scholarly journals Caspase-8 and Apaf-1-independent Caspase-9 Activation in Sendai Virus-infected Cells

2002 ◽  
Vol 277 (33) ◽  
pp. 29817-29824 ◽  
Author(s):  
Michael Bitzer ◽  
Sorin Armeanu ◽  
Florian Prinz ◽  
Guy Ungerechts ◽  
Wolfgang Wybranietz ◽  
...  
Keyword(s):  
Sendai Virus ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Infected Cells

scholarly journals Role of the Mitochondrial Signaling Pathway in Murine Coronavirus-Induced Oligodendrocyte Apoptosis

2006 ◽  
Vol 80 (1) ◽  
pp. 395-403 ◽  
Author(s):  
Yin Liu ◽  
Yinghui Pu ◽  
Xuming Zhang
Keyword(s):  
Hepatitis Virus ◽  
Mitochondrial Pathway ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Apoptotic Pathway ◽  
Antiapoptotic Proteins ◽  
Mitochondrial Signaling ◽  
Drastic Increase ◽  
Infected Cells

ABSTRACT A previous study demonstrated that infection of rat oligodendrocytes by mouse hepatitis virus (MHV) resulted in apoptosis, which is caspase dependent (Y. Liu, Y. Cai, and X. Zhang, J. Virol. 77:11952-11963, 2003). Here we determined the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis. We found that caspase-9 activity was 12-fold higher in virus-infected cells than in mock-infected cells at 24 h postinfection (p.i.). Pretreatment of cells with a caspase-9 inhibitor completely blocked caspase-9 activation and partially inhibited the apoptosis mediated by MHV infection. Analyses of cytochrome c release further revealed an activation of the mitochondrial apoptotic pathway. Stable overexpression of the two antiapoptotic proteins Bcl-2 and Bcl-xL significantly, though only partially, blocked apoptosis, suggesting that activation of the mitochondrial pathway is partially responsible for the apoptosis. To identify upstream signals, we determined caspase-8 activity, cleavage of Bid, and expression of Bax and Bad by Western blotting. We found a drastic increase in caspase-8 activity and cleavage of Bid at 24 h p.i. in virus-infected cells, suggesting that Bid may serve as a messenger to relay the signals from caspase-8 to mitochondria. However, treatment with a caspase-8 inhibitor only slightly blocked cytochrome c release from the mitochondria. Furthermore, we found that Bax but not Bad was significantly increased at 12 h p.i. in cells infected with both live and UV-inactivated viruses and that Bax activation was partially blocked by treatment with the caspase-8 inhibitor. These results thus establish the involvement of the mitochondrial pathway in MHV-induced oligodendrocyte apoptosis.

scholarly journals Sendai Virus Infection Induces Apoptosis through Activation of Caspase-8 (FLICE) and Caspase-3 (CPP32)

1999 ◽  
Vol 73 (1) ◽  
pp. 702-708 ◽  
Author(s):  
Michael Bitzer ◽  
Florian Prinz ◽  
Manuel Bauer ◽  
Martin Spiegel ◽  
Wolfgang J. Neubert ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Cell Injury ◽  
Sendai Virus ◽  
Host Cells ◽  
Target Cells ◽  
Caspase 8 ◽  
Proteolytic Activation ◽  
Caspase Family ◽  
Infected Cells ◽  
Induced Apoptosis

ABSTRACT Sendai virus (SV) infection and replication lead to a strong cytopathic effect with subsequent death of host cells. We now show that SV infection triggers an apoptotic program in target cells. Incubation of infected cells with the peptide inhibitor z-VAD-fmk abrogated SV-induced apoptosis, indicating that proteases of the caspase family were involved. Moreover, proteolytic activation of two distinct caspases, CPP32/caspase-3 and, as shown for the first time in virus-infected cells, FLICE/caspase-8, could be detected. So far, activation of FLICE/caspase-8 has been described in apoptosis triggered by death receptors, including CD95 and tumor necrosis factor (TNF)-R1. In contrast, we could show that SV-induced apoptosis did not require TNF or CD95 ligand. We further found that apoptosis of infected cells did not influence the maturation and budding of SV progeny. In conclusion, SV-induced cell injury is mediated by CD95- and TNF-R1-independent activation of caspases, leading to the death of host cells without impairment of the viral life cycle.

