scholarly journals Fast-Acting and Receptor-Mediated Regulation of Neuronal Signaling Pathways by Copaiba Essential Oil

2020 ◽  
Vol 21 (7) ◽  
pp. 2259 ◽  
Author(s):  
Yasuyo Urasaki ◽  
Cody Beaumont ◽  
Michelle Workman ◽  
Jeffery N. Talbot ◽  
David K. Hill ◽  
...  
Keyword(s):  
Essential Oil ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cannabinoid Receptor ◽  
Biological Activities ◽  
Chemical Constituents ◽  
Neuronal Cell ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Fast Acting

This study examined the biological activities of copaiba essential oil via measurement of its effects on signaling pathways in the SH-SY5Y neuronal cell line. Nanofluidic proteomic technologies were deployed to measure the phosphorylation of biomarker proteins within the signaling cascades. Interestingly, copaiba essential oil upregulated the pI3K/Akt/mTOR, MAPK, and JAK/STAT signaling pathways in neuronal cells. The effects of copaiba essential oil peaked at 30 min post-treatment, with a half-maximal effective concentration (EC50) of approximately 80 ng/mL. Treatment with cannabinoid receptor 2 (CB2) agonist AM1241 or the inverse agonist BML190 abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Surprisingly, copaiba essential oil also activated the apoptosis signaling pathway and reduced the viability of SH-SY5Y cells with an EC50 of approximately 400 ng/mL. Furthermore, β-caryophyllene, a principal constituent of copaiba essential oil, downregulated the pI3K/Akt/mTOR signaling pathway. Taken together, the findings indicated that copaiba essential oil upregulated signaling pathways associated with cell metabolism, growth, immunity, and apoptosis. The biological activities of copaiba essential oil were determined to be fast acting, CB2 mediated, and dependent on multiple chemical constituents of the oil. Nanofluidic proteomics provided a powerful means to assess the biological activities of copaiba essential oil.

scholarly journals Akt3 Regulates the Tissue-Specific Response to Copaiba Essential Oil

2020 ◽  
Vol 21 (8) ◽  
pp. 2851
Author(s):  
Yasuyo Urasaki ◽  
Cody Beaumont ◽  
Jeffery N. Talbot ◽  
David K. Hill ◽  
Thuc T. Le
Keyword(s):  
Essential Oil ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Liver Cells ◽  
Mtor Signaling ◽  
Specific Response ◽  
Mtor Signaling Pathway ◽  
Tissue Specific ◽  
Regulatory Effects ◽  
Specific Regulation

This study reports a relationship between Akt3 expression and tissue-specific regulation of the pI3K/Akt/mTOR signaling pathway by copaiba essential oil. Akt3, a protein kinase B isoform important for the regulation of neuronal development, exhibited differential expression levels in cells of various origins. In neuronal and microglial cells, where Akt3 is present, copaiba essential oil positively regulated the pI3K/Akt/mTOR signaling pathway. In contrast, in liver cells and T lymphocytes, where Akt3 is absent, copaiba essential oil negatively regulated the pI3K/Akt/mTOR signaling pathway. The expression of Akt3 via plasmid DNA in liver cells led to positive regulatory effects by copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. In contrast, inhibition of Akt3 expression in neuronal cells via small interfering RNA molecules targeting Akt3 transcripts abrogated the regulatory effects of copaiba essential oil on the pI3K/Akt/mTOR signaling pathway. Interestingly, Akt3 expression did not impact the regulatory effects of copaiba essential oil on other signaling pathways. For example, copaiba essential oil consistently upregulated the MAPK and JAK/STAT signaling pathways in all evaluated cell types, independent of the Akt3 expression level. Collectively, the data indicated that Akt3 expression was required for the positive regulatory effects of copaiba essential oil, specifically on the pI3K/Akt/mTOR signaling pathway.

scholarly journals Chlorogenic acid protects PC12 cells against corticosterone-induced neurotoxicity related to inhibition of autophagy and apoptosis

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Xiaowen Shi ◽  
Nian Zhou ◽  
Jieyi Cheng ◽  
Xunlong Shi ◽  
Hai Huang ◽  
...  
Keyword(s):  
Cell Viability ◽  
Chlorogenic Acid ◽  
Signaling Pathway ◽  
Pc12 Cells ◽  
Molecular Mechanism ◽  
Cell Activity ◽  
Neuronal Cell ◽  
Mtor Signaling ◽  
Specific Marker ◽  
Mtor Signaling Pathway

