Fas Activation Research Articles

Differential effects of alpha-particle radiation and x-irradiation on genes associated with apoptosis.

This study examined differential effects of alpha-(α-) particle radiation and X-rays on apoptosis and associated changes in gene expression. Human monocytic cells were exposed to α-particle radiation and X-rays from 0 to 1.5 Gy. Four days postexposure, cell death was measured by flow cytometry and 84 genes related to apoptosis were analyzed using real-time PCR. On average, 33% of the cells were apoptotic at 1.5 Gy of α-particle radiation. Transcript profiling showed statistical expression of 15 genes at all three doses tested. Cells exposed to X-rays were <5% apoptotic at ~1.5 Gy and induced less than a 2-fold expression in 6 apoptotic genes at the higher doses of radiation. Among these 6 genes, Fas and TNF-α were common to the α-irradiated cells. This data suggests that α-particle radiation initiates cell death by TNF-α and Fas activation and through intermediate signalling mediators that are distinct from X-irradiated cells.

The Adaptor Protein TRIP6 Antagonizes Fas-Induced Apoptosis but Promotes Its Effect on Cell Migration

The Fas/CD95 receptor mediates apoptosis but is also capable of triggering nonapoptotic signals. However, the mechanisms that selectively regulate these opposing effects are not yet fully understood. Here we demonstrate that the activation of Fas or stimulation with lysophosphatidic acid (LPA) induces cytoskeletal reorganization, leading to the association of Fas with actin stress fibers and the adaptor protein TRIP6. TRIP6 binds to the cytoplasmic juxtamembrane domain of Fas and interferes with the recruitment of FADD to Fas. Furthermore, through physical interactions with NF-κB p65, TRIP6 regulates nuclear translocation and the activation of NF-κB upon Fas activation or LPA stimulation. As a result, TRIP6 antagonizes Fas-induced apoptosis and further enhances the antiapoptotic effect of LPA in cells that express high levels of TRIP6. On the other hand, TRIP6 promotes Fas-mediated cell migration in apoptosis-resistant glioma cells. This effect is regulated via the Src-dependent phosphorylation of TRIP6 at Tyr-55. As TRIP6 is overexpressed in glioblastomas, this may have a significant impact on enhanced NF-κB activity, resistance to apoptosis, and Fas-mediated cell invasion in glioblastomas.

Gonadal steroids modulate Fas-induced apoptosis of lactotropes and somatotropes

We have previously reported that Fas activation induces apoptosis of anterior pituitary cells from rats at proestrus but not at diestrus and in an estrogen-dependent manner. In this study, we evaluated the effect of Fas activation on apoptosis of lactotropes and somatotropes during the estrous cycle and explored the action of gonadal steroids on Fas-induced apoptosis. Also, we studied whether changes in Fas expression are involved in the apoptotic response of anterior pituitary cells. Fas activation increased the percentage of TUNEL-positive lactotropes and somatotropes at proestrus but not at diestrus. FasL triggered apoptosis of somatotropes only when cells from ovariectomized rats were cultured in the presence of 17 β-estradiol (E2). Progesterone (P4) blocked the apoptotic action of the Fas/FasL system in lactotropes and somatotropes incubated with E2. Both E2 and P4 increased the percentage of cells expressing Fas at the cell membrane. Our results show that Fas activation induces apoptosis of lactotropes and somatotropes at proestrus but not at diestrus. Gonadal steroids may be involved in the apoptotic response of lactotropes and somatotropes, suggesting that Fas activation is implicated in the renewal of these pituitary subpopulations during the estrous cycle. The effect of gonadal steroids on Fas expression may be only partially involved in regulation of the Fas/FasL apoptotic pathway in the anterior pituitary gland.

Fas activation in adipocytes impairs insulin-stimulated glucose uptake by reducing Akt

Fas (CD95) belongs to the superfamily of the tumor necrosis factor (TNF) receptors. Besides its key role in apoptosis, Fas contributes to non-apoptotic pathways such as cell proliferation and inflammation. In 3T3-L1 adipocytes, activation of Fas by Fas ligand decreased insulin-stimulated glucose uptake, without affecting cell viability. This decrease in glucose uptake was accompanied by reduced protein expression and diminished phosphorylation of Akt. Similarly, insulin-stimulated glucose incorporation and protein levels of Akt were increased in isolated adipocytes from Fas deficient mice when compared to wild-type mice. In conclusion, Fas activation in adipocytes decreases Akt expression and thereby impairs insulin sensitivity.

