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

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.

scholarly journals Sestrin2 as a Potential Target for Regulating Metabolic-Related Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Linan Gong ◽  
Zanzan Wang ◽  
Zhenggui Wang ◽  
Zhiguo Zhang
Keyword(s):  
Er Stress ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Regulatory Relationship ◽  
Alcoholic Fatty Liver

Sestrin2 is a highly conserved protein that can be induced under a variety of stress conditions, including DNA damage, oxidative stress, endoplasmic reticulum (ER) stress, and metabolic stress. Numerous studies have shown that the AMP-activated protein kinase (AMPK)/mammalian target of rapamycin (mTOR) signaling pathway has a crucial role in the regulation of metabolism. Sestrin2 regulates metabolism via a number of pathways, including activation of AMPK, inhibition of the mTOR complex 1 (mTORC1), activation of mTOR complex 2 (mTORC2), inhibition of ER stress, and promotion of autophagy. Therefore, modulation of Sestrin2 activity may provide a potential therapeutic target for the prevention of metabolic diseases such as insulin resistance, diabetes, obesity, non-alcoholic fatty liver disease, and myocardial ischemia/reperfusion injury. In this review, we examined the regulatory relationship between Sestrin2 and the AMPK/mTOR signaling pathway and the effects of Sestrin2 on energy metabolism.

scholarly journals Antidepressants Fluoxetine Mediates Endoplasmic Reticulum Stress and Autophagy of Non-Small Cell Lung Cancer Cells Through ATF4-AKT-Mtor Signaling Pathway.

2021 ◽  
Author(s):  
Shali Shao ◽  
Yajing Du ◽  
Duojiao Wu ◽  
Xiangdong Wang ◽  
Tiankui Qiao
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Signaling Pathway ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Normal Lung ◽  
Mtor Signaling Pathway ◽  
Study Results

Abstract Cancer usually coexists with depression, and depression correspondingly influences the progress and prognosis of cancer. Antidepressants are often used on depression, so it’s meaningful to study how antidepressants affect the cancer. Recently, the antidepressants were reported to have an antiproliferation effect in different cancer. However, the specific molecular target in lung cancer remains unclear. In this study, we investigated how fluoxetine influenced different kind of cells and discovered the molecular basis of its inhibitory effect in lung cancer. CCK8 and immunofluorescence found that fluoxetine specifically inhibited the cell proliferation of H460 and A549 cells and induced autophagy. The analysis of the RNA sequence hinted that the ER stress-related protein and mTOR pathway were involved in the treatment of fluoxetine. Western blot results revealed that fluoxetine activated the endoplasmic reticulum (ER) stress pathway, including PKR-like ER kinase (PERK), activating transcription factor 4 (ATF4), and C/EBP homologous protein (CHOP), while inhibited the AKT/mTOR pathway. In addition, the transfection of ATF4 siRNA further discovered that ER stress participated in the inhibition of the AKT/mTOR pathway and the induction of antiproliferation and autophagy in the fluoxetine-treated cells. More importantly, fluoxetine was demonstrated to play cytotoxic activity in cancer cells without affecting normal cells. Our results showed that fluoxetine triggered the ATF4-AKT-mTOR signaling pathway to induce cell cycle arrest and autophagy to restraint cancer cells growth in lung cancer. This study results found that fluoxetine unaffected the proliferation of normal lung epithelial cells, providing a safe clinical therapeutic strategy for lung cancer patients with depression.

scholarly journals Antidepressants Fluoxetine Mediates Endoplasmic Reticulum Stress and Autophagy of Non-Small Cell Lung Cancer Cells Through ATF4-AKT-mTOR Signaling Pathway.

2021 ◽  
Author(s):  
Shali Shao ◽  
Yajing Du ◽  
Xibing Zhuang ◽  
Tiankui Qiao
Keyword(s):  
Lung Cancer ◽  
Endoplasmic Reticulum ◽  
Er Stress ◽  
Cancer Cells ◽  
Cancer Patients ◽  
Signaling Pathway ◽  
Mtor Pathway ◽  
Mtor Signaling ◽  
Normal Lung ◽  
Mtor Signaling Pathway