scholarly journals Inclusion Complex of Zerumbone with Hydroxypropyl-β-Cyclodextrin Induces Apoptosis in Liver Hepatocellular HepG2 Cells via Caspase 8/BID Cleavage Switch and Modulating Bcl2/Bax Ratio

2013 ◽  
Vol 2013 ◽  
pp. 1-16 ◽  
Author(s):  
Nabilah Muhammad Nadzri ◽  
Ahmad Bustamam Abdul ◽  
Mohd Aspollah Sukari ◽  
Siddig Ibrahim Abdelwahab ◽  
Eltayeb E. M. Eid ◽  
...  
Keyword(s):  
Inclusion Complex ◽  
Mitochondrial Membrane ◽  
Morphological Study ◽  
Caspase 3 ◽  
Anticancer Agent ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Solubility In Water ◽  
Anticancer Effects ◽  
First Time

Zerumbone (ZER) isolated fromZingiber zerumbetwas previously encapsulated with hydroxypropyl-β-cyclodextrin (HPβCD) to enhance ZER’s solubility in water, thus making it highly tolerable in the human body. The anticancer effects of this new ZER-HPβCD inclusion complex via apoptosis cell death were assessed in this study for the first time in liver hepatocellular cells, HepG2. Apoptosis was ascertained by morphological study, nuclear stain, and sub-G1 cell population accumulation with G2/M arrest. Further investigations showed the release of cytochrome c and loss of mitochondrial membrane potential, proving mitochondrial dysfunction upon the ZER-HPβCD treatment as well as modulating proapoptotic and anti-apototic Bcl-2 family members. A significant increase in caspase 3/7, caspase 9, and caspase 8 was detected with the depletion of BID cleaved by caspase 8. Collectively, these results prove that a highly soluble inclusion complex of ZER-HPβCD could be a promising anticancer agent for the treatment of hepatocellular carcinoma in humans.

Sendai virus replication in Friend erythroleukemia cells. I. Acutely and persistently infected cells become resistant to virus-induced lysis

1986 ◽  
Vol 4 (2) ◽  
pp. 117-132
Author(s):  
Arrigo Benedetto ◽  
Carla Amici ◽  
Stefania Zaniratti ◽  
Giuliano Elia ◽  
Maria Pia Camporiondo
Keyword(s):  
Virus Replication ◽  
Sendai Virus ◽  
Persistently Infected ◽  
Erythroleukemia Cells ◽  
Infected Cells ◽  
Friend Erythroleukemia Cells

scholarly journals Protective Effects of Shenfuyixin Granule on H2O2-Induced Apoptosis in Neonatal Rat Cardiomyocytes

2021 ◽  
Vol 2021 ◽  
pp. 1-10
Author(s):  
Xinlu Wang ◽  
Xuanxuan Hao ◽  
Youping Wang ◽  
Bin Li ◽  
Lin Cui ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Caspase 3 ◽  
Neonatal Rat ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Rat Cardiomyocytes ◽  
Expression Levels ◽  
Apoptosis Rate ◽  
Neonatal Rat Cardiomyocytes ◽  
Mitochondrion Membrane Potential

Shenfuyixin granule (SFYXG, i.e., Xinshuaikang granule) is a prescription, commonly used in the clinical experience, which plays a significant role in the treatment of heart failure. The purpose of this present research was to investigate the protective effect of SFYXG, and the mechanism about anti-H2O2-induced oxidative stress and apoptosis in the neonatal rat cardiomyocytes. Myocardial cells, as is well known, were divided into 4 groups: normal, model, SFYXG, and coenzyme Q10 group, respectively. Cells viability was determined by MTT assay. Flow cytometry and AO/EB staining were implemented to test the apoptosis rate and intracellular reactive oxygen species (ROS) level. Mitochondrion membrane potential (MMP) was evaluated by JC-1 fluorescence probe method. The myocardial ultrastructure of mitochondrion was measured by electron microscope. The related mRNA expression levels of Bax, Bcl-2, Caspase-3, caspase-8, and caspase-9 were detected by real-time polymerase chain reaction (PCR). Also, the expression levels of Bax and Bcl-2 protein were detected by Western blot, and the expression levels of caspase-3, caspase-8, and caspase-9 protein were tested by caspase-Glo®3 Assay, caspase-Glo®8 Assay, and caspase-Glo®9 Assay, respectively. GAPDH was used as the internal reference gene/protein. The results revealed that SFYXG (0.5 mg/ml) raised the viability of myocardial cell, weakened the apoptosis rate and ROS level, corrected the mitochondrion membrane potential stability, and improved cell morphology and ultrastructure of myocardial mitochondrion. Furthermore, SFYXG upregulated the antiapoptosis gene of Bcl-2, but downregulated the proapoptosis genes of Bax, caspase-3, and caspase-9. In conclusion, SFYXG could appear to attenuate myocardial injury by its antioxidative and antiapoptosis effect.