Insulin signaling in fatty acid and fat synthesis: a transcriptional perspective

Transcription of enzymes involved in FA and TAG synthesis is coordinately induced in lipogenic tissues by feeding and insulin treatment. The three major transcription factors involved are USF, SREBP-1c, and LXRα. New insights into the insulin-signaling pathway(s) that control(s) lipogenic gene transcription via these factors have recently been revealed. Dephosphorylation/activation of DNA-PK by PP1 causes phosphorylation of USF that in turn recruits P/CAF to be acetylated for transcriptional activation. SREBP-1c can be induced by mTORC1, bifurcating lipogenesis from AKT-activated gluconeogenesis. LXRα may serve as a glucose sensor and, along with ChREBP, may activate lipogenic genes in the fed state. Dysregulation of FA and TAG metabolism often contributes to metabolic diseases such as obesity, diabetes, and cardiovascular diseases. Transcription factors and signaling molecules involved in transcriptional activation of FA and TAG synthesis represent attractive targets for the prevention and treatment of metabolic diseases.

HO-3867, a Synthetic Compound, Inhibits the Migration and Invasion of Ovarian Carcinoma Cells through Downregulation of Fatty Acid Synthase and Focal Adhesion Kinase

Fatty acid synthase (FAS) and focal adhesion kinase (FAK), which are overexpressed in a variety of human epithelial tumors, play a key role in the migration and invasion of cancer cells. Hence, strategies targeted at inhibiting the FAS/FAK proteins may have therapeutic potential for cancer treatment. The goal of the present study was to determine the effect of HO-3867, a synthetic compound, on the migratory ability of ovarian cancer cells and to understand the mechanistic pathways including the involvement of FAS, FAK, and associated signaling proteins. The study was done using two established human ovarian cancer cell lines, A2780 and SKOV3. Incubation with 10 μmol/L HO-3867 for 24 hours significantly inhibited the native as well as the vascular endothelial growth factor (VEGF)-mediated migration and invasion of the cells. HO-3867 significantly attenuated FAS and FAK protein levels apparently through accelerated ubiquitin-dependent degradation, as shown by a clear downregulation of isopeptidase USP2a. Exposure of cells to HO-3867 also significantly inhibited FAS activity and mRNA levels and a number of downstream proteins, including phospho-extracellular signal-regulated kinase 1/2, phospho-human epidermal growth factor receptor 1, sterol regulatory element binding protein 1, VEGF, and matrix metalloproteinase 2. Western blot and immunohistochemical analyses of A2780 xenograft tumors in mice treated with HO-3867 showed significant reduction in FAS, FAK, VEGF, and downstream protein levels when compared with the untreated control. Collectively, the results showed that HO-3867 suppressed the migration and invasion of ovarian cancer cells by inhibiting the expression or activity of FAS and FAK proteins. The study suggests that molecular targeting of FAS and FAK by HO-3867 may be a potential strategy for ovarian cancer therapy.

NFAT/Fas signaling mediates the neuronal apoptosis and motor side effects of GSK-3 inhibition in a mouse model of lithium therapy

Use of lithium, the mainstay for treatment of bipolar disorder, is limited by its frequent neurological side effects and its risk for overdose-induced toxicity. Recently, lithium has also been proposed as a treatment for Alzheimer disease and other neurodegenerative conditions, but clinical trials have been hampered by its prominent side effects in the elderly. The mechanisms underlying both the positive and negative effects of lithium are not fully known. Lithium inhibits glycogen synthase kinase-3 (GSK-3) in vivo, and we recently reported neuronal apoptosis and motor deficits in dominant-negative GSK-3-transgenic mice. We hypothesized that therapeutic levels of lithium could also induce neuronal loss through GSK-3 inhibition. Here we report induction of neuronal apoptosis in various brain regions and the presence of motor deficits in mice treated chronically with lithium. We found that GSK-3 inhibition increased translocation of nuclear factor of activated T cells c3/4 (NFATc3/4) transcription factors to the nucleus, leading to increased Fas ligand (FasL) levels and Fas activation. Lithium-induced apoptosis and motor deficits were absent when NFAT nuclear translocation was prevented by cyclosporin A administration and in Fas-deficient lpr mice. The results of these studies suggest a mechanism for lithium-induced neuronal and motor toxicity. These findings may enable the development of combined therapies that diminish the toxicities of lithium and possibly other GSK-3 inhibitors and extend their potential to the treatment of Alzheimer disease and other neurodegenerative conditions.

