scholarly journals Cyclophosphamide Inhibits PI3K/AKT/mTOR Signaling Pathway in Mice Kidneys

Proceedings ◽  
2018 ◽  
Vol 2 (25) ◽  
pp. 1587 ◽  
Author(s):  
Gulsah Albayrak ◽  
Pinar Kilicarslan Sonmez ◽  
Damla Akogullari ◽  
Elgin Turkoz Uluer
Keyword(s):  
Cell Cycle ◽  
Protein Synthesis ◽  
Signaling Pathway ◽  
Cell Cycle Regulation ◽  
Kidney Tissue ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Cellular Functions ◽  
Cycle Regulation ◽  
Experimental Group

Cyclophosphamide (CTX), also known as cytophosphane among other, is a medication used as chemotherapy and to suppress the immune system. The PI3K/AKT/mTOR pathway is involved in the regulation of diverse cellular functions, including cell growth, protein synthesis, cell cycle regulation, glucose metabolism, and motility. In our study eight weeks old C57BL/6 female mice were divided into 3 groups as control (C), sham (S) and experimental group. The experimental group has been established with CTX treatment. No treatment was applied to the C group. The S group were given an equal amount of saline. CTX was administered intraperitoneally one every 2 days for 3 weeks; the first dose was 70 mg/kg, the ongoing doses were 30 mg/kg. At the end of 3 weeks mice were sacrificed and kidneys were taken for investigation. In order to show the effect of cyclophosphamide in kidney tissue, the tissues were stained via indirect immunohistochemistry with PI3K, AKT and mTOR primary antibodies. In our study, PI3K, AKT and mTOR expression levels were found to be significantly decreased in CTX-mediated mechanisms indicating that the mechanisms of CTX might involve in the inhibition of PI3K/AKT/mTOR signaling pathway.

scholarly journals The Rb-CDK4/6 Signaling Pathway Is Critical in Neural Precursor Cell Cycle Regulation

2000 ◽  
Vol 275 (43) ◽  
pp. 33593-33600 ◽  
Author(s):  
Kerry L. Ferguson ◽  
Steven M. Callaghan ◽  
Michael J. O'Hare ◽  
David S. Park ◽  
Ruth S. Slack
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Cell Cycle Regulation ◽  
Precursor Cell ◽  
Neural Precursor ◽  
Neural Precursor Cell ◽  
Cycle Regulation

l-Arginine stimulates the mTOR signaling pathway and protein synthesis in porcine trophectoderm cells

2012 ◽  
Vol 23 (9) ◽  
pp. 1178-1183 ◽  
Author(s):  
Xiangfeng Kong ◽  
Bie Tan ◽  
Yulong Yin ◽  
Haijun Gao ◽  
Xilong Li ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Trophectoderm Cells

Leucine-stimulated mTOR signaling is partly attenuated in skeletal muscle of chronically uremic rats

2011 ◽  
Vol 301 (5) ◽  
pp. E873-E881 ◽  
Author(s):  
Yu Chen ◽  
Sumita Sood ◽  
Kevin McIntire ◽  
Richard Roth ◽  
Ralph Rabkin
Keyword(s):  
Skeletal Muscle ◽  
Protein Synthesis ◽  
Signaling Pathway ◽  
Muscle Wasting ◽  
Muscle Protein ◽  
Muscle Protein Synthesis ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Exercise Induced ◽  
Rps6 Phosphorylation

The branched-chain amino acid leucine stimulates muscle protein synthesis in part by directly activating the mTOR signaling pathway. Furthermore, leucine, if given in conjunction with resistance exercise, enhances the exercise-induced mTOR signaling and protein synthesis. Here we tested whether leucine can activate the mTOR anabolic signaling pathway in uremia and whether it can enhance work overload (WO)-induced signaling through this pathway. Chronic kidney disease (CKD) and control rats were studied after 7 days of surgically induced unilateral plantaris muscle WO and a single leucine or saline load. In the basal state, 4E-BP1 phosphorylation was modestly depressed in non-WO muscle of CKD rats, whereas rpS6 phosphorylation was nearly completely suppressed. After oral leucine mTOR, S6K1 and rpS6 phosphorylation increased similarly in both groups, whereas the phospho-4E-BP1 response was modestly attenuated in CKD. WO alone activated the mTOR signaling pathway in control and CKD rats. In WO CKD, muscle leucine augmented mTOR and 4E-BP1 phosphorylation, but its effect on S6K1 phosphorylation was attenuated. Taken together, this study has established that the chronic uremic state impairs basal signaling through the mTOR anabolic pathway, an abnormality that may contribute to muscle wasting. However, despite this abnormality, leucine can stimulate this signaling pathway in CKD, although its effectiveness is partially attenuated, including in skeletal muscle undergoing sustained WO. Thus, although there is some resistance to leucine in CKD, the data suggest a potential role for leucine-rich supplements in the management of uremic muscle wasting.

scholarly journals EPHA2 Promotes the Invasion and Migration of Human Tongue Squamous Cell Carcinoma Cal-27 Cells by Enhancing AKT/mTOR Signaling Pathway

