scholarly journals Photothermal treatment of liver cancer with albumin-conjugated gold nanoparticles initiates Golgi Apparatus–ER dysfunction and caspase-3 apoptotic pathway activation by selective targeting of Gp60 receptor

2015 ◽  
pp. 5435 ◽  
Author(s):  
Cornel Iancu ◽  
Teodora Mocan ◽  
Lucian Mocan ◽  
Cristian Matea ◽  
Flaviu Tabaran ◽  
...  
Keyword(s):  
Gold Nanoparticles ◽  
Liver Cancer ◽  
Golgi Apparatus ◽  
Caspase 3 ◽  
Apoptotic Pathway ◽  
Photothermal Treatment ◽  
Pathway Activation ◽  
Selective Targeting

Effect of redox imbalance on protein modifications in lymphocytes of psoriatic patients

2019 ◽  
Vol 167 (3) ◽  
pp. 323-331 ◽  
Author(s):  
Piotr Wójcik ◽  
Agnieszka Gęgotek ◽  
Adam Wroński ◽  
Anna Jastrząb ◽  
Agnieszka Żebrowska ◽  
...  
Keyword(s):  
Metabolic Pathways ◽  
Caspase 3 ◽  
Psoriasis Vulgaris ◽  
Redox Status ◽  
Redox Activity ◽  
Apoptotic Pathway ◽  
Protein Modifications ◽  
Redox Imbalance ◽  
Pathway Activation ◽  
Enhanced Expression

Abstract Lymphocytes are one of the most important cells involved in the pathophysiology of psoriasis; therefore, the aim of this study was to assess the redox imbalance and protein modifications in the lymphocytes of patients with psoriasis vulgaris (PsV) or psoriatic arthritis (PsA). The results show a stronger shift in redox status to pro-oxidative conditions (observed as an increased reactive oxygen species level, a decrease in catalase activity and lower levels of glutathione peroxidase and vitamin E compared with healthy controls) in the lymphocytes of PsA than PsV patients. It is also favoured by the enhanced level of activators of the Nrf2 transcription factor in lymphocytes of PsV compared with decreased of these proteins level in PsA. Moreover, the differential modifications of proteins by lipid peroxidation products 4-oxononenal (mainly binding proteins) and malondialdehyde (mainly catalytic proteins with redox activity), promoted a pro-apoptotic pathway in lymphocytes of PsV, which was manifested by enhanced expression of pro-apoptotic caspases, particularly caspase 3. Taken together, differences in Nrf2 pathway activation may be responsible for the differential level of redox imbalance in lymphocytes of patients with PsV and PsA. This finding may enable identification of a targeted therapy to modify the metabolic pathways disturbed in psoriasis.

scholarly journals Apoptotic pathway activation from mitochondria and death receptors without caspase-3 cleavage in failing human myocardium

2002 ◽  
Vol 39 (3) ◽  
pp. 481-488 ◽  
Author(s):  
Robert J Scheubel ◽  
Babett Bartling ◽  
Andreas Simm ◽  
Rolf-Edgar Silber ◽  
Kostas Drogaris ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Death Receptors ◽  
Human Myocardium ◽  
Apoptotic Pathway ◽  
Pathway Activation

scholarly journals ClC-5 Downregulation Induces Osteosarcoma Cell Apoptosis by Promoting Bax and tBid Complex Formation

2021 ◽  
Vol 10 ◽  
Author(s):  
Fei Peng ◽  
Weisong Cai ◽  
Jianping Li ◽  
Haohuan Li
Keyword(s):  
Complex Formation ◽  
Cell Apoptosis ◽  
Caspase 3 ◽  
Osteosarcoma Cell ◽  
Osteosarcoma Cells ◽  
Caspase 9 ◽  
Poor Overall Survival ◽  
Apoptotic Pathway ◽  
Normal Bone ◽  
Pathway Activation