Resistance of neonatal primary astrocytes against Fas-induced apoptosis depends on silencing of caspase 8

In the present report, we have found that primary fetal astrocytes express caspase 8 and undergo apoptosis in response to Fas ligation. In contrast, neonatal astrocytes do not express detectable levels of the enzyme and are resistant to Fas killing. Fas-induced apoptosis can be restored in these cells by up-regulation of caspase 8 expression by means of transient transfection with a caspase 8-encoding plasmid. Furthermore, treatment of primary astrocytes with the demethylating agent 5-Aza-dC restores caspase 8 expression and increases the sensibility of neonatal astrocytes to the cytotoxic effect of Fas activation. Altogether, our findings indicate that silencing of caspase 8 gene is a key factor controlling the outcome of neonatal astrocytes upon Fas engagement.

Modulation of blackspot seabream (Pagellus bogaraveo) intermediary metabolic pathways by dispensable amino acids

The objective of the present work is to investigate the main metabolic pathways by which dispensable amino acids (DAA) are diverted towards lipid formation in blackspot seabream. For that purpose, a control diet was formulated to contain 45% of crude protein (7.2gN/100g dry matter) mainly supplied by fish meal (45P). In two other diets, 22.2% of the dietary nitrogen (1.6gN/100g dry matter) was replaced by an equivalent amount of nitrogen provided by two different mixtures of DAA: alanine and serine (diet AS) or aspartic and glutamic acid (diet AG). A fourth diet (diet 35P) only containing 35% of crude protein (5.6gN/100g dry matter) was included in order to analyze the possible additive effects of DAA. Compared to fish fed diet 35P, blackspot seabream appear to make a more efficient use of the nitrogen provided by alanine and serine than that provided by aspartic and glutamic acids in terms of growth. Contrary to fish fed AG, fish fed AS attained similar specific FAS activities as 45P fed fish, suggesting a further role of alanine and serine on this lipogenic pathway. Dietary nitrogen reduction (45P vs. 35P) or its replacement by a mixture of aspartic and glutamic acids (diet AG) were shown to up-regulate phosphoenolpyruvate carboxykinase (PEPCK) but without, however, any effect on plasma glucose levels. Dietary nitrogen level and nature seems to exert a complex regulation on energetic pathways through the gluconeogenesis/tricarboxylic acids cycle interaction.

Ouabain-induced perturbations in intracellular ionic homeostasis regulate death receptor-mediated apoptosis

Apoptosis is defined by specific morphological and biochemical characteristics including cell shrinkage (termed apoptotic volume decrease), a process that results from the regulation of ion channels and plasma membrane transporter activity. The Na(+)-K(+)-ATPase is the predominant pump that controls cell volume and plasma membrane potential in cells and alterations in its function have been suggested to be associated with apoptosis. We report here that the Na(+)-K(+)-ATPase inhibitor ouabain, potentiates apoptosis in the human lymphoma Jurkat cells exposed to Fas ligand (FasL) or tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) but not other apoptotic agents such as H(2)O(2), thapsigargin or UV-C implicating a role for the Na(+)-K(+)-ATPase in death receptor-induced apoptosis. Interestingly, ouabain also potentiated perturbations in cell Ca(2+) homeostasis only in conjunction with the apoptotic inducer FasL but not TRAIL. Ouabain did not affect alterations in the intracellular Ca(2+) levels in response to H(2)O(2), thapsigargin or UV-C. FasL-induced alterations in Ca(2+) were not abolished in Ca(2+)-free medium but incubation of cells with BAPTA-AM inhibited both Ca(2+) perturbations and the ouabain-induced potentiation of FasL-induced apoptosis. Our data suggest that the impairment of the Na(+)-K(+)-ATPase activity during apoptosis is linked to perturbations in cell Ca(2+) homeostasis that modulate apoptosis induced by the activation of Fas by FasL.

