scholarly journals Correction to: p63 regulates the caspase-8-FLIP apoptotic pathway in epidermis

2021 ◽  
Author(s):  
S. Borrelli ◽  
E. Candi ◽  
D. Alotto ◽  
C. Castagnoli ◽  
G. Melino ◽  
...  
Keyword(s):  
Caspase 8 ◽  
Apoptotic Pathway

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 Disease-Dependent Antiapoptotic Effects of Cannabidiol for Keratinocytes Observed upon UV Irradiation

2021 ◽  
Vol 22 (18) ◽  
pp. 9956
Author(s):  
Piotr Wójcik ◽  
Agnieszka Gęgotek ◽  
Neven Žarković ◽  
Elżbieta Skrzydlewska
Keyword(s):  
Signaling Pathways ◽  
Antioxidant Properties ◽  
Human Keratinocytes ◽  
Caspase 8 ◽  
Apoptotic Pathway ◽  
Healthy Human ◽  
Uvb Irradiation ◽  
Apoptotic Signaling ◽  
Anti Inflammatory

Although apoptosis of keratinocytes has been relatively well studied, there is a lack of information comparing potentially proapoptotic treatments for healthy and diseased skin cells. Psoriasis is a chronic autoimmune-mediated skin disease manifested by patches of hyperproliferative keratinocytes that do not undergo apoptosis. UVB phototherapy is commonly used to treat psoriasis, although this has undesirable side effects, and is often combined with anti-inflammatory compounds. The aim of this study was to analyze if cannabidiol (CBD), a phytocannabinoid that has anti-inflammatory and antioxidant properties, may modify the proapoptotic effects of UVB irradiation in vitro by influencing apoptotic signaling pathways in donor psoriatic and healthy human keratinocytes obtained from the skin of five volunteers in each group. While CBD alone did not have any major effects on keratinocytes, the UVB treatment activated the extrinsic apoptotic pathway, with enhanced caspase 8 expression in both healthy and psoriatic keratinocytes. However, endoplasmic reticulum (ER) stress, characterized by increased expression of caspase 2, was observed in psoriatic cells after UVB irradiation. Furthermore, decreased p-AKT expression combined with increased 15-d-PGJ2 level and p-p38 expression was observed in psoriatic keratinocytes, which may promote both apoptosis and necrosis. Application of CBD partially attenuated these effects of UVB irradiation both in healthy and psoriatic keratinocytes, reducing the levels of 15-d-PGJ2, p-p38 and caspase 8 while increasing Bcl2 expression. However, CBD increased p-AKT only in UVB-treated healthy cells. Therefore, the reduction of apoptotic signaling pathways by CBD, observed mainly in healthy keratinocytes, suggests the need for further research into the possible beneficial effects of CBD.

scholarly journals p38-mediated Regulation of an Fas-associated Death Domain Protein-independent Pathway Leading to Caspase-8 Activation during TGFβ-induced Apoptosis in Human Burkitt Lymphoma B Cells BL41

2001 ◽  
Vol 12 (10) ◽  
pp. 3139-3151 ◽  
Author(s):  
Nicolas Schrantz ◽  
Marie-Françoise Bourgeade ◽  
Shahul Mouhamad ◽  
Gérald Leca ◽  
Surendra Sharma ◽  
...  
Keyword(s):  
Membrane Potential ◽  
Mitochondrial Membrane Potential ◽  
Mitochondrial Membrane ◽  
Transforming Growth Factor ◽  
Dominant Negative ◽  
Dominant Negative Mutant ◽  
Caspase 8 ◽  
Death Domain ◽  
Apoptotic Pathway ◽  
Domain Protein