Osteosarcoma is the most common malignant bone tumor. Chloride (Cl−) channels-mediated Cl− movement plays an important role in regulating the functions of various cancer cells, but its role in osteosarcoma remains unclear. In this study, we found that ClC-5 was increased in osteosarcoma tissues compared with normal bone tissues. Patients with high ClC-5 expression showed poor overall survival relative to those patients with low ClC-5 expression. Higher ClC-5 expression and lower intracellular Cl− concentration ([Cl−]i) were observed in osteosarcoma cells compared with normal osteoblasts. Lowering [Cl−]i increased the viability of osteosarcoma cells, which was markedly blocked by ClC-5 downregulation. Knockdown of ClC-5 significantly induced osteosarcoma cell apoptosis and increased the release of cytochrome c from mitochondria to cytosol, concomitantly with cleavage of caspase-9, caspase-3, and PARP. The effect of ClC-5 downregulation on osteosarcoma cell apoptosis and viability was abolished by caspase-3 and caspase-9 inhibitors, but not caspase-8 inhibitor. Furthermore, ClC-5 inhibition promoted Bax translocation from cytosol to mitochondria. Immunoprecipitation showed that ClC-5 interacted with Bax and ClC-5 downregulation enhanced Bax and tBid complex formation. Collectively, we demonstrate that ClC-5 downregulation induces osteosarcoma cell apoptosis via mitochondria-dependent apoptotic pathway activation by promoting Bax and tBid association and subsequent Bax translocation.

Gold nanoparticles application in liver cancer

2019 ◽  
Vol 25 ◽  
pp. 389-400 ◽  
Author(s):  
Saeed Taghizadeh ◽  
Vahid Alimardani ◽  
Parvin Lohrasbi Roudbali ◽  
Younes Ghasemi ◽  
Elina Kaviani
Keyword(s):  
Gold Nanoparticles ◽  
Liver Cancer

scholarly journals trans-Fatty acids promote p53-dependent apoptosis triggered by cisplatin-induced DNA interstrand crosslinks via the Nox-RIP1-ASK1-MAPK pathway

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yusuke Hirata ◽  
Miki Takahashi ◽  
Yuto Yamada ◽  
Ryosuke Matsui ◽  
Aya Inoue ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Mapk Pathway ◽  
Regulatory Protein ◽  
Strand Break ◽  
Mitogen Activated Protein Kinase ◽  
Ros Generation ◽  
Apoptotic Pathway ◽  
Interstrand Crosslinks ◽  
Pathway Activation ◽  
Dna Interstrand Crosslinks

Abstracttrans-Fatty acids (TFAs) are food-derived fatty acids associated with various diseases including cardiovascular diseases. However, the underlying etiology is poorly understood. Here, we show a pro-apoptotic mechanism of TFAs such as elaidic acid (EA), in response to DNA interstrand crosslinks (ICLs) induced by cisplatin (CDDP). We previously reported that TFAs promote apoptosis induced by doxorubicin (Dox), a double strand break (DSB)-inducing agent, via a non-canonical apoptotic pathway independent of tumor suppressor p53 and apoptosis signal-regulating kinase (ASK1), a reactive oxygen species (ROS)-responsive kinase. However, here we found that in the case of CDDP-induced apoptosis, EA-mediated pro-apoptotic action was reversed by knockout of either p53 or ASK1, despite no increase in p53 apoptotic activity. Upon CDDP treatment, EA predominantly enhanced ROS generation, ASK1-p38/c-Jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) pathway activation, and ultimately cell death, all of which were suppressed either by co-treatment of the NADPH oxidase (Nox) inhibitor Apocynin, or by knocking out its regulatory protein, receptor-interacting protein 1 (RIP1). These results demonstrate that in response to CDDP ICLs, TFAs promote p53-dependent apoptosis through the enhancement of the Nox-RIP1-ASK1-MAPK pathway activation, providing insight into the diverse pathogenetic mechanisms of TFAs according to the types of DNA damage.

scholarly journals 20-HETE-mediated cytotoxicity and apoptosis in ischemic kidney epithelial cells

2008 ◽  
Vol 294 (3) ◽  
pp. F562-F570 ◽  
Author(s):  
Vani Nilakantan ◽  
Cheryl Maenpaa ◽  
Guangfu Jia ◽  
Richard J. Roman ◽  
Frank Park
Keyword(s):  
Caspase 3 ◽  
Fluorescent Protein ◽  
Ischemia Reperfusion ◽  
Atp Depletion ◽  
Cellular Damage ◽  
Apoptotic Pathway ◽  
Injury Model ◽  
Green Fluorescent