Abstract 5289: HO-3867 inhibits cell migration, invasion and tumor growth of ovarian cancer through alterations in fatty acid synthase (FASN) and focal adhesion kinase (FAK) signaling

Abstract Fatty acid synthase (FAS) has been found to be overexpressed in a wide range of epithelial tumors, including ovarian cancer. Expression of FAS, the key enzyme in de novo synthesis of long-chain fatty acids, is normally low but increases in cancer. The increase of FAS levels regulates cell proliferation, apoptosis and migration in tumors. In tumor cells, the inhibition of FAS elicits cell cycle arrest and apoptosis, so it is considered a potential drug target for cancer therapy. A2780 and SKOV3 ovarian cancer cells were grown in vitro and exposed to culture media containing 10 μM of HO-3867 for a period of 12 or 24 hours. FAS protein level analysis and examination of proliferation and migration genes was performed by Western blotting. RT-PCR was used to examine mRNA levels. FAS activity levels were measured by spectrophotometry. FAS, Cyclin D1 and VEGF expression levels were analyzed in vivo using both Western blotting, RT-PCR and immunohistochemistry. We found that HO-3867 significantly inhibits the FAS activity levels in A2780 and SKOV3 ovarian cancer cells. FAS mRNA levels were significantly decreased in HO-3867-treated cells. Based upon these results, we investigated how HO-3867 inhibits FAS expression and activity in ovarian cancer cells. We found that FAS-regulating genes such as SREBP1 &amp; 2 and pHER1 were clearly inhibited by HO-3867 exposure. Collectively, our results indicate that HO-3867 inhibition of FAS leads to inhibition of the cell migration genes FAK, ERK1/2, c-Myc, upregulation of the proliferation-regulating genes p21, p27 and downregulation of cyclin D1, resulting in inhibition of ovarian cancer cell proliferation, migration and tumor growth. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5289.

Abstract 4441: Stichoposides induce apoptosis through the generation of ceramide in human leukemia cells

Abstract Marine triterpene glycosides are physiologically active natural compounds, isolated from sea cucumbers (holothurians) and demonstrate a wide spectrum of biological effects. Stichoposides are extracted from Thelenota anax (family Stichopodidae). Previous studies demonstrated that stichoposides had antifungal, cytotoxic, and antitumor activities. However, the specific molecular mechanisms underlying this effect remain to be elucidated. Stichoposide-induced apoptosis was examined in human leukemia cells in relation to mitochondrial injury and perturbations in signaling pathways. Stichoposide C (STC) induces apoptosis in these cells in a dose-dependent manner and leads to the activation of FAS, recruitment of FADD, activation of caspase-8, cleavage of Bid, mitochondrial damage and activation of caspase-3. In contrast, stichoposide D (STD) induces apoptosis in these cells in a dose-dependent manner and causes to activation of extrinsic pathway, not to activation of intrinsic pathway. In addition, STC- and STD-induced apoptosis are mediated by ER stress pathway, showing that Salubrinal, ER pathway inhibitor, inhibits apoptosis by STC and STD. STD activated acid sphingomyelinase (SMase) and neutral SMase, resulting in the generation of ceramide, but STC slightly activated them. By using specific inhibitor for acid SMase or neutral SMase and siRNA knockdown experiments, stichoposides-induced apoptosis was blocked. Thus, these results indicate that ceramide generation by stichoposides may contribute to stichoposides-induced apoptosis. Thus, these data suggest that stichoposides may have therapeutic relevance in the treatment of human leukemia. This study was supported by the Korea Science and Engineering Foundation (KOSEF) grant funded by the Korea government (MEST) through the Medical Research Center for Cancer Molecular Therapy at Dong-A University (R13-2002-044-05002-0). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4441.