Abstract Cancer patients often suffer the depression with worse quality of life and prognosis. Therefore, studying how antidepressants affect the cancer is of great significance. Recent years witnessed the reports that antidepressants have the antiproliferation effect, However, in lung cancer it’s still unclear about the specific molecular target. This study mainly focused on how fluoxetine influenced different types of cells and discovered the molecular basis of its inhibitory effect in lung cancer. The specific antiproliferation effect and autophagy induced by fluoxetine on lung cancer cell were shown in CCK8 and immunofluorescence. The RNA sequence hinted that the endoplasmic reticulum (ER) stress-related protein and mTOR pathway were enriched after fluoxetine treating. Western blot results revealed that the ER stress pathway was activated by fluoxetine, including PERK, ATF4, and CHOP, while the AKT/mTOR pathway was inhibited. In addition, the transfection of ATF4 siRNA further discovered that ER stress participated in the inhibition of AKT/mTOR pathway and the induction of antiproliferation and autophagy in the fluoxetine-treated cells. More importantly, fluoxetine was demonstrated to play cytotoxic activity in cancer cells without affecting normal cells. Our results showed that fluoxetine triggered the ATF4-AKT-mTOR signaling pathway to induce cell cycle arrest and autophagy restraining cancer cells’ growth in lung cancer. This study found fluoxetine unaffected the proliferation of normal lung epithelial cells, providing safe clinical therapeutic strategies for lung cancer patients with depression.

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

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.

scholarly journals Andrographolide enhanced radiosensitivity by downregulating glycolysis via the inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 colorectal cancer cells

2020 ◽  
Vol 48 (8) ◽  
pp. 030006052094616 ◽  
Author(s):  
Xiaofei Li ◽  
Ruifang Tian ◽  
Lan Liu ◽  
Lihui Wang ◽  
Dong He ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Survival ◽  
Signaling Pathway ◽  
Colony Formation ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Glycolytic Activity ◽  
Related Proteins ◽  
Hct116 Cells

Objective Radiotherapy plays an important role in the treatment of colorectal cancer (CRC). However, some patients benefit minimally from radiotherapy because of radioresistance. This study investigated the effects of andrographolide on radiosensitivity in HCT116 CRC cells and examined its mechanism of action. Methods Cell survival, proliferation, apoptosis, and migration were evaluated using MTT, colony formation, flow cytometry, and Transwell cell invasion assays, respectively. Glycolysis-related indicators were measured to examine cell glycolytic activity. The expression of related proteins was detected by western blotting. Results After andrographolide treatment, the expression of phosphoinositide 3-kinase (PI3K)-Akt-mammalian target of rapamycin (mTOR) signaling pathway-related proteins, glycolytic activity, and cell survival and invasion rates were decreased in HCT116 cells. Andrographolide plus irradiation increased apoptosis and decreased survival, invasion, and colony formation compared with the effects of irradiation alone. Conclusion Andrographolide enhanced radiosensitivity by downregulating glycolysis via inhibition of the PI3K-Akt-mTOR signaling pathway in HCT116 cells.

scholarly journals LncRNA GASAL1 Interacts with SRSF1 to Regulate Trophoblast Cell Proliferation, Invasion, and Apoptosis Via the mTOR Signaling Pathway

2020 ◽  
Vol 29 ◽  
pp. 096368972096518
Author(s):  
Jia Liu ◽  
Qing Zhang ◽  
Nan Ma
Keyword(s):  
Cell Proliferation ◽  
Signaling Pathway ◽  
Mammalian Target Of Rapamycin ◽  
Potential Interaction ◽  
Trophoblast Cell ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Promote Cell Proliferation ◽  
Proliferation And Invasion ◽  
Jar Cells

Long noncoding RNAs (lncRNAs) are crucial regulatory molecules involved in diverse biological processes and human diseases, including preeclampsia (PE). The lncRNA growth arrest associated lncRNA 1 (GASAL1) has been implicated in multiple malignant solid tumors and other diseases, while it is poorly known as the potential molecular mechanism of GASAL1 in PE. In this study, GASAL1 was significantly downregulated in the placentas’ of tissues from primipara with PE and trophoblast cell lines. Then, the upregulation of GASAL1 dramatically decreased proliferation and invasion and enhanced apoptosis in HTR-8/SVneo and JAR cells. Bioinformatics tool predicated that there is a potential interaction between GASAL1 and serine/arginine splicing factor 1 (SRSF1). RNA pull-down assays showed that GASAL1 directly binds with SRSF1 that could promote cell proliferation and invasion and suppress cell apoptosis. Further research showed that promoting effects of trophoblasts proliferation and invasion caused by co-transfecting GASAL1 and SRSF1 into HTR-8/SVneo and JAR cells were impaired by SRSF1 knockdown. Moreover, inhibition of the mammalian target of rapamycin (mTOR) activity by rapamycin influenced the effects of GASAL1 on cell proliferation, invasion, and apoptosis. Taken together, these findings suggest that lncRNA GASAL1 interacts with SRSF1 to regulate the proliferative, invasive, and apoptotic abilities of trophoblast cells via the mTOR signaling pathway.

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