20-HETE, a metabolite of arachidonic acid, has been implicated as a mediator of free radical formation and tissue death following ischemia-reperfusion (IR) injury in the brain and heart. The present study examined the role of this pathway in a simulated IR renal injury model in vitro. Modified self-inactivating lentiviral vectors were generated to stably overexpress murine Cyp4a12 following transduction into LLC-PK1 cells (LLC-Cyp4a12). We compared the survival of control and transduced LLC-PK1 cells following 4 h of ATP depletion and 2 h of recovery in serum-free medium. ATP depletion-recovery of LLC-Cyp4a12 cells resulted in a significantly higher LDH release ( P < 0.05) compared with LLC-enhanced green fluorescent protein (EGFP) cells. Treatment with the SOD mimetic MnTMPyP (100 μM) resulted in decreased cytotoxicity in LLC-Cyp4a12 cells. The selective 20-HETE inhibitor HET-0016 (10 μM) also inhibited cytotoxicity significantly ( P < 0.05) in LLC-Cyp4a12 cells. Dihydroethidium fluorescence showed that superoxide levels were increased to the same degree in LLC-EGFP and LLC-Cyp4a12 cells after ATP depletion-recovery compared with control cells and that this increase was inhibited by MnTMPyP. There was a significant increase ( P < 0.05) of caspase-3 cleavage, an effector protease of the apoptotic pathway, in the LLC-Cyp4a12 vs. LLC-EGFP cells ( P < 0.05). This was abolished in the presence of HET-0016 ( P < 0.05) or MnTMPyP ( P < 0.01). These results demonstrate that 20-HETE overexpression can significantly exacerbate the cellular damage that is associated with renal IR injury and that the programmed cell death is mediated by activation of caspase-3 and is partially dependent on enhanced CYP4A generation of free radicals.

Role of protein kinase C-η in cigarette smoke extract-induced apoptosis in MRC-5-cells

2014 ◽  
Vol 34 (9) ◽  
pp. 869-877 ◽  
Author(s):  
ES Son ◽  
SY Kyung ◽  
SP Lee ◽  
SH Jeong ◽  
JY Shin ◽  
...  
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Cigarette Smoke ◽  
Caspase 3 ◽  
Dominant Negative ◽  
Lung Fibroblasts ◽  
Apoptotic Pathway ◽  
Kinase C ◽  
Extrinsic Apoptotic Pathway ◽  
Infected Cells

Cigarette smoke (CS) is a major risk factor for emphysema, which causes cell death in structural cells of the lung by mechanisms that are still not completely understood. We demonstrated previously that CS extract (CSE) induces caspase activation in MRC-5 human lung fibroblasts, activated protein kinase C-η (PKC-η), and translocated PKC-η from the cytosol to the membrane. The objective of this study was to investigate the involvement of PKC-η activation in a CSE-induced extrinsic apoptotic pathway. We determined that CSE increases expression of caspase 3 and 8 cleavage in MRC-5 cells and overexpression of PKC-η significantly increased expression of caspase 3 and 8 cleavage compared with control LacZ-infected cells. In contrast, dominant negative (dn) PKC-η inhibited apoptosis in MRC-5 cells exposed to CSE and decreased expression of caspase 3 and 8 compared with control cells. Exposure to 10% CSE for >8 h significantly increased lactate dehydrogenase release in PKC-η-infected cells compared with LacZ-infected cells. Additionally, PKC-η-infected cells had an increased number of Hoechst 33342 stained nuclei compared with LacZ-infected cells, while dn PKC-η-infected cells exhibited fewer morphological changes than LacZ-infected cells under phase-contrast microscopy. In conclusion, PKC-η activation plays a pro-apoptotic role in CSE-induced extrinsic apoptotic pathway in MRC-5 cells. These results suggest that modulation of PKC-η may be a useful tool for regulating the extrinsic apoptosis of MRC-5 cells by CSE and may have therapeutic potential in the treatment of CS-induced lung injury.

scholarly journals Phylogenetic analysis of the caspase family in bivalves: implications for programmed cell death, immune response and development

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Susanne Vogeler ◽  
Stefano Carboni ◽  
Xiaoxu Li ◽  
Alyssa Joyce
Keyword(s):  
Immune Response ◽  
Caspase 3 ◽  
Developmental Stages ◽  
Phylogenetic Analyses ◽  
Apoptotic Pathway ◽  
Caspase Family ◽  
Executioner Caspases ◽  
And Function ◽  
Relationship Of ◽  
Inflammatory Caspases

