signal cascade
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2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Xueqiang Deng ◽  
Xiaowei Fu ◽  
Hong Teng ◽  
Lu Fang ◽  
Bo Liang ◽  
...  

Abstract Background Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear. Methods Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay. Results TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation. Conclusion Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.


2021 ◽  
Author(s):  
Hye Jin Shin ◽  
Keun Bon Ku ◽  
Gun Young Yoon ◽  
Hyun-Woo Moon ◽  
Chonsaeng Kim ◽  
...  

Abstract Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a respiratory pathogen leading to serious multi-organ damage. However, little is known about SARS-CoV-2-induced cellular alterations for understanding robust virus propagation yet. Here we report that SARS-CoV-2 aberrantly elevates mitochondrial bioenergetics and activates epidermal growth factor receptor (EGFR)-mediated cell survival signal cascade for sustaining persistence of SARS-CoV-2. We found that SARS-CoV-2 causes increase in mitochondrial transmembrane potential by SARS-CoV-2 RNA-nucleocapsid cluster, thereby abnormally promoting mitochondrial biogenesis and oxidative phosphorylation (OXPHOS) process followed by abundant ATP production. SARS-CoV-2 also activated EGFR signal cascade and subsequent mitochondrial EGFR accumulation which contributes to the maintenance of abnormal OXPHOS and viral propagation. Therapeutic options for the treatment of COVID-19 are still inadequate. The FDA-approved EGFR inhibitors caused a remarkable reduction in SARS-CoV-2 propagation. Among EGFR inhibitors, vandetanib showing the highest anti-SARS-CoV-2 efficacy exhibited the potent antiviral activity against various SARS-CoV-2 variants including B.1.1.7 (UK variant) and B.1.351 (SA variant) lineages in both in vitro cell culture and in vivo animal experiments using wild-type aged mouse susceptible to SARS-CoV-2 infection, suggesting that EGFR is an attractive host target for combatting COVID-19. Overall, our results suggest that SARS-CoV-2 induces aberrant mitochondrial dynamics and bioenergetics, which significantly contributes to robust SARS-CoV-2 propagation.


2021 ◽  
Author(s):  
Xueqiang Deng ◽  
Xiaowei Fu ◽  
Hong Teng ◽  
Lu Fang ◽  
Bo Liang ◽  
...  

Abstract Background: Pancreatic cancer (PC) is one of the most fatal digestive system cancers. tripartite motif-29 (TRIM29) has been reported as oncogene in several human cancers. However, the precise role and underlying signal cascade of TRIM29 in PC progression remain unclear.Methods: Western blot, qRT-PCR and immunohistochemistry were used to analyze TRIM29 and Yes-associated protein 1 (YAP1) levels. CCK8 assays, EdU assays and flow cytometry were designed to explore the function and potential mechanism of TRIM29 and YAP1 in the proliferation of PC. Next, a nude mouse model of PC was established for validating the roles of TRIM29 and YAP1 in vivo. The relationship among TRIM29 and YAP1 was explored by co-immunoprecipitation and in vitro ubiquitination assay.Results: TRIM29 and YAP1 was significantly upregulated in PC patient samples, and TRIM29 expression was closely related to a malignant phenotype and poorer overall survival (OS) of PC patients. Functional assays revealed that TRIM29 knockdown suppresses cell growth, arrests cell cycle progression and promotes cell apoptosis of PC cells in vivo and in vitro. Furthermore, the rescue experiments demonstrated that TRIM29-induced proliferation is dependent on YAP1 in PC cells. Mechanistically, TRIM29 regulates YAP1 expression by directly binding to YAP1, and reduced its ubiquitination and degradation.Conclusion: Taken together, these results identify a novel mechanism used by PC growth, and provide insight regarding the role of TRIM29 in PC.


2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Gibran Ali ◽  
Mo Zhang ◽  
Runzhen Zhao ◽  
Krishan G. Jain ◽  
Jianjun Chang ◽  
...  
Keyword(s):  

2021 ◽  
Vol 35 ◽  
pp. 205873842110664
Author(s):  
Lobna M Anees ◽  
Gehan R Abdel-Hamid ◽  
Ahmed A Elkady

