Effects of aerobic exercise training on the protein kinase B (PKB)/mammalian target of rapamycin (mTOR) signaling pathway in aged skeletal muscle

Gambogic acid (GA) is a natural compound with a polyprenylated xanthone structure that has antiinflammatory, antioxidant, and neuroprotective properties and acts as a chemopreventive agent. GA exhibits anti-tumor, antimicrobial, and anti-proliferative effects on cancer cells. In the current study, the effect of GA on phosphoinositide kinase-3 (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway was examined in human U251 glioma cells. Cell viability and apoptosis were evaluated by MTT and Annexin V/PI Double Staining. The expressions of P38, AKT, and mTOR were evaluated by western blot and qRT-PCR, respectively. MagBeads Total RNA Extraction Kit was used to isolate cell tissue RNA. GA decreased the phosphorylation of P38, AKT, and mTOR. Inhibitors of PI3K (LY294002) enhanced the phosphorylation of P38, AKT, and mTOR. GA reduced the phosphorylation of ribosomal protein precursors (Pre) and upstream binding factor (UBF), and insulin-like growth factor I (IGF-1) further enhanced the cell proliferation and expression of Pre and UBF. These results suggested that downregulation of PI3K/AKT/mTOR signaling pathway may be an important mediator in GA-affected ribosomal occurrence in glioma cells.

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Octreotide activates autophagy to alleviate lipopolysaccharide-induced human pulmonary epithelial cell injury by inhibiting the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway

Bioengineered ◽

10.1080/21655979.2021.2012908 ◽

2021 ◽

Author(s):

Sumian Zhang ◽

Cijun Tang ◽

Xuebin Wang

Keyword(s):

Protein Kinase ◽

Epithelial Cell ◽

Signaling Pathway ◽

Cell Injury ◽

Protein Kinase B ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

Mtor Signaling Pathway ◽

Pulmonary Epithelial Cell

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Effect of Supplemental Dietary Zinc on the Mammalian Target of Rapamycin (mTOR) Signaling Pathway in Skeletal Muscle and Liver from Post-absorptive Mice

Biological Trace Element Research ◽

10.1007/s12011-007-0018-8 ◽

2007 ◽

Vol 118 (1) ◽

pp. 65-76 ◽

Cited By ~ 22

Author(s):

James P. McClung ◽

Tyson N. Tarr ◽

Brian R. Barnes ◽

Angus G. Scrimgeour ◽

Andrew J. Young

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

Mtor Signaling Pathway ◽

Dietary Zinc

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Changes in muscle mass with mechanical load: possible cellular mechanismsThis paper is one of a selection of papers published in this Special Issue, entitled 14th International Biochemistry of Exercise Conference – Muscles as Molecular and Metabolic Machines, and has undergone the Journal’s usual peer review process.

Applied Physiology Nutrition and Metabolism ◽

10.1139/h09-010 ◽

2009 ◽

Vol 34 (3) ◽

pp. 328-335 ◽

Cited By ~ 38

Author(s):

Espen E. Spangenburg

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Mass ◽

Mechanical Load ◽

Peer Review Process ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Signaling Mechanism ◽

Selection Of

Understanding the mechanisms that regulate skeletal muscle mass has remained a focus of numerous researchers for many years. Recent investigations have begun to elucidate cellular signaling mechanisms that regulate skeletal muscle hypertrophy, with significant effort being focused on the Akt/mammalian target of rapamycin (mTOR) signaling pathway. The Akt/mTOR pathway plays a major role in regulating the initiation of protein synthesis after the onset of mechanical loading of skeletal muscle. Although a number of downstream substrates for Akt/mTOR have been elucidated, very little is known about the upstream mechanisms that mechanical load employs to activate the Akt/mTOR signaling pathway. Thus, the purpose of this review is to discuss potential mechanisms that may contribute to the activation of the Akt/mTOR signaling mechanism in mechanically loaded skeletal muscle.