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Fengqin Wang ◽  
Hanzhong Zhang ◽  
Zhigang Cheng
Keyword(s):  
Cell Cycle ◽  
Signaling Pathway ◽  
Mtor Inhibitor ◽  
Mtor Signaling ◽  
Biological Behavior ◽  
Migration And Invasion ◽  
Mtor Signaling Pathway ◽  
Akt Inhibitor ◽  
Invasion And Migration ◽  
And Migration

EPHA2 is a member of the ephrin receptor tyrosine kinase family and is closely related to the malignant tumor progression. The effect of EPHA2 on OSCC is not clear. This study explored the role of EPHA2 and AKT/mTOR signaling pathways in Cal-27 cell invasion and migration. The expression of EPHA2 and EPHA4 in human OSCC and normal oral tissue was detected by immunohistochemistry. EPHA2-overexpressing and EPHA2-knockdown Cal-27 cells were established, and the cells were treated with an AKT inhibitor (MK2206) and mTOR inhibitor (RAD001). The expression of EPHA2 was detected by qRT-PCR, cell proliferation was evaluated by MTT assay, cell migration and invasion were examined by scratch and Transwell assay, and cell morphology and apoptosis were assessed by Hoechst 33258 staining. Western blot was performed to detect the expression of proteins related to AKT/mTOR signaling, cell cycle, and pseudopod invasion. EPHA2 and EPHA4 were highly expressed in clinical human OSCC. Overexpression of EPHA2 promoted the proliferation, migration, and invasion of Cal-27 cells, inhibited cell cycle blockage and apoptosis, and enhanced the activity of the AKT/mTOR signaling pathway. MK2206 (AKT inhibitor) and RAD001 (mTOR inhibitor) reversed the effect of EPHA2 overexpression on the biological behavior of Cal-27 cells. EPHA2 promotes the invasion and migration of Cal-27 human OSCC cells by enhancing the AKT/mTOR signaling pathway.

scholarly journals Cell Cycle Arrest of Extract from Artemisia annua Linné. Via Akt-mTOR Signaling Pathway in HCT116 Colon Cancer Cells

KSBB Journal ◽  
2015 ◽  
Vol 30 (5) ◽  
pp. 223-229 ◽  
Author(s):  
Bo Min Kim ◽  
Guen Tae Kim ◽  
Eun Gyeong Lim ◽  
Eun Ji Kim ◽  
Sang Yong Kim ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Colon Cancer ◽  
Cell Cycle Arrest ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Artemisia Annua ◽  
Mtor Signaling ◽  
Colon Cancer Cells ◽  
Mtor Signaling Pathway ◽  
Cycle Arrest

scholarly journals Early leucine programming  on  protein utilization and mTOR signaling by DNA methylation in zebrafish (Danio rerio)

2020 ◽  
Author(s):  
Qiang-Sheng Zhu ◽  
Jie Wang ◽  
shan he ◽  
Xu-Fang Liang ◽  
Shuang Xie ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Protein Synthesis ◽  
Amino Acid ◽  
Signaling Pathway ◽  
Danio Rerio ◽  
Mtor Signaling ◽  
Translation Initiation Factor ◽  
Mtor Signaling Pathway ◽  
Nutritional Programming ◽  
Expression Of Genes

Abstract Background Early nutritional programming affects a series of metabolism, growth and development in mammals. Fish also exhibit the developmental plasticity by early nutritional programming. However, little is known about the effect of early amino acid programming on growth and metabolism. Methods In the present study, zebrafish (Danio rerio) was used as the experimental animal to study whether early leucine stimulation can programmatically affect the mechanistic target of rapamycin (mTOR) signaling pathway, growth and metabolism in the later life, and to undercover the mechanism of epigenetic regulation. Zebrafish larvas at 3 days post hatching (dph) were raised with 1.0% leucine from 3 to 13 dph during the critical developmental stage, then back to normal water for 70 days (83 dph). Results The growth performance and crude protein content of zebrafish in the early leucine programming group were increased, and consistent with the activation of the mTOR signaling pathway and the high expression of genes involved in the metabolism of amino acid and glycolipid. Furthermore, we compared the DNA methylation profiles between the control and leucine-stimulated zebrafish, and found that the methylation levels of CG-differentially methylated regions (DMGs) and CHH-DMGs of genes involved in mTOR signaling pathway were different between the two groups. With quantitative PCR analysis, the decreased methylation levels of CG type of Growth factor receptor-bound protein 10 (Grb10), eukaryotic translation initiation factor 4E (eIF4E) and mTOR genes of mTOR signaling pathway in the leucine programming group, might contribute to the enhanced gene expression. Conclusions The early leucine programming could improve the protein synthesis and growth, which might be attributed to the methylation of genes in mTOR pathway and the expression of genes involved in protein synthesis and glycolipid metabolism in zebrafish. These results could be beneficial for better understanding of the epigenetic regulatory mechanism of early nutritional programming.

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