On binding to its receptor, transforming growth factor β (TGFβ) induces apoptosis in a variety of cells, including human B lymphocytes. We have previously reported that TGFβ-mediated apoptosis is caspase-dependent and associated with activation of caspase-3. We show here that caspase-8 inhibitors strongly decrease TGFβ-mediated apoptosis in BL41 Burkitt's lymphoma cells. These inhibitors act upstream of the mitochondria because they inhibited the loss of mitochondrial membrane potential observed in TGFβ-treated cells. TGFβ induced caspase-8 activation in these cells as shown by the cleavage of specific substrates, including Bid, and the appearance of cleaved fragments of caspase-8. Our data show that TGFβ induces an apoptotic pathway involving sequential caspase-8 activation, loss of mitochondrial membrane potential, and caspase-9 and -3 activation. Caspase-8 activation was Fas-associated death domain protein (FADD)-independent because cells expressing a dominant negative mutant of FADD were still sensitive to TGFβ-induced caspase-8 activation and apoptosis. This FADD-independent pathway of caspase-8 activation is regulated by p38. Indeed, TGFβ-induced activation of p38 and two different inhibitors specific for this mitogen-activated protein kinase pathway (SB203580 and PD169316) prevented TGFβ-mediated caspase-8 activation as well as the loss of mitochondrial membrane potential and apoptosis. Overall, our data show that p38 activation by TGFβ induced an apoptotic pathway via FADD-independent activation of caspase-8.

scholarly journals Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells

2010 ◽  
Vol 79 (9) ◽  
pp. 1261-1271 ◽  
Author(s):  
Cheng-Chih Hsieh ◽  
Yueh-Hsiung Kuo ◽  
Ching-Chuan Kuo ◽  
Li-Tzong Chen ◽  
Chun-Hei Antonio Cheung ◽  
...  
Keyword(s):  
Anticancer Activity ◽  
Cancer Cells ◽  
Human Cancer ◽  
Caspase 8 ◽  
Microtubule Inhibitor ◽  
Apoptotic Pathway ◽  
Human Cancer Cells

Carbon monoxide protects hepatocytes from TNF-α/Actinomycin D by inhibition of the caspase-8-mediated apoptotic pathway

2006 ◽  
Vol 344 (4) ◽  
pp. 1172-1178 ◽  
Author(s):  
Hoe Suk Kim ◽  
Patricia A. Loughran ◽  
Peter K. Kim ◽  
Timothy R. Billiar ◽  
Brian S. Zuckerbraun
Keyword(s):  
Carbon Monoxide ◽  
Actinomycin D ◽  
Caspase 8 ◽  
Apoptotic Pathway ◽  
Tnf Α

scholarly journals Vaccinia Virus Infection Disarms the Mitochondrion-Mediated Pathway of the Apoptotic Cascade by Modulating the Permeability Transition Pore

2001 ◽  
Vol 75 (23) ◽  
pp. 11437-11448 ◽  
Author(s):  
Shawn T. Wasilenko ◽  
Adrienne F. A. Meyers ◽  
Kathleen Vander Helm ◽  
Michele Barry
Keyword(s):  
Virus Infection ◽  
Vaccinia Virus ◽  
Permeability Transition Pore ◽  
Permeability Transition ◽  
Jurkat Cells ◽  
Caspase 8 ◽  
Apoptotic Pathway ◽  
Vaccinia Virus Infection ◽  
Infected Cells ◽  
Apoptotic Cascade

ABSTRACT Many viruses have evolved strategies that target crucial components within the apoptotic cascade. One of the best studied is the caspase 8 inhibitor, crmA/Spi-2, encoded by members of the poxvirus family. Since many proapoptotic stimuli induce apoptosis through a mitochondrion-dependent, caspase 8-independent pathway, we hypothesized that vaccinia virus would encode a mechanism to directly modulate the mitochondrial apoptotic pathway. In support of this, we observed that Jurkat cells, which undergo Fas-mediated apoptosis exclusively through the mitochondrial route, were resistant to Fas-induced death following infection with a crmA/Spi-2-deficient strain of vaccinia virus. In addition, vaccinia virus-infected cells subjected to the proapoptotic stimulus staurosporine exhibited decreased levels of both cytochromec released from the mitochondria and caspase 3 activation. In all cases we found that the loss of the mitochondrial membrane potential, which occurs as a result of opening the multimeric permeability transition pore complex, was prevented in vaccinia virus-infected cells. Moreover, vaccinia virus infection specifically inhibited opening of the permeability transition pore following treatment with the permeability transition pore ligand atractyloside and t-butylhydroperoxide. These studies indicate that vaccinia virus infection directly impacts the mitochondrial apoptotic cascade by influencing the permeability transition pore.

