scholarly journals Silibinin Induced Human Glioblastoma Cell Apoptosis Concomitant with Autophagy through Simultaneous Inhibition of mTOR and YAP

2018 ◽  
Vol 2018 ◽  
pp. 1-10 ◽  
Author(s):  
Zhuan-Li Bai ◽  
Vincent Tay ◽  
Shu-Zhong Guo ◽  
Juan Ren ◽  
Mao-Guo Shu
Keyword(s):  
Cell Apoptosis ◽  
Protein A ◽  
Protective Role ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Downstream Effector ◽  
Simultaneous Inhibition ◽  
Metabolic Activities ◽  
Parp 1

Silibinin, also known as silybin, is the major flavonolignan isolated from Silybum marianum. Although previous reports demonstrated that silibinin exhibits significant tumor suppressor activities in various cancers by promoting cell apoptosis, it was also shown to trigger autophagy to counteract apoptosis induced by exogenous stresses in several types of cells. However, there is no report to address the role of silibinin induced autophagy in human A172 and SR glioblastoma cells. Our study showed that silibinin treatment not only inhibited the metabolic activities of glioblastoma cells but also promoted their apoptosis through the regulation of caspase 3 and PARP-1 in concentration- and time-dependent manners. Meanwhile, silibinin induced autophagy through upregulation of microtubule-associated protein a light chain 3- (LC3-) II. And autophagy inhibition with chloroquine, a lysosomotropic agent, significantly enhanced silibinin induced glioblastoma cell apoptosis. Moreover, silibinin dose-dependently downregulated the phosphorylation levels of mTOR at Ser-2448, p70S6K at Thr-389, and 4E-BP1 at Thr-37/46. Furthermore, the expression of YAP, the downstream effector of Hippo signal pathway, was also suppressed by silibinin. These results suggested that silibinin induced glioblastoma cell apoptosis concomitant with autophagy which might be due to simultaneous inhibition of mTOR and YAP and silibinin induced autophagy exerted a protective role against cell apoptosis in both A172 and SR cells.

Overexpression of miR-431 attenuates hypoxia/reoxygenation-induced myocardial damage via autophagy-related 3

2020 ◽  
Author(s):  
Kang Zhou ◽  
Yan Xu ◽  
Qiong Wang ◽  
Lini Dong
Keyword(s):  
Cell Viability ◽  
Cell Apoptosis ◽  
Myocardial Injury ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Myocardial Damage ◽  
Protective Role ◽  
Human Cardiomyocytes ◽  
Hypoxia Reoxygenation

Abstract Myocardial injury is still a serious condition damaging the public health. Clinically, myocardial injury often leads to cardiac dysfunction and, in severe cases, death. Reperfusion of the ischemic myocardial tissues can minimize acute myocardial infarction (AMI)-induced damage. MicroRNAs are commonly recognized in diverse diseases and are often involved in the development of myocardial ischemia/reperfusion injury. However, the role of miR-431 remains unclear in myocardial injury. In this study, we investigated the underlying mechanisms of miR-431 in the cell apoptosis and autophagy of human cardiomyocytes in hypoxia/reoxygenation (H/R). H/R treatment reduced cell viability, promoted cell apoptotic rate, and down-regulated the expression of miR-431 in human cardiomyocytes. The down-regulation of miR-431 by its inhibitor reduced cell viability and induced cell apoptosis in the human cardiomyocytes. Moreover, miR-431 down-regulated the expression of autophagy-related 3 (ATG3) via targeting the 3ʹ-untranslated region of ATG3. Up-regulated expression of ATG3 by pcDNA3.1-ATG3 reversed the protective role of the overexpression of miR-431 on cell viability and cell apoptosis in H/R-treated human cardiomyocytes. More importantly, H/R treatments promoted autophagy in the human cardiomyocytes, and this effect was greatly alleviated via miR-431-mimic transfection. Our results suggested that miR-431 overexpression attenuated the H/R-induced myocardial damage at least partly through regulating the expression of ATG3.

scholarly journals Congestive heart failure induces endothelial cell apoptosis: protective role of carvedilol

2000 ◽  
Vol 36 (7) ◽  
pp. 2081-2089 ◽  
Author(s):  
Lothar Rössig ◽  
Judith Haendeler ◽  
Ziad Mallat ◽  
Benedicte Hugel ◽  
Jean-Marie Freyssinet ◽  
...  
Keyword(s):  
Heart Failure ◽  
Congestive Heart Failure ◽  
Endothelial Cell ◽  
Cell Apoptosis ◽  
Protective Role ◽  
Endothelial Cell Apoptosis