Abstract 5457: High levels of fatty acid synthase expression in esophageal cancers represent a potential target for therapy

Abstract Fatty acid synthase (FAS) is overexpressed in many human cancers and is considered to be a promising target for therapy. To investigate the expression of this candidate target in esophageal cancer, we evaluated expression of FAS protein in - cases of esophageal squamous cancer, - cases of esophageal adenocarcinoma, and - cases of Barrett's esophagus with dysplasia - a lesion thought to represent a pre-invasive precursor to esophageal cancer. Using immunohistochemistry, we found significantly higher levels of FAS expression in -% of the squamous cancers and -% of the adenocarcinomas compared to normal esophageal epithelium. To evaluate the potential for inhibiting this enzyme as a treatment of esophageal cancer, we treated mice bearing xenografts of the Colo680N (squamous carcinoma) and Bic1 (adenocarcinoma) cell lines using C93, a rationally designed molecule that inhibits FAS activity. In these experiments, C93 significantly inhibited the growth of orthotopic xenograft tumors from without causing anorexia and weight loss in the treated animals. We conclude that, similar to several other common types of human cancer, FAS is expressed at very high levels in esophageal cancer, and growth of these cancers can be inhibited by pharmacological agents that target this enzyme. Moreover, this high expression of FAS is also seen in pre-invasive lesions of the esophagus, leading us to propose considering of FAS-inhibitors for purposes of esophageal cancer chemoprevention. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5457.

Activity of some enzymes and electrolyte concentration in students’ serum of region of smelter Ferronikel in Glogovc – Kosovo

The triangle Mitrovica‐Obiliq‐Gllogovc is considered among the most polluted regions in Europe with heavy metals and toxic gases (WHO, 2002, Lunchakom P. et al. 2008). In blood serum of students exposed to pollution by the Ferronikeli smelter in Glogovc, the activity of enzymes has been investigated: alkaline phosphatase (FA), asparat aminotranspherase (AST), alanin aminotranspherase (ALT), and the concentration of electrolytes (K+, Na+, Cl−, total Ca, PO43− and Fe++). As a control group was taken a student group of the same age in Gjakova, located far from Ferronikeli. Preliminary results of research show the higher activity in significant scale of FA and significant lower values activity of AST, ALT and concentration Fe++, Cl−, total Ca++, compared with their respective values registered in the serum of control group. There is no difference between analyzed groups regarding the concentration of K+, Na+ and PO43. With the exception of FA, analyzed parameters do not exceed reference values, but in students from Gllogovc they are near the lower scale of allowed level, while in students of Gjakova near the above allowed level of the reference values.

Study of acute hepatotoxicity of Equisetum arvense L. in rats

To evaluate the acute hepatotoxicity of Equisentum arvense L. in rats. Fifty Wistar rats were used, these being divided in four groups, one being the control (receiving only water) and the other groups receiving graded doses of Equisentum arvense L. (30, 50, and 100mg/kg respectively) for 14 days. Blood samples were obtained to determine TGO, TGP, FA, DHL and GT-gamma activities. After that, hepatic tissue samples were collected for the anatomopathologic analysis. The anatomopathologic exam of the hepatic tissue showed organ with preserved lobular structure. In the same way, there was no significant change in the seric activities of the hepatic enzymes when compared to control group. The oral treatment with graded doses of Equisentum arvense L. was not able to produce hepatic changes. Further studies are necessary to evaluate the chronic hepatotoxicity of Equisentum arvense L. in rats.

Membrane-bound Fas ligand only is essential for Fas-induced apoptosis

Fas ligand (FasL), an apoptosis-inducing member of the TNF cytokine family and its receptor, Fas, are critical for shutdown of chronic immune responses1-3 and prevention of autoimmunity4,5. Accordingly, mutations in their genes cause severe lymphadenopathy and autoimmune disease in mice6,7 and humans8,9. FasL function is regulated by deposition in the plasma membrane and metalloprotease-mediated shedding10,11. We generated gene-targeted mice that selectively lack either secreted FasL (ΔsFasL) or membrane-bound FasL (ΔmFasL) to resolve which of these forms is required for cell killing and to explore their hypothetical non-apoptotic activities. Mice lacking sFasL (FasLΔs/Δs) appeared normal and their T cells readily killed target cells, whereas T cells lacking mFasL (FasLΔm/Δm) could not kill cells through Fas activation. FasLΔm/Δm mice developed lymphadenopathy and hyper-gammaglobulinaemia, similar to FasLgld/gld mice, which express a mutant form of FasL that cannot bind Fas, but surprisingly, (on a C57BL/6 background) FasLΔm/Δm mice succumbed to SLE-like autoimmune kidney destruction and histiocytic sarcoma, diseases that occur only rarely and considerably later in FasLgld/gld mice. These results demonstrate that mFasL is essential for cytotoxic activity and constitutes the guardian against lymphadenopathy, autoimmunity and cancer whereas excess sFasL appears to promote autoimmunity and tumorigenesis through non-apoptotic activities.