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mTOR Signaling Pathway Associated With Percent Change In Skeletal Muscle Strength Following Resistance Exercise Training

Medicine & Science in Sports & Exercise ◽

10.1249/01.mss.0000354147.61741.2a ◽

2009 ◽

Vol 41 ◽

pp. 164

Author(s):

Mark A. Newman ◽

Steven E. Riechman ◽

Bret H. Goodpaster ◽

Robert J. Robertson ◽

Fredric L. Goss

Keyword(s):

Skeletal Muscle ◽

Muscle Strength ◽

Exercise Training ◽

Resistance Exercise ◽

Signaling Pathway ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Resistance Exercise Training ◽

Percent Change ◽

Skeletal Muscle Strength

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Down-Regulation of Akt/Mammalian Target of Rapamycin Signaling Pathway in Response to Myostatin Overexpression in Skeletal Muscle

Endocrinology ◽

10.1210/en.2008-0959 ◽

2008 ◽

Vol 150 (1) ◽

pp. 286-294 ◽

Cited By ~ 167

Author(s):

Adel Amirouche ◽

Anne-Cécile Durieux ◽

Sébastien Banzet ◽

Nathalie Koulmann ◽

Régis Bonnefoy ◽

...

Keyword(s):

Skeletal Muscle ◽

Signaling Pathway ◽

Muscle Mass ◽

Protein Metabolism ◽

Skeletal Muscle Mass ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

Gene Electrotransfer ◽

Mtor Signaling Pathway

Myostatin, a member of the TGF-β family, has been identified as a master regulator of embryonic myogenesis and early postnatal skeletal muscle growth. However, cumulative evidence also suggests that alterations in skeletal muscle mass are associated with dysregulation in myostatin expression and that myostatin may contribute to muscle mass loss in adulthood. Two major branches of the Akt pathway are relevant for the regulation of skeletal muscle mass, the Akt/mammalian target of rapamycin (mTOR) pathway, which controls protein synthesis, and the Akt/forkhead box O (FOXO) pathway, which controls protein degradation. Here, we provide further insights into the mechanisms by which myostatin regulates skeletal muscle mass by showing that myostatin negatively regulates Akt/mTOR signaling pathway. Electrotransfer of a myostatin expression vector into the tibialis anterior muscle of Sprague Dawley male rats increased myostatin protein level and decreased skeletal muscle mass 7 d after gene electrotransfer. Using RT-PCR and immunoblot analyses, we showed that myostatin overexpression was ineffective to alter the ubiquitin-proteasome pathway. By contrast, myostatin acted as a negative regulator of Akt/mTOR pathway. This was supported by data showing that the phosphorylation of Akt on Thr308, tuberous sclerosis complex 2 on Thr1462, ribosomal protein S6 on Ser235/236, and 4E-BP1 on Thr37/46 was attenuated 7 d after myostatin gene electrotransfer. The data support the conclusion that Akt/mTOR signaling is a key target that accounts for myostatin function during muscle atrophy, uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle. Myostatin down-regulates Akt/mammalian target of rapamycin (mTOR) signaling pathway uncovering a novel role for myostatin in protein metabolism and more specifically in the regulation of translation in skeletal muscle.

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Targeting mammalian target of rapamycin: prospects for the treatment of inflammatory bowel diseases

Current Medicinal Chemistry ◽

10.2174/0929867327666200504081503 ◽

2020 ◽

Vol 27 ◽

Author(s):

Naser-Aldin Lashgari ◽

Nazanin Momeni Roudsari ◽

Saeideh Momtaz ◽

Negar Ghanaatian ◽

Parichehr Kohansal ◽

...