Decrease of Bcl-xL and augmentation of thymocyte apoptosis in GILZ overexpressing transgenic mice

Blood ◽  
2004 ◽  
Vol 104 (13) ◽  
pp. 4134-4141 ◽  
Author(s):  
Domenico Vittorio Delfino ◽  
Massimiliano Agostini ◽  
Stefania Spinicelli ◽  
Pasquale Vito ◽  
Carlo Riccardi
Keyword(s):  
Transgenic Mice ◽  
Time Course ◽  
Leucine Zipper ◽  
Caspase 3 ◽  
Ex Vivo ◽  
Cell Lineage ◽  
Caspase 8 ◽  
Apoptotic Pathway ◽  
Cell Counts ◽  
Thymocyte Apoptosis

Abstract Glucocorticoids promote thymocyte apoptosis and modulate transcription of numerous genes. GILZ (glucocorticoid-induced leucine zipper), being one of them, is strongly up-regulated in the thymus. To elucidate its function we generated transgenic mice overexpressing it specifically in the T-cell lineage and characterized its influence on thymus function. In young adult transgenic mice CD4+CD8+ thymocyte number was significantly decreased and ex vivo thymocyte apoptosis was increased. Apoptotic pathway analysis detected reduced antiapoptotic B-cell leukemia XL (Bcl-xL) expression and increased activation of caspase-8 and caspase-3. Time-course experiments showed that in wild-type (WT) thymocytes GILZ up-regulation was followed by sequential Bcl-xL decreased expression and activation of caspase-8 and of caspase-3. Moreover, GILZ delivered inside WT thymocytes by a fusion protein with the transactivator of transcription (TAT) peptide decreased Bcl-xL and promoted their apoptosis. In aged mice perturbation of thymic subset numbers was amplified over time, as demonstrated by a further decrease in CD4+CD8+ cells and increases in CD4+CD8-, CD4-CD8-, and CD8+CD4- cell counts. These results support the hypothesis that GILZ participates in the regulation of thymocyte apoptosis by glucocorticoids. (Blood. 2004;104:4134-4141)

scholarly journals Use of Fluorochrome-Labeled Inhibitors of Caspases to Detect Neuronal Apoptosis in the Whole-Mounted Lamprey Brain after Spinal Cord Injury

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
Antón Barreiro-Iglesias ◽  
Michael I. Shifman
Keyword(s):  
Spinal Cord ◽  
Neural Development ◽  
Neuronal Death ◽  
Neuronal Apoptosis ◽  
Caspase 8 ◽  
Caspase Inhibitor ◽  
Apoptotic Pathway ◽  
Cord Injury ◽  
Sea Lampreys ◽  
Apoptotic Neuronal Death

Apoptosis is a major feature in neural development and important in traumatic diseases. The presence of active caspases is a widely accepted marker of apoptosis. We report here the development of a method to study neuronal apoptotic death in whole-mounted brain preparations using fluorochrome-labeled inhibitors of caspases (FLICA). As a model we used axotomy-induced retrograde neuronal death in the CNS of larval sea lampreys. Once inside the cell, the FLICA reagents bind covalently to active caspases causing apoptotic cells to fluoresce, whereas nonapoptotic cells remain unstained. The fluorescent probe, the poly caspase inhibitor FAM-VAD-FMK, was applied to whole-mounted brain preparations of larval sea lampreys 2 weeks after a complete spinal cord (SC) transection. Specific labeling occurred only in identifiable spinal-projecting neurons of the brainstem previously shown to undergo apoptotic neuronal death at later times after SC transection. These neurons also exhibited intense labeling 2 weeks after a complete SC transection when a specific caspase-8 inhibitor (FAM-LETD-FMK) served as the probe. In this study we show that FLICA reagents can be used to detect specific activated caspases in identified neurons of the whole-mounted lamprey brain. Our results suggest that axotomy may cause neuronal apoptosis by activation of the extrinsic apoptotic pathway.