A computational study of the carboxylic acid of phloroglucinol in vacuo and in water solution

Abstract2,4,6‐Trihydroxybenzoic acid (FA) is the carboxylic acid of phloroglucinol and, in turn, the parent compound of many biologically active compounds. The biological activities of FA are “extreme” among trihydroxybenzoic acids (e.g., lowest antioxidant activity, highest toxicity toward crustaceans). A complete MP2/6‐31++G(d,p) conformational study in vacuo shows that the lowest energy conformers contain two intramolecular hydrogen bonds between the COOH function and the two ortho phenolic OH, with the Z form of COOH preferred over the E form. Comparisons with conformers in which the H‐bonds are removed enable fairly reliable evaluations of their energy, because of an off‐plane shift of COOH on H‐bond removal, decreasing the effects of lone pair repulsion. Comparisons with the other hydroxybenzoic acids (extensively calculated in vacuo at the same level of theory) suggest that FA has the strongest intramolecular H‐bonds. PCM calculations of FA in water solution show the same sequence of relative stabilities as in vacuo, with narrower differences because of the greater solvent stabilization of higher energy conformers. Calculations of adducts with water molecules H‐bonded to different donor–acceptor centers of FA show the preferred arrangements of water molecules around the different regions of FA and confirm that the stronger intramolecular H‐bonds are not broken on competition with the possibility of formation of intermolecular H‐bonds. HF/6‐31++G(d,p) calculations of adducts, in which the FA molecule is completely surrounded by water molecules, show that 14–16 water molecules (depending on the FA conformer geometry) realize arrangements corresponding to a presumable first solvation layer, with all the water molecules directly H‐bonded to donor–acceptor centers of FA or bridging water molecules directly H‐bonded to them. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

Bovine ephemeral fever virus-induced apoptosis requires virus gene expression and activation of Fas and mitochondrial signaling pathway

Bovine ephemeral fever virus-induced apoptosis requires virus gene expression and activation of Fas and mitochondrial signaling pathway

Bovine ephemeral fever virus-induced apoptosis requires virus gene expression and activation of Fas and mitochondrial signaling pathway

Although induction of apoptosis by bovine ephemeral fever virus (BEFV) in several cell lines has been previously demonstrated by our laboratory, less information is available on the process of BEFV-induced apoptosis in terms of cellular pathways and specific proteins involved. In order to determine the step in viral life cycle at which apoptosis of infected cells is triggered, chemical and physical agents were used to block viral infection. Treatment of BHK-21 infected cells with ammonium chloride (NH4Cl) or cells infected with UV-inactivated BEFV was seen to abrogate virus apoptosis induction, suggesting that virus uncoating and gene expression are required for the induction of apoptosis. Using soluble death receptors Fc:Fas chimera to block Fas signaling, BEFV-induced apoptosis was inhibited in cells. BEFV infection of BHK-21 cells results in the Fas-dependent activation of caspase 8 and cleavage of Bid. This initiated the dissipation of the membrane potential and the release of cytochrome c but not AIF or Smac/DIABLO from mitochondrial into cytoplasm leading to activation of caspase 9. Combined activation of the death receptor and mitochondrial pathways results in activation of the downstream effecter caspase 3 leading to cleavage of PARP. Fas-mediated BEFV-induced apoptosis could be suppressed by the overexpression of Bcl-2 or by treatment with caspase inhibitors and soluble death receptors Fc:Fas chimera. Taken together, this study provided first evidence demonstrating that BEFV-induced apoptosis requires viral gene expression and occurs through the activation of Fas and mitochondrion-mediated caspase-dependent pathways.

Limited efficiency of endogenous interleukin-7 levels in T cell reconstitution during HIV-1 infection: will exogenous interleukin-7 therapy work?

Limited efficiency of endogenous interleukin-7 levels in T cell reconstitution during HIV-1 infection: will exogenous interleukin-7 therapy work?