectors that over-express and silence PTEN were constructed, and then transfected into hepatocytes isolated from calves to investigate the effect of PTEN on PI3K/AKT signaling pathway. PTEN silencing increased the phosphorylation of AKT and the expression of PI3K but decreased the phosphorylation of IRS1, which increased the phosphorylation levels of glycogen synthase kinase-3β (GSK-3β) and expression of sterol regulatory element-binding protein-1c (SREBP-1c). Increased GSK-3β phosphorylation further up-regulated expression of the key enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6-Pase) involved in gluconeogenesis. Furthermore, the expression of SREBP-1c target gene fatty acid synthase (FAS) also increased significantly. We further showed that PTEN over-expression could reverse the above results. PTEN negatively regulates the enzymes involved in hepatic gluconeogenesis and lipid synthesis, which suggests that PTEN may be a therapeutic target for ketosis and fatty liver in dairy cows.

scholarly journals Combination of Paeoniflorin and Calycosin-7-glucoside Promotes Ischemic Stroke Recovery via the PI3K/AKT Signaling Pathway

2020 ◽  
Author(s):  
shengxin Wang ◽  
Xiangli Yan ◽  
Yingying He ◽  
Haozhen Zheng ◽  
PengCheng Wang ◽  
...  
Keyword(s):  
Reperfusion Injury ◽  
Signaling Pathway ◽  
Therapeutic Effect ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Glucose Deprivation ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gsk 3Β

Abstract Background Paeoniflorin (PF) and calycosin-7-glucoside (CG) play a role in protecting against brain damage following cerebral ischemia. However, the mechanism of action of PF in combination with CG (PF + CG) against ischemia/reperfusion injury remains unclear. Methods The aim of this study was to investigate the protective role of PF + CG on ischemia/reperfusion injury in vivo and in vitro, as well as its potential mechanism of action indicating that PF + CG attenuates middle cerebral artery occlusion (MCAO) /oxygen-glucose deprivation reperfusion (OGD/R) injury via the PI3K/AKT pathway. MCAO rat model was prepared by modified suture method, and behavioral scoring, cerebral infarction area, brain tissue water content measurement, using PI3K, p-PI3K, AKT, p-AKT, Bcl-2, Bax, GSK-3β protein expression as indicators, observe the effect of PI3K / AKT signaling pathway inhibitor LY294002 on the anti-ischemia-reperfusion effect of PF + CG. Oxygen deprivation method was used to prepare the OGD/R model, CCK-8 was used to determine the survival rate of HT22 cells, the contents of SOR, ROS, MDA, and LHD were determined, and apoptosis was detected by flow cytometry and mitochondrial membrane potential, using PI3K, p-PI3K, AKT, p-AKT, Bcl-2, Bax, GSK-3β protein expression as indicators, observe the effect of PI3K/AKT signaling pathway inhibitor LY294002 on the anti- oxidative and glucose deprivation effect of PF + CG. Results The animal studies showed that PF + CG significantly decreased neurobehavioral deficits, cerebral infarct volume, and brain edema; ameliorated histopathological damage in model rats; increased levels of PI3K, AKT, p-PI3K, p-AKT, and Bcl-2; and reduced BAX and GSK-3β expression. After treatment with PF + CG, the morphology and number of cells in brain tissue were restored to normal, demonstrating a therapeutic effect in cerebral ischemia-reperfusion injury. Results of further studies revealed that, in vitro, PF + CG has a therapeutic effect to enhance cell vitality; elevate levels of superoxide dismutase (SOD); reduce levels of reactive oxygen species (ROS), lactate dehydrogenase (LDH), and malondialdehyde (MDA); decrease apoptosis rate; increase levels of PI3K, AKT, p-PI3K, p-AKT, and Bcl-2; and reduce BAX and GSK-3β expression. Conclusion These results demonstrate that PF + CG has a positive therapeutic effect on ischemia/reperfusion and OGD/R injury, and the mechanism is attributed to activation of the PI3K/AKT signaling pathway.

scholarly journals Extremely Low-Frequency Electromagnetic Fields Increase the Expression of Anagen-Related Molecules in Human Dermal Papilla Cells via GSK-3β/ERK/Akt Signaling Pathway