Abstract Background Apoptosis is an important process for an organism’s innate immune system to respond to pathogens, while also allowing for cell differentiation and other essential life functions. Caspases are one of the key protease enzymes involved in the apoptotic process, however there is currently a very limited understanding of bivalve caspase diversity and function. Results In this work, we investigated the presence of caspase homologues using a combination of bioinformatics and phylogenetic analyses. We blasted the Crassostrea gigas genome for caspase homologues and identified 35 potential homologues in the addition to the already cloned 23 bivalve caspases. As such, we present information about the phylogenetic relationship of all identified bivalve caspases in relation to their homology to well-established vertebrate and invertebrate caspases. Our results reveal unexpected novelty and complexity in the bivalve caspase family. Notably, we were unable to identify direct homologues to the initiator caspase-9, a key-caspase in the vertebrate apoptotic pathway, inflammatory caspases (caspase-1, − 4 or − 5) or executioner caspases-3, − 6, − 7. We also explored the fact that bivalves appear to possess several unique homologues to the initiator caspase groups − 2 and − 8. Large expansions of caspase-3 like homologues (caspase-3A-C), caspase-3/7 group and caspase-3/7-like homologues were also identified, suggesting unusual roles of caspases with direct implications for our understanding of immune response in relation to common bivalve diseases. Furthermore, we assessed the gene expression of two initiator (Cg2A, Cg8B) and four executioner caspases (Cg3A, Cg3B, Cg3C, Cg3/7) in C. gigas late-larval development and during metamorphosis, indicating that caspase expression varies across the different developmental stages. Conclusion Our analysis provides the first overview of caspases across different bivalve species with essential new insights into caspase diversity, knowledge that can be used for further investigations into immune response to pathogens or regulation of developmental processes.

scholarly journals Iron overload induced death of osteoblasts in vitro: involvement of the mitochondrial apoptotic pathway

PeerJ ◽  
2016 ◽  
Vol 4 ◽  
pp. e2611 ◽  
Author(s):  
Qing Tian ◽  
Shilei Wu ◽  
Zhipeng Dai ◽  
Jingjing Yang ◽  
Jin Zheng ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Iron Overload ◽  
Caspase 3 ◽  
Osteoblastic Cell ◽  
Ferric Ion ◽  
Oxygen Species ◽  
Mitochondrial Apoptosis ◽  
Apoptotic Pathway ◽  
Mitochondrial Apoptotic Pathway ◽  
Commercial Kits

BackgroundIron overload is recognized as a new pathogenfor osteoporosis. Various studies demonstrated that iron overload could induce apoptosis in osteoblasts and osteoporosis in vivo. However, the exact molecular mechanisms involved in the iron overload-mediated induction of apoptosis in osteoblasts has not been explored.PurposeIn this study, we attempted to determine whether the mitochondrial apoptotic pathway is involved in iron-induced osteoblastic cell death and to investigate the beneficial effect of N-acetyl-cysteine (NAC) in iron-induced cytotoxicity.MethodsThe MC3T3-E1 osteoblastic cell line was treated with various concentrations of ferric ion in the absence or presence of NAC, and intracellular iron, cell viability, reactive oxygen species, functionand morphology changes of mitochondria and mitochondrial apoptosis related key indicators were detected by commercial kits. In addition, to further explain potential mechanisms underlying iron overload-related osteoporosis, we also assessed cell viability, apoptosis, and osteogenic differentiation potential in bone marrow-derived mesenchymal stemcells(MSCs) by commercial kits.ResultsFerric ion demonstrated concentration-dependent cytotoxic effects on osteoblasts. After incubation with iron, an elevation of intracelluar labile iron levels and a concomitant over-generation of reactive oxygen species (ROS) were detected by flow cytometry in osteoblasts. Nox4 (NADPH oxidase 4), an important ROS producer, was also evaluated by western blot. Apoptosis, which was evaluated by Annexin V/propidium iodide staining, Hoechst 33258 staining, and the activation of caspase-3, was detected after exposure to iron. Iron contributed to the permeabilizatio of mitochondria, leading to the release of cytochrome C (cyto C), which, in turn, induced mitochondrial apoptosis in osteoblasts via activation of Caspase-3, up-regulation of Bax, and down-regulation of Bcl-2. NAC could reverse iron-mediated mitochondrial dysfunction and blocked the apoptotic events through inhibit the generation of ROS. In addition, iron could significantly promote apoptosis and suppress osteogenic differentiation and mineralization in bone marrow-derived MSCs.ConclusionsThese findings firstly demonstrate that the mitochondrial apoptotic pathway involved in iron-induced osteoblast apoptosis. NAC could relieved the oxidative stress and shielded osteoblasts from apoptosis casused by iron-overload. We also reveal that iron overload in bone marrow-derived MSCs results in increased apoptosis and the impairment of osteogenesis and mineralization.

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