Abstract Background There are evidences that chlorogenic acid (CGA) has antidepressant effects, however the underlying molecular mechanism has not been well understood. The aim of the study was to explore the neuroprotective effect of CGA on corticosterone (CORT)-induced PC 12 cells and its mechanism, especially the autophagy pathway. Methods PC12 cells were incubated with CORT (0, 100, 200, 400 or 800 μM) for 24 h, cell viability was measured by MTT assay. PC12 cells were cultured with 400 μM of CORT in the absence or presence of CGA (25 μg/ml) for 24 h, morphologies and specific marker of autophagosome were observed by transmission electron microscope (TEM) and confocal immunofluorescence microscopy, respectively. In addition, PC12 cells were treated with different doses of CGA (0, 6.25, 12.5, 25 or 50 μg/ml) with or without CORT (400 μM) for 24 h, cell viability and changes in the morphology were observed, and further analysis of apoptotic and autophagic proteins, and expression of AKT/mTOR signaling pathway were carried out by Western blot. Specific inhibitors of autophagy 3-Methyladenine (3-MA) and chloroquine (CQ) were added to the PC12 cells cultures to explore the potential role of autophagy in CORT-induced neuronal cell apoptosis. Results Besides decreasing PC12 cell activity, CORT could also induce autophagy and apoptosis of PC12 cells, while CGA could reverse these effects. In addition, CGA treatment regulated AKT/mTOR signaling pathway in PC12 cells. CGA, similar to 3-MA and QC, significantly inhibited CORT-induced apoptosis in PC12 cells. Conclusions Our results provide a new molecular mechanism for the treatment of CORT-induced neurotoxicity by CGA, and suggest CGA may be a potential substance which is can alleviate depression.

scholarly journals Melatonin induces the rejuvenation of long-term ex vivo expanded periodontal ligament stem cells by modulating the autophagic process

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Yi-Zhou Tan ◽  
Xin-Yue Xu ◽  
Ji-Min Dai ◽  
Yuan Yin ◽  
Xiao-Tao He ◽  
...  
Keyword(s):  
Stem Cells ◽  
Signaling Pathways ◽  
Signaling Pathway ◽  
Cellular Senescence ◽  
Periodontal Ligament ◽  
Ex Vivo ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Periodontal Ligament Stem Cells

Abstract Background Stem cells that have undergone long-term ex vivo expansion are most likely functionally compromised (namely cellular senescence) in terms of their stem cell properties and therapeutic potential. Due to its ability to attenuate cellular senescence, melatonin (MLT) has been proposed as an adjuvant in long-term cell expansion protocols, but the mechanism underlying MLT-induced cell rejuvenation remains largely unknown. Methods Human periodontal ligament stem cells (PDLSCs) were isolated and cultured ex vivo for up to 15 passages, and cells from passages 2, 7, and 15 (P2, P7, and P15) were used to investigate cellular senescence and autophagy change in response to long-term expansion and indeed the following MLT treatment. Next, we examined whether MLT could induce cell rejuvenation by restoring the autophagic processes of damaged cells and explored the underlying signaling pathways. In this context, cellular senescence was indicated by senescence-associated β-galactosidase (SA-β-gal) activity and by the expression of senescence-related proteins, including p53, p21, p16, and γ-H2AX. In parallel, cell autophagic processes were evaluated by examining autophagic vesicles (by transmission electronic microscopy), autophagic flux (by assessing mRFP-GFP-LC3-transfected cells), and autophagy-associated proteins (by Western blot assay of Atg7, Beclin-1, LC3-II, and p62). Results We found that long-term in vitro passaging led to cell senescence along with impaired autophagy. As expected, MLT supplementation not only restored cells to a younger state but also restored autophagy in senescent cells. Additionally, we demonstrated that autophagy inhibitors could block MLT-induced cell rejuvenation. When the underlying signaling pathways involved were investigated, we found that the MLT receptor (MT) mediated MLT-related autophagy restoration by regulating the PI3K/AKT/mTOR signaling pathway. Conclusions The present study suggests that MLT may attenuate long-term expansion-caused cellular senescence by restoring autophagy, most likely via the PI3K/AKT/mTOR signaling pathway in an MT-dependent manner. This is the first report identifying the involvement of MT-dependent PI3K/AKT/mTOR signaling in MLT-induced autophagy alteration, indicating a potential of autophagy-restoring agents such as MLT to be used in the development of optimized clinical-scale cell production protocols.

DUXAP8: a promising lncRNA with carcinogenic potential in cancer

2021 ◽  
Vol 28 ◽  
Author(s):  
Bei Wang ◽  
Wen Xu ◽  
Yuxuan Cai ◽  
Jinlan Chen ◽  
Chong Guo ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Therapeutic Target ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway ◽  
Over Expression ◽  
Significant Potential ◽  
Carcinogenic Potential ◽  
Treatment Plans ◽  
Non Coding Rnas

Background: Long non-coding RNAs (lncRNA) have influenced numerous biology processes, which has provoked great interest. Not only that, LncRNA DUXAP8 mediates tumorigenesis by affecting the activity of miRNAs, signaling pathways, and oncogene. Methods: The functions of DUXAP8 have been summarized by reading relevant articles on PubMed. Results: lncRNA DUXAP8 acts oncogene in most tumors. The abnormal over-expression is associated with the proliferation, invasion, migration, anti-autophagy of tumors. DUXAP8 exerts promotion on Akt / mTOR signaling pathway, facilitating the occurrence of tumors. Furthermore, DUXAP8 affects the activity of miRNAs and proteins, showing its significant potential as a therapeutic target in human cancers. Conclusion: LncRNA DUXAP8 has been identified as an indispensable therapeutic target of the tumors, providing clinical treatment plans.