The protective role of oxymatrine on neuronal cell apoptosis in the hemorrhagic rat brain

2012 ◽  
Vol 143 (1) ◽  
pp. 228-235 ◽  
Author(s):  
Man Huang ◽  
Yue-Yu Hu ◽  
Xiao-Qiao Dong ◽  
Qiu-Ping Xu ◽  
Wen-Hua Yu ◽  
...  
Keyword(s):  
Rat Brain ◽  
Cell Apoptosis ◽  
Neuronal Cell ◽  
Protective Role

scholarly journals VRK1 Depletion Facilitates the Synthetic Lethality of Temozolomide and Olaparib in Glioblastoma Cells

2021 ◽  
Vol 9 ◽  
Author(s):  
Elena Navarro-Carrasco ◽  
Pedro A. Lazo
Keyword(s):  
Dna Damage ◽  
Cell Death ◽  
Tumor Cell ◽  
Dna Damage Response ◽  
Synthetic Lethality ◽  
Glioblastoma Cell ◽  
Glioblastoma Cells ◽  
Tumor Cell Death ◽  
Damage Response ◽  
Parp 1

BackgroundGlioblastomas treated with temozolomide frequently develop resistance to pharmacological treatments. Therefore, there is a need to find alternative drug targets to reduce treatment resistance based on tumor dependencies. A possibility is to target simultaneously two proteins from different DNA-damage repair pathways to facilitate tumor cell death. Therefore, we tested whether targeting the human chromatin kinase VRK1 by RNA interference can identify this protein as a novel molecular target to reduce the dependence on temozolomide in combination with olaparib, based on synthetic lethality.Materials and MethodsDepletion of VRK1, an enzyme that regulates chromatin dynamic reorganization and facilitates resistance to DNA damage, was performed in glioblastoma cells treated with temozolomide, an alkylating agent used for GBM treatment; and olaparib, an inhibitor of PARP-1, used as sensitizer. Two genetically different human glioblastoma cell lines, LN-18 and LN-229, were used for these experiments. The effect on the DNA-damage response was followed by determination of sequential steps in this process: H4K16ac, γH2AX, H4K20me2, and 53BP1.ResultsThe combination of temozolomide and olaparib increased DNA damage detected by labeling free DNA ends, and chromatin relaxation detected by H4K16ac. The combination of both drugs, at lower doses, resulted in an increase in the DNA damage response detected by the formation of γH2AX and 53BP1 foci. VRK1 depletion did not prevent the generation of DNA damage in TUNEL assays, but significantly impaired the DNA damage response induced by temozolomide and olaparib, and mediated by γH2AX, H4K20me2, and 53BP1. The combination of these drugs in VRK1 depleted cells resulted in an increase of glioblastoma cell death detected by annexin V and the processing of PARP-1 and caspase-3.ConclusionDepletion of the chromatin kinase VRK1 promotes tumor cell death at lower doses of a combination of temozolomide and olaparib treatments, and can be a novel alternative target for therapies based on synthetic lethality.

Fluidizing effects of C‐reactive protein on lung surfactant membranes: protective role of surfactant protein A

2010 ◽  
Vol 24 (10) ◽  
pp. 3662-3673 ◽  
Author(s):  
Alejandra Saenz ◽  
Almudena López‐Sánchez ◽  
Jonás Mojica‐Lázaro ◽  
Leticia Martínez‐Caro ◽  
Nicolas Nin ◽  
...  
Keyword(s):  
Lung Surfactant ◽  
Protein A ◽  
Surfactant Protein ◽  
Protective Role ◽  
Surfactant Protein A ◽  
C Reactive Protein ◽  
Reactive Protein

scholarly journals A2BAR activation attenuates acute lung injury by inhibiting alveolar epithelial cell apoptosis both in vivo and in vitro

2018 ◽  
Vol 315 (4) ◽  
pp. C558-C570 ◽  
Author(s):  
Xiaotao Xu ◽  
Qingwei Zhu ◽  
Fangfang Niu ◽  
Rong Zhang ◽  
Yan Wang ◽  
...  
Keyword(s):  
Acute Lung Injury ◽  
Lung Injury ◽  
Cell Apoptosis ◽  
A549 Cells ◽  
Apoptosis Pathway ◽  
Alveolar Epithelial ◽  
Exact Function ◽  
Parp 1