Background and objective Cisplatin, an effective drug against cancer, commonly induces nephrotoxicity; limiting its therapeutic efficacy and application. In this study, Cisplatin NanoComposite (Cis NC) was formulated successfully from irradiated chitosan coated Cisplatin and MgO nanoparticles (CHIT/Cis/MgO NPs) to promote cisplatin release in a more sustained manner to improve therapeutic efficacy via the reduction of its nephrotoxicity. To compare the relative induced renal toxicity of cisplatin with Cisplatin NanoComposite, histological and biochemical mechanisms underlying nephrotoxicity were investigated. Methods Thirty rats were equally separated to three groups, first group received saline injections and adjusted as the control group, the second group was injected intra-peritoneal with cisplatin 0.64 mg/kg b. wt./day for 6 weeks, the third group was injected intra-peritoneal with Cis NC 5.75 mg/kg b. wt. daily for 6 weeks. Results Cisplatin-induced renal functional impairment and histopathological damages in the kidney; also, cisplatin disrupted the balance of the redox system in renal tissue, stimulated the inflammatory reactions in the kidney via triggering signal transducer and activator of transcription-1 (STAT1) dependent pathways. Moreover, Cisplatin-induced activation of mammalian target of rapamycin mTOR and inactivation of AMPK/PI3K/Akt signal pathway, and was coupled with induction of p53 activity and the executioner caspase3 to induce apoptotic renal cell death. On the other hand, Cis NC exerted a minimal stimulatory effect on apoptotic and inflammatory signal cascade with negligible renal functional and morphological alterations. Conclusion We postulated that Cis NC may be a valued possible drug to decrease the cytotoxicity of cisplatin thus reserves the renal function and structure.


Plants ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 35
Author(s):  
Davide Barreca

The plant kingdom is a rich source of health-promoting compounds and has always played a fundamental role in the isolation, identification, and modification of compounds able to perform several properties on live organisms. Among them, the so-called “antioxidants” have a major potentiality to increase human wellness. Antioxidants are important components in the signaling and defense mechanisms in some plants, where they are precursors of compounds of greater complexity, the modulator of plant growth, and the defensive system against pathogenic organisms and predators. The extraordinary variety of chemical structure and substitution present in the different plant antioxidants make them an inestimable source of interesting compounds, with the ability to counter reactive oxygen/nitrogen species (ROS/RNS) and to stimulate the activation of signal cascade inside the cells. The mechanisms by which antioxidants detoxify these dangerous compounds are complex and involve either direct or indirect interaction with radicals. Antioxidants inhibit or quench free radical reactions mainly based on their reducing capacity or hydrogen atom-donating capacity, their solubility, and chelating properties. Moreover, their ability to modulate key metabolic enzymes and activate/block gene transcription also has remarkable importance.


2020 ◽  
Author(s):  
Elodie Prince ◽  
Jenny Kretzschmar ◽  
Laura C. Trautenberg ◽  
Marko Brankatschk

ABSTRACTThe Insulin signal cascade is one of the best studied metabolic circuits, and shows a remarkable high molecular and functional conservation across the animal kingdom. Insulin-producing cells respond directly to nutritional cues in circulation and receive modulatory input from connected neuronal networks. Neuronal control is rapid and integrates a wide range of variables including dietary change or environmental temperature. However, despite various detailed studies that demonstrated the potential of neuronal regulation the physiological relevance of this circuit remains elusive.In Drosophila, Insulin-like peptide 7 (dIlp7)-producing neurons are wired with Insulin-producing cells. We found a dual role for this neuronal subset: a.) activated dilp7-producing neurons are required to facilitate development at high temperatures, and if confronted with calorie-rich food that represses neuronal activity b.) their product, dIlp7, regulates Insulin signalling levels. Our work shows that Insulin-producing cells not simply integrate signals from circulating nutritional cues and neuronal inputs, but switch to neuronal control in response to dietary composition.


2020 ◽  
Author(s):  
Lin Chen ◽  
Heng Sun ◽  
Jie Kong ◽  
Haijiang Xu ◽  
Xiyan Yang

Abstract BackgroundSoil salt stress seriously restricts the yield and quality of cotton worldwide. To investigate the molecular mechanism of cotton response to salt stress, a main cultivated variety Gossypium hirsutum L. acc. Xinluzhong 54 was used to perform transcriptome and proteome integrated analysis. ResultsThrough transcriptome analysis of cotton treated with salt stress for 0 h (T0), 3 h (T3) and 12 h (T12), we identified 8,436, 11,628 and 6,311 differentially expressed genes (DEGs) inT3 / T0, T12 / T0 and T12 / T3, respectively. A total of 459 differentially expressed proteins (DEPs) were identified by proteomic analysis, of which 273, 99 and 260 DEPs were identified in T3 / T0, T12 / T0 and T12 / T3, respectively. Metabolic pathways, biosynthesis of secondary metabolites, photosynthesis and plant hormone signal transduction were the main enrichment pathways by annotation of DEGs or DEPs. Detail analysis of the DEGs or DEPs revealed that complex signal pathways, such as ABA and JA signal, calcium signal, MAPK signal cascade, transcription factors, followed by activation of antioxidant and ion transporters, were identified to participate in regulating salt response in cotton.ConclusionsOur results not only contribute to understand the mechanism of cotton response to salt stress, but also provide nine candidate genes, which might be used for molecular breeding to improve salt-tolerance in cotton.


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