scholarly journals A Novel lnc-RNA, Named lnc-ORA, Is Identified by RNA-Seq Analysis, and Its Knockdown Inhibits Adipogenesis by Regulating the PI3K/AKT/mTOR Signaling Pathway

Cells ◽  
2019 ◽  
Vol 8 (5) ◽  
pp. 477 ◽  
Author(s):  
Rui Cai ◽  
Guorong Tang ◽  
Que Zhang ◽  
Wenlong Yong ◽  
Wanrong Zhang ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Expression Profiles ◽  
Enrichment Analysis ◽  
Mtor Signaling ◽  
Receptor Interaction ◽  
Rna Seq ◽  
Mtor Signaling Pathway ◽  
Mrna And Protein Expression

Obesity is closely associated with numerous adipogenic regulatory factors, including coding and non-coding genes. Long noncoding RNAs (lncRNAs) play a major role in adipogenesis. However, differential expression profiles of lncRNAs in inguinal white adipose tissue (iWAT) between wild-type (WT) and ob/ob mice, as well as their roles in adipogenesis, are not well understood. Here, a total of 2809 lncRNAs were detected in the iWAT of WT and ob/ob mice by RNA-Sequencing (RNA-Seq), including 248 novel lncRNAs. Of them, 46 lncRNAs were expressed differentially in WT and ob/ob mice and were enriched in adipogenesis signaling pathways as determined by KEGG enrichment analysis, including the PI3K/AKT/mTOR and cytokine–cytokine receptor interaction signaling pathways. Furthermore, we focused on one novel lncRNA, which we named lnc-ORA (obesity-related lncRNA), which had a seven-fold higher expression in ob/ob mice than in WT mice. Knockdown of lnc-ORA inhibited preadipocyte proliferation by decreasing the mRNA and protein expression levels of cell cycle markers. Interestingly, lnc-ORA knockdown inhibited adipocyte differentiation by regulating the PI3K/AKT/mTOR signaling pathway. In summary, these findings contribute to a better understanding of adipogenesis in relation to lncRNAs and provide novel potential therapeutic targets for obesity-related metabolic diseases.

scholarly journals Potency Assessment of CBD Oils by Their Effects on Cell Signaling Pathways

Nutrients ◽  
2020 ◽  
Vol 12 (2) ◽  
pp. 357 ◽  
Author(s):  
Yasuyo Urasaki ◽  
Cody Beaumont ◽  
Michelle Workman ◽  
Jeffery N. Talbot ◽  
David K. Hill ◽  
...  
Keyword(s):  
Signaling Pathways ◽  
Posttranslational Modification ◽  
Biological Activities ◽  
Neuronal Cell ◽  
Effective Concentration ◽  
Composition Analysis ◽  
Measurable Effect ◽  
Mtor Signaling Pathway ◽  
Chemical Composition Analysis ◽  
Cell Signaling Pathways

This study used nanofluidic protein posttranslational modification (PTM) profiling to measure the effects of six cannabidiol (CBD) oils and isolated CBD on the signaling pathways of a cultured SH-SY5Y neuronal cell line. Chemical composition analysis revealed that all CBD oils met the label claims and legal regulatory limit regarding the CBD and tetrahydrocannabinol (THC) contents, respectively. Isolated CBD was cytotoxic, with an effective concentration (EC50) of 40 µM. In contrast, the CBD oils had no effect on cell viability at CBD concentrations exceeding 1.2 mM. Interestingly, only an unadulterated CBD oil had strong and statistically significant suppressive effects on the pI3K/Akt/mTOR signaling pathway with an EC50 value of 143 µM and a slow-acting timescale requiring hours. Systematic profiling of twenty-six proteins, which served as biomarkers for nine signaling pathways, revealed that the unadulterated CBD oil downregulated seven signaling pathways but had no measurable effect on the other two signaling pathways. The remaining CBD oils, which were adulterated, and isolated CBD had weak, variable, or undetectable effects on neuronal signaling pathways. Our data clearly showed that adulteration diminished the biological activities of CBD oils. In addition, nanofluidic protein PTM profiling provided a robust means for potency assessment of CBD oils.

UPF1 Impacts on mTOR Signaling Pathway and Autophagy in Endometrioid Endometrial Carcinoma

2020 ◽  
Author(s):  
Minfen Zhang ◽  
Hui Chen ◽  
Ping Qin ◽  
Tonghui Cai ◽  
Lingjun Li ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Mtor Signaling ◽  
Mtor Signaling Pathway

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.

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