scholarly journals Antiproliferative and Apoptotic Effects of Red Beetroot and Betanin on Human Colorectal Cancer Cell Lines

2021 ◽  
Author(s):  
Amir Saber ◽  
Nasim Abedimanesh ◽  
Mohammad-Hossein Somi ◽  
Ahmad Yari Khosroushahi
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Caspase 3 ◽  
Caspase 8 ◽  
Alcoholic Extract ◽  
Caspase 9 ◽  
Dapi Staining ◽  
Normal Cells ◽  
Colorectal Cancer Cell Lines ◽  
Ht 29

Abstract Background: Colorectal cancer (CRC) is the third most common type of cancer worldwide. Fruit and vegetables have some active compounds such as flavonoids and polyphenols that protect against malignancies through their antioxidative, anti-inflammatory, anti-proliferative, neuro, and hepatoprotective properties. Red beetroot (Beta vulgaris) contains red (betacyanins) and yellow (betaxanthins) pigments known as betalains. Betanin makes up 75-95% of the total betacyanins, possessed a wide range of favorable biological effects such as chemopreventive, anticarcinogenic, anti-tumorogenic, antiangiogenic, and proapoptotic effects. Methods: Red beetroot hydro-alcoholic extract and betanin were used to treat Caco-2 and HT-29 colorectal cancer cells, as well as KDR/293 normal epithelial cells. The half-maximal inhibitory concentration (IC50) was determined by prescreening MTT tests in the range of 20 to 140 µg/ml at 24 and 48 h. The cytotoxicity and apoptosis-inducing evaluations were performed via MTT assay, DAPI staining, and FACS-flow cytometry tests using determined times and doses. Moreover, the expression level of six important genes involving in the apoptosis pathway (Bcl-2, BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) were determined using the real-time polymerase chain reaction (RT-PCR) method.Results: The IC50 doses for HT-29 and Caco-2 cell lines were determined to be about 92 μg/mL, 107 μg/mL for beetroot hydro-alcoholic extract, and 64 μg/mL, 90 μg/mL for betanin at 48 h, respectively. Our findings showed that beetroot extract and betanin significantly inhibit the growth of HT-29 and Caco-2 cell lines, time and dose-dependently, without considerable adverse effects on KDR/293 normal cells. Moreover, DAPI staining and flow cytometry results revealed significant apoptosis symptoms in treated cancerous cell lines. The expression level of pro-apoptotic genes involved in intrinsic and extrinsic apoptosis pathways (BAD, Caspase-3, Caspase-8, Caspase-9, and Fas-R) in treated HT-29 and Caco-2 cells was higher than untreated and normal cells, whereas the anti-apoptotic gene (Bcl-2) was downregulated. Conclusion: Beetroot hydro-alcoholic extract and betanin significantly inhibited cell proliferation and induced cell apoptosis (intrinsic and extrinsic pathways) via modification of effective genes in both colorectal cancer cell lines with no significant cytotoxic effects on KDR/293 normal cells. The mechanism of the anticancer effects of red beetroot extract and betanin needs to be further studied.