2020 ◽  
Vol 21 (3) ◽  
pp. 784
Author(s):  
Ga-Eun Ki ◽  
Yu-Mi Kim ◽  
Han-Moi Lim ◽  
Eun-Cheol Lee ◽  
Yun-Kyong Choi ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Electromagnetic Fields ◽  
Low Frequency ◽  
Dermal Papilla ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Androgenic Alopecia ◽  
Dermal Papilla Cells ◽  
Extremely Low Frequency ◽  
Gsk 3Β

Despite advances in medical treatments, the proportion of the population suffering from alopecia is increasing, thereby creating a need for new treatments to control hair loss and prevent balding. Human hair follicle dermal papilla cells (hDPCs), a type of specialized fibroblast in the hair bulb, play an essential role in controlling hair growth and in conditions like androgenic alopecia. This study aimed to evaluate the intensity-dependent effect of extremely low-frequency electromagnetic fields (ELF-EMFs) on the expression of anagen-related molecules in hDPCs in vitro. We examined the effect of ELF-EMF on hDPCs to determine whether activation of the GSK-3β/ERK/Akt signaling pathway improved hDPC activation and proliferation; hDPCs were exposed to ELF-EMFs at a frequency of 70 Hz and at intensities ranging from 5 to 100 G, over four days. Various PEMF intensities significantly increased the expression of anagen-related molecules, including collagen IV, laminin, ALP, and versican. In particular, an intensity of 10 G is most potent for promoting the proliferation of hDPC and expression of anagen-related molecules. Moreover, 10 G ELF-EMF significantly increased β-catenin and Wnt3α expression and GSK-3β/ERK/Akt phosphorylation. Our results confirmed that ELF-EMFs enhance hDPC activation and proliferation via the GSK-3β/ERK/Akt signaling pathway, suggesting a potential treatment strategy for alopecia.

scholarly journals PI3K/AKT Signal Pathway: A Target of Natural Products in the Prevention and Treatment of Alzheimer’s Disease and Parkinson’s Disease

2021 ◽  
Vol 12 ◽  
Author(s):  
Hui-Zhi Long ◽  
Yan Cheng ◽  
Zi-Wei Zhou ◽  
Hong-Yu Luo ◽  
Dan-Dan Wen ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Parkinson’S Disease ◽  
Alzheimer's Disease ◽  
Parkinson's Disease ◽  
Natural Products ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Gsk 3Β

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two typical neurodegenerative diseases that increased with aging. With the emergence of aging population, the health problem and economic burden caused by the two diseases also increase. Phosphatidylinositol 3-kinases/protein kinase B (PI3K/AKT) signaling pathway regulates signal transduction and biological processes such as cell proliferation, apoptosis and metabolism. According to reports, it regulates neurotoxicity and mediates the survival of neurons through different substrates such as forkhead box protein Os (FoxOs), glycogen synthase kinase-3β (GSK-3β), and caspase-9. Accumulating evidences indicate that some natural products can play a neuroprotective role by activating PI3K/AKT pathway, providing an effective resource for the discovery of potential therapeutic drugs. This article reviews the relationship between AKT signaling pathway and AD and PD, and discusses the potential natural products based on the PI3K/AKT signaling pathway to treat two diseases in recent years, hoping to provide guidance and reference for this field. Further development of Chinese herbal medicine is needed to treat these two diseases.

20(S)-Protopanaxadiol Triggers Mitochondrial-Mediated Apoptosis in Human Lung Adenocarcinoma A549 Cells via Inhibiting the PI3K/Akt Signaling Pathway

2013 ◽  
Vol 41 (05) ◽  
pp. 1137-1152 ◽  
Author(s):  
Yun-Long Zhang ◽  
Rui Zhang ◽  
Hua-Li Xu ◽  
Xiao-Feng Yu ◽  
Shao-Chun Qu ◽  
...  
Keyword(s):  
Lung Adenocarcinoma ◽  
Signaling Pathway ◽  
Human Lung ◽  
A549 Cells ◽  
Akt Signaling ◽  
Akt Signaling Pathway ◽  
Human Lung Adenocarcinoma ◽  
Lung Adenocarcinoma A549 ◽  
Gsk 3Β ◽  
Induced Apoptosis