Keyword(s):

Signaling Pathway ◽

Mammalian Target Of Rapamycin ◽

Mtor Pathway ◽

Mtor Signaling ◽

Target Of Rapamycin ◽

In Vivo Studies ◽

Cochrane Library ◽

Mtor Signaling Pathway ◽

Inflammatory Bowel

: Inflammatory bowel disease (IBD) is a general term for a group of chronic and progressive disorders. Several cellular and biomolecular pathways are implicated in the pathogenesis of IBD, yet the etiology is unclear. Activation of the mammalian target of rapamycin (mTOR) pathway in the intestinal epithelial cells was also shown to induce inflammation. This review focuses on the inhibition of the mTOR signaling pathway and its potential application in treating IBD. We also provide an overview on plant-derived compounds that are beneficial for the IBD management through modulation of the mTOR pathway. Data were extracted from clinical, in vitro and in vivo studies published in English between 1995 and May 2019, which were collected from PubMed, Google Scholar, Scopus and Cochrane library databases. Results of various studies implied that inhibition of the mTOR signaling pathway downregulates the inflammatory processes and cytokines involved in IBD. In this context, a number of natural products might reverse the pathological features of the disease. Furthermore, mTOR provides a novel drug target for IBD. Comprehensive clinical studies are required to confirm the efficacy of mTOR inhibitors in treating IBD.

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Aerobic exercise training decreases cognitive impairment caused by demyelination by regulating ROCK signaling pathway in aging mice

Brain Research Bulletin ◽

10.1016/j.brainresbull.2020.12.010 ◽

2021 ◽

Vol 168 ◽

pp. 52-62

Author(s):

Chuncha Bao ◽

Chengqi He ◽

Bin Shu ◽

Tao Meng ◽

Qiyan Cai ◽

...

Keyword(s):

Cognitive Impairment ◽

Exercise Training ◽

Aerobic Exercise ◽

Signaling Pathway ◽

Aerobic Exercise Training

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Aromadendrin Protects Neuronal Cells from Methamphetamine-Induced Neurotoxicity by Regulating Endoplasmic Reticulum Stress and PI3K/Akt/mTOR Signaling Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms22052274 ◽

2021 ◽

Vol 22 (5) ◽

pp. 2274

Author(s):

Hyun-Su Lee ◽

Eun-Nam Kim ◽

Gil-Saeng Jeong

Keyword(s):

Endoplasmic Reticulum ◽

Er Stress ◽

Signaling Pathway ◽

Neuronal Cells ◽

Mammalian Target Of Rapamycin ◽

Mtor Signaling ◽

Mtor Signaling Pathway ◽

Irreversible Damage ◽

Pre Treatment ◽

Apoptotic Pathways

Methamphetamine (METH) is a highly addictive drug that induces irreversible damage to neuronal cells and pathological malfunction in the brain. Aromadendrin, isolated from the flowers of Chionanthus retusus, has been shown to have anti-inflammatory or anti-tumor activity. Nevertheless, it has been reported that METH exacerbates neurotoxicity by inducing endoplasmic reticulum (ER) stress via the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway in neuronal cells. There is little evidence that aromadendrin protects cells from neurotoxicity induced by METH. In this study, we found that aromadendrin partially suppressed the METH-induced cell death in SH-SY5y cells without causing cytotoxicity. Aromadendrin regulated METH-induced ER stress by preserving the phosphorylation of the PI3K/Akt/mTOR signaling pathway in METH-exposed SH-SY5y cells. In addition, aromadendrin mitigated METH-induced autophagic and the apoptotic pathways in METH-exposed SH-SY5y cells. Mechanistic studies revealed that pre-treatment with aromadendrin restored the expression of anti-apoptotic proteins in METH-exposed conditions. The inhibitor assay confirmed that aromadendrin-mediated restoration of mTOR phosphorylation protected cells from autophagy and apoptosis in METH-exposed cells. Therefore, these findings suggest that aromadendrin relatively has a protective effect on SH-SY5y cells against autophagy and apoptosis induced by METH via regulation of ER stress and the PI3K/Akt/mTOR signaling pathway.

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