RGDS peptide induces caspase 8 and caspase 9 activation in human endothelial cells

Blood ◽  
2004 ◽  
Vol 103 (11) ◽  
pp. 4180-4187 ◽  
Author(s):  
Maria Simona Aguzzi ◽  
Claudia Giampietri ◽  
Francesco De Marchis ◽  
Fabrizio Padula ◽  
Roberto Gaeta ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Umbilical Vein ◽  
Caspase 8 ◽  
Caspase 9 ◽  
Experimental Conditions ◽  
Biologic Effects ◽  
Independent Effects ◽  
Hoechst Staining ◽  
Umbilical Vein Endothelial Cells

Abstract Peptides containing the Arg-Gly-Asp (RGD) motif inhibit cell adhesion and exhibit a variety of other biologic effects including anticoagulant and antimetastatic activities. The aim of the present study was to examine the anchorage-independent effects of an RGD-containing peptide, Arg-Gly-Asp-Ser (RGDS), on human umbilical vein endothelial cells (HUVECs). Assays were performed on HUVECs seeded onto collagen IV; under these experimental conditions RGDS did not exert antiadhesive effects but significantly reduced FGF-2-dependent chemotaxis after 4 hours of treatment and reduced proliferation after 24 hours of treatment. Experiments carried out with caspase-specific inhibitors indicated that the observed antichemotactic effects required caspase 8 and caspase 9 activation. RGDS activated both caspase 8 and caspase 9 after 4 hours of treatment and caspase 3 after 24 hours of treatment, and markedly enhanced HUVEC apoptosis by transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL)/Hoechst staining and fluorescence-activated cell sorting (FACS) analysis. Finally, confocal microscopy showed that RGDS localizes in the cytoplasm of live HUVECs within 4 hours and in vitro experiments showed that RGDS directly interacts with recombinant caspases 8 and 9 in a specific way. In summary, these results indicate that RGDS directly binds and activates caspases 8 and 9, inhibits chemotaxis, and induces apoptosis of HUVECs with a mechanism independent from its antiadhesive effect.

scholarly journals Heat shock and tumor necrosis factor-α induce apoptosis in bovine preimplantation embryos through a caspase-9-dependent mechanism

Reproduction ◽  
2007 ◽  
Vol 133 (6) ◽  
pp. 1129-1137 ◽  
Author(s):  
Bárbara Loureiro ◽  
Amber Mary Brad ◽  
Peter James Hansen
Keyword(s):  
Heat Shock ◽  
Tumor Necrosis ◽  
Preimplantation Embryos ◽  
Caspase 8 ◽  
Mitochondrial Depolarization ◽  
Caspase 9 ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor ◽  
Dependent Mechanism

Heat shock and tumor necrosis factor-α (TNF-α) induce apoptosis through different mechanisms, with heat shock acting to cause mitochondrial depolarization and caspase-9 activation, while TNF-α acts through a receptor-mediated process to activate caspase-8. In some cells, however, TNF-α can also cause mitochondrial depolarization and caspase-9 activation. In the present study, we tested the hypothesis that heat shock at 41 °C and TNF-α induce apoptosis in bovine preimplantation embryos through a caspase-9-dependent mechanism. Treatment of embryos with either heat shock (41 °C) or TNF-α increased the proportion of blastomeres that were TUNEL positive and the proportion of embryos exhibiting elevated caspase-9 activity. Furthermore, the caspase-9 inhibitor, z-LEHD-fmk, blocked the increase in TUNEL-positive nuclei caused by both heat shock and TNF-α. For embryos at day 6 after insemination, for example, the percent of blastomeres positive for TUNEL was 3.6% for control embryos, 11.1% for embryos cultured at 41 °C, and 15.1% for embryos cultured with 10 ng/ml TNF-α. In the presence of z-LEHD-fmk, the percent of cells positive for TUNEL was 3.7% for control embryos, 6.1% for embryos cultured at 41 °C, and 8% for embryos cultured with 10 ng/ml TNF-α. Although TNF-α did not cause a measurable increase in caspase-8 activity, there was a tendency (P= 0.07) for treatment of embryos with z-IETD-fmk, an inhibitor of caspase-8, to partly reduce the magnitude of the increase in TUNEL-positive cells caused by TNF-α. The percent of cells that were TUNEL positive was increased by TNF-α from 9.7 to 19.7% in the absence of inhibitor and from 13.0 to 15.6% in the presence of z-IETD-fmk. Results indicate that induction of apoptosis by both heat shock and TNF-α involve activation of caspase-9-dependent pathways. It is likely that TNF-α also activates apoptotic pathways involving caspase-8 but that the degree of activation is small and caspase-9-dependent pathways are required for full activation of apoptosis.

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