20(S)-Protopanaxadiol (PPD), an aglycone saponin ginsenoside isolated from Panax quinquefolium L, has been shown to inhibit the growth and proliferation in several cancer lines. However, the underlying molecular mechanisms remain poorly understood. In this study, we investigated the apoptosis-induced effects and the mechanism of 20(S)-PPD on human lung adenocarcinoma A549 cells. 20(S)-PPD showed a potent antiproliferative activity against A549 cells by triggering apoptosis. 20(S)-PPD-induced apoptosis was characterized by a dose-dependent loss of the mitochondrial membrane, release of cytochrome c, second mitochondria-derived activator of caspase (Smac) and apoptosis-inducing factor (AIF), activation of caspase-9/-3, and cleavage of poly (ADP-ribose) polymerase (PARP). Caspase-dependence was indicated by the ability of the pan-caspase inhibitor z-VAD-fmk to attenuate 20(S)-PPD-induced apoptosis. After treatment with 20(S)-PPD, the proportion of A549 cells at the G0/G1 phase increased, while cells at the S and G2/M phases decreased. Furthermore, 20(S)-PPD also triggered down-regulation of phosphorylated Akt (Ser473/Thr308) and glycogen synthase kinase 3β (GSK 3β). Knockdown of GSK 3β with siRNA promoted the apoptotic effects of 20(S)-PPD. These results revealed an unexpected mechanism of action for this unique ginsenoside: triggering a mitochondrial-mediated, caspase-dependent apoptosis via down-regulation of the PI3K/Akt signaling pathway in A549 cells. Our findings encourage further studies of 20(S)-PPD as a promising chemopreventive agent against lung cancer.

scholarly journals The Phosphoinositide-3-Kinase–Akt Signaling Pathway Is Important for Staphylococcus aureus Internalization by Endothelial Cells

2011 ◽  
Vol 79 (11) ◽  
pp. 4569-4577 ◽  
Author(s):  
Javier Oviedo-Boyso ◽  
Ricarda Cortés-Vieyra ◽  
Alejandro Huante-Mendoza ◽  
Hong B. Yu ◽  
Juan J. Valdez-Alarcón ◽  
...  
Keyword(s):  
Staphylococcus Aureus ◽  
Endothelial Cells ◽  
Signaling Pathway ◽  
Glycogen Synthase ◽  
Akt Signaling ◽  
Dominant Negative ◽  
Akt Signaling Pathway ◽  
Content Type ◽  
Gsk 3Β ◽  
Phosphoinositide 3 Kinase

ABSTRACTInternalization ofStaphylococcus aureusin bovine endothelial cells (BEC) is increased by tumor necrosis factor alpha stimulation and NF-κB activation. Because the phosphoinositide-3-kinase (PI3K)–Akt signaling pathway also modulates NF-κB activity, we considered whether the internalization ofS. aureusby BEC is associated with the activity of PI3K and Akt. We found a time- and multiplicity of infection-dependent phosphorylation of Akt on Ser473 in BEC infected withS. aureus. This phosphorylation was inhibited by LY294002 (LY), indicating the participation of PI3K. Inhibition of either PI3K with LY or wortmannin, or Akt with SH-5, strongly reduced the internalization ofS. aureus. Transfection of BEC with a dominant-negative form of the Akt gene significantly decreasedS. aureusinternalization, whereas transfection with the constitutively active mutant increased the number of internalized bacterium. Inhibition of PDK1 activity with OSU-03012 did not affect the level ofS. aureusinternalization, demonstrating that phosphorylation of Akt on Thr308 is not important for this process. Compared to the untreated control, the adherence ofS. aureusto the surface of BEC was unaltered when cells were transfected or incubated with the pharmacological inhibitors. Furthermore, Akt activation by internalizedS. aureustriggered a time-dependent phosphorylation of glycogen synthase kinase-3α (GSK-3α) on Ser21 and GSK-3β on Ser9 that was partially inhibited with SH-5. Finally, treatment of BEC with LY prior toS. aureusinfection inhibited the NF-κB p65 subunit phosphorylation on Ser536, indicating the involvement of PI3K. These results suggest that PI3K-Akt activity is important for the internalization ofS. aureusand phosphorylation of GSK-3α, GSK-3β, and NF-κB.

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