The epithelial barrier of the lung is destroyed during acute lung injury (ALI)/acute respiratory distress syndrome (ARDS) due to the apoptosis of alveolar epithelial cells (AECs). Therefore, treatments that block AEC apoptosis might be a therapeutic strategy to ameliorate ALI. Based on recent evidence, A2B adenosine receptor (A2BAR) plays an important role in ALI in several different animal models, but its exact function in AECs has not been clarified. We investigated the role of A2BAR in AEC apoptosis in a mouse model of oleic acid (OA)-induced ALI and in hydrogen peroxide (H2O2)-induced AEC (A549 cells and MLE-12 cells) injury. Mice treated with BAY60-6583, a selective A2BAR agonist, showed lower AEC apoptosis rates than mice treated with OA. However, the role of BAY60-6583 in OA-induced ALI was attenuated by a specific blocker of A2BAR, PSB1115. A2BAR activation decreased H2O2-induced cell apoptosis in vitro, as characterized by the translocation of apoptotic proteins, the release of cytochrome c, and the activation of caspase-3 and poly (ADP ribose) polymerase 1 (PARP-1). In addition, apoptosis was required for the phosphorylation of ERK1/2, p38, and JNK. Importantly, compared with cells transfected with the A2BAR-siRNA, an ERK inhibitor or p38 inhibitor exhibited decreased apoptotic ratios and cleaved caspase-9 and cleaved PARP-1 levels, whereas the JNK inhibitor displayed increases in these parameters. In conclusion, A2BAR activation effectively attenuated OA-induced ALI by inhibiting AEC apoptosis and mitigated H2O2-induced AEC injury by suppressing the p38 and ERK1/2-mediated mitochondrial apoptosis pathway.

scholarly journals Protective Role of Complement C3 Against Cytokine-Mediated β-Cell Apoptosis

Endocrinology ◽  
2017 ◽  
Vol 158 (8) ◽  
pp. 2503-2521 ◽  
Author(s):  
Reinaldo S Dos Santos ◽  
Laura Marroqui ◽  
Fabio A Grieco ◽  
Lorella Marselli ◽  
Mara Suleiman ◽  
...  
Keyword(s):  
Cell Apoptosis ◽  
Protective Role ◽  
Complement C3 ◽  
Β Cell

scholarly journals IL-37b alleviates endothelial cell apoptosis and inflammation in Kawasaki disease through IL-1R8 pathway

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Chang Jia ◽  
Yingzhi Zhuge ◽  
Shuchi Zhang ◽  
Chao Ni ◽  
Linlin Wang ◽  
...  
Keyword(s):  
Endothelial Cell ◽  
Kawasaki Disease ◽  
Mouse Model ◽  
Cell Apoptosis ◽  
Developed Countries ◽  
Protective Role ◽  
Potential Candidate ◽  
Endothelial Cell Apoptosis ◽  
Apoptosis And Inflammation

AbstractKawasaki disease (KD) is an acute vasculitis of pediatric populations that may develop coronary artery aneurysms if untreated. It has been regarded as the principal cause of acquired heart disease in children of the developed countries. Interleukin (IL)-37, as one of the IL-1 family members, is a natural suppressor of inflammation that is caused by activation of innate and adaptive immunity. However, detailed roles of IL-37 in KD are largely unclear. Sera from patients with KD displayed that IL-37 level was significantly decreased compared with healthy controls (HCs). QRT-PCR and western blot analyses showed that the expression level of IL-37 variant, IL-37b, was remarkably downregulated in human umbilical vein endothelial cells (HUVECs) exposed to KD sera-treated THP1 cells. Therefore, we researched the role of IL-37b in the context of KD and hypothesized that IL-37b may have a powerful protective effect in KD patients. We first observed and substantiated the protective role of IL-37b in a mouse model of KD induced by Candida albicans cell wall extracts (CAWS). In vitro experiments demonstrated that IL-37b alleviated endothelial cell apoptosis and inflammation via IL-1R8 receptor by inhibiting ERK and NFκB activation, which were also recapitulated in the KD mouse model. Together, our findings suggest that IL-37b play an effective protective role in coronary endothelial damage in KD, providing new evidence that IL-37b is a potential candidate drug to treat KD.

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