scholarly journals Caspase-8 inactivation in T cells increases necroptosis and suppresses autoimmunity in Bim−/− mice

2011 ◽  
Vol 195 (2) ◽  
pp. 277-291 ◽  
Author(s):  
Toshiyuki Bohgaki ◽  
Julien Mozo ◽  
Leonardo Salmena ◽  
Elzbieta Matysiak-Zablocki ◽  
Miyuki Bohgaki ◽  
...  
Keyword(s):  
T Cells ◽  
Death Receptor ◽  
Death Process ◽  
Caspase 8 ◽  
Intrinsic Apoptotic Pathway ◽  
Immune Disorders ◽  
Loss Of Function ◽  
T Cell Homeostasis ◽  
Apoptotic Pathway ◽  
Cell Death Process

Dysregulation of either the extrinsic or intrinsic apoptotic pathway can lead to various diseases including immune disorders and cancer. In addition to its role in the extrinsic apoptotic pathway, caspase-8 plays nonapoptotic functions and is essential for T cell homeostasis. The pro-apoptotic BH3-only Bcl-2 family member Bim is important for the intrinsic apoptotic pathway and its inactivation leads to autoimmunity that is further exacerbated by loss of function of the death receptor Fas. We report that inactivation of caspase-8 in T cells of Bim−/− mice restrained their autoimmunity and extended their life span. We show that, similar to caspase-8−/− T cells, Bim−/− T cells that also lack caspase-8 displayed elevated levels of necroptosis and that inhibition of this cell death process fully rescued the survival and proliferation of these cells. Collectively, our data demonstrate that inactivation of caspase-8 suppresses the survival and proliferative capacity of Bim−/− T cells and restrains autoimmunity in Bim−/− mice.

scholarly journals Evidence for a Novel, Caspase-8-Independent, Fas Death Domain-Mediated Apoptotic Pathway

2004 ◽  
Vol 2004 (1) ◽  
pp. 41-51 ◽  
Author(s):  
Hanping Feng ◽  
Yi Zeng ◽  
Michael W. Graner ◽  
Luke Whitesell ◽  
Emmanuel Katsanis
Keyword(s):  
Transmembrane Potential ◽  
Caspase 8 ◽  
Death Domain ◽  
Caspase Inhibitor ◽  
Caspase Activation ◽  
Null Cell ◽  
Apoptotic Pathway ◽  
Induced Apoptosis ◽  
Mitochondrial Transition Pore ◽  
Pore Permeability

Certain caspase-8 null cell lines demonstrate resistance to Fas-induced apoptosis, indicating that the Fas/FasL apoptotic pathway may be caspase-8-dependent. Some reports, however, have shown that Fas induces cell death independent of caspase-8. Here we provide evidence for an alternative, caspase-8-independent, Fas death domain-mediated apoptotic pathway. Murine 12B1-D1 cells express procaspase-3, -8, and -9, which were activated upon the dimerization of Fas death domain. Bid was cleaved and mitochondrial transmembrane potential was disrupted in this apoptotic process. All apoptotic events were completely blocked by the broad-spectrum caspase inhibitor Z-VAD-FMK, but not by other peptide caspase inhibitors. Cyclosporin A (CsA), which inhibits mitochondrial transition pore permeability, blocked neither pore permeability disruption nor caspase activation. However, CsA plus caspase-8 inhibitor blocked all apoptotic events of 12B1-D1 induced by Fas death domain dimerization. Our data therefore suggest that there is a novel, caspase-8-independent, Z-VAD-FMK-inhibitable, apoptotic pathway in 12B1-D1 cells that targets mitochondria directly.

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