2,3,7,8-Tetrachlorodibenzo-p-dioxin regulates Bovine Herpesvirus type 1 induced apoptosis by modulating Bcl-2 family members

Fiorito, Filomena; Marfè, Gabriella; Blasio, E. De; Granato, Giovanna Elvira; Tafani, Marco; Martino, Luisa De; Montagnaro, Serena; Florio, Salvatore; Pagnini, Ugo

doi:10.1007/s10495-008-0249-y

Cited by 33 publications

(46 citation statements)

References 36 publications

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“…In agreement with our previous reports [9], [50], [51], in the present study we first confirmed that TCDD induce a significant time and dose dependent viability decrease of BHV-1 infected cells. This effect is likely linked to a cell increased susceptibility to viral infection induced by the dioxin exposure, as described later.…”

Section: Discussionsupporting

confidence: 94%

“…Considering the concomitant widespread environmental diffusion of both dioxin and BHV-1, within a broader research project aimed to investigate the biological effects of dioxin in mammalian cells, herein we have explored the combined effects of TCDD exposure and BHV-1 infection on cellular iron metabolism. In particular, we focused on the possible impact of TCDD-dependent iron metabolism dysregulation on the progression of virus infection in MDBK cells, a useful and standardized epithelial-like in vitro model to study both virus replication and TCDD exposure in mammalian cells [9], [38], [45], [49]–[51]. As well to get an insight into the regulation of cellular iron homeostasis in presence of environmental toxins, these studies may have important repercussions especially in those geographic areas where dioxin and BHV-1 are concomitantly widespread.…”

Section: Discussionmentioning

confidence: 99%

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2,3,7,8-Tetrachlorodibenzo-p-Dioxin Promotes BHV-1 Infection in Mammalian Cells by Interfering with Iron Homeostasis Regulation

et al. 2013

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Mammalian cells require iron to satisfy metabolic needs or to accomplish specialized functions, and DNA viruses, like bovine herpesvirus 1 (BHV-1), require an iron-replete host to efficiently replicate, so that iron bioavailability is an important component of viral virulence. Cellular iron metabolism is coordinately controlled by the Iron Regulatory Proteins (IRP1 and IRP2), whose activity is affected by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a current and persistent environmental contaminant. Considering that TCDD enhances BHV-1 replication, herein we analyzed the effects of TCDD on iron metabolism during BHV-1 infection in MDBK cells, and presented evidences of a divergent modulation of IRP1 and IRP2 RNA-binding capacity. Moreover, an up-regulation of transferrin receptor 1 (TfR1) and a concomitant down-regulation of ferritin were observed. This scenario led to an expansion of the labile iron pool (LIP) and induces a significant enhance of viral titer, as confirmed by increased levels of BHV-1 infected cell protein 0 (bICP0), the major transcriptional regulatory protein of BHV-1. Taken together, our data suggest that TCDD increases the free intracellular iron availability thereby promoting the onset of BHV-1 infection and rendering bovine cells more vulnerable to the virus.

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Section: Discussionsupporting

confidence: 94%

Section: Discussionmentioning

confidence: 99%

2,3,7,8-Tetrachlorodibenzo-p-Dioxin Promotes BHV-1 Infection in Mammalian Cells by Interfering with Iron Homeostasis Regulation

et al. 2013

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“…Forced expression of the Bcl‐2 gene attenuated TCDD‐caused apoptosis of HUVECs, along with suppression of caspase 3 activity. In agreement with our observations, TCDD also promotes apoptosis of human trophoblast‐like JAR cells 53 and bovine MDBK cells 54 by down‐regulating expression of the Bcl‐2 gene. Given that EP3 inhibition or knockdown restored TCDD‐caused‐p38 MAPK activation and suppressed Bcl‐2 expression, EP3‐mediated activation of the p38MAPK/Bcl‐2 pathway contributes to apoptosis increased by TCDD in HUVECs.…”

Section: Discussionsupporting

confidence: 92%

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

Liu

Guo

et al. 2017

J Cellular Molecular Medi

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Endothelial injury or dysfunction is an early event in the pathogenesis of atherosclerosis. Epidemiological and animal studies have shown that 2, 3, 7, 8‐tetrachlorodibenzo‐p‐dioxin (TCDD) exposure increases morbidity and mortality from chronic cardiovascular diseases, including atherosclerosis. However, whether or how TCDD exposure causes endothelial injury or dysfunction remains largely unknown. Cultured human umbilical vein endothelial cells (HUVECs) were exposed to different doses of TCDD, and cell apoptosis was examined. We found that TCDD treatment increased caspase 3 activity and apoptosis in HUVECs in a dose‐dependent manner,at doses from 10 to 40 nM. TCDD increased cyclooxygenase enzymes (COX)‐2 expression and its downstream prostaglandin (PG) production (mainly PGE2 and 6‐keto‐PGF1α) in HUVECs. Interestingly, inhibition of COX‐2, but not COX‐1, markedly attenuated TCDD‐triggered apoptosis in HUVECs. Pharmacological inhibition or gene silencing of the PGE2 receptor subtype 3 (EP3) suppressed the augmented apoptosis in TCDD‐treated HUVECs. Activation of the EP3 receptor enhanced p38 MAPK phosphorylation and decreased Bcl‐2 expression following TCDD treatment. Both p38 MAPK suppression and Bcl‐2 overexpression attenuated the apoptosis in TCDD‐treated HUVECs. TCDD increased EP3‐dependent Rho activity and subsequently promoted p38MAPK/Bcl‐2 pathway‐mediated apoptosis in HUVECs. In addition, TCDD promoted apoptosis in vascular endothelium and delayed re‐endothelialization after femoral artery injury in wild‐type (WT) mice, but not in EP3−/− mice. In summary, TCDD promotes endothelial apoptosis through the COX‐2/PGE2/EP3/p38MAPK/Bcl‐2 pathway. Given the cardiovascular hazard of a COX‐2 inhibitor, our findings indicate that the EP3 receptor and its downstream pathways may be potential targets for prevention of TCDD‐associated cardiovascular diseases.

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“…Our data agree with results of Gautier et al [] who described induction of apoptosis in neuronlike cells infected with HSV‐1 at early stage of infections, with the results of Xu et al [] which reported similar findings for BHV‐1 infection in MDBK cell line and with several studies that reported concomitant caspase‐8 and caspase‐9 activation in various apoptotic systems [Aubert et al, ; St‐Louis and Archambault, ; Fiorito et al, ; Longo et al, ].…”

Section: Discussionsupporting

confidence: 93%

Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line

Montagnaro

Ciarcia

Martinis

et al. 2013

J of Cellular Biochemistry

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Caprine herpesvirus type 1 (CpHV-1), like other members of the alpha subfamily of herpesviruses, establishes latent infections in trigeminal ganglion neurons. Our groups previously demonstrated that CpHV-1 induces apoptosis in goat peripheral blood mononuclear cells and in an epithelial bovine cell line, but the ability of CpHV-1 to induce apoptosis in neuronal cells remains unexplored. In this report, the susceptibility of Neuro 2A cells to infection by CpHV-1 was examined. Following infection of cultured cells with CpHV-1, expression of cell death genes was evaluated using real-time PCR and Western blot assays. Analysis of virus-infected cells revealed activation of caspase-8, a marker for the extrinsic pathway of apoptosis, and caspase-9, a marker for the intrinsic pathway of apoptosis at 12 and 24 h post-infection. Significant increase in the levels of cleaved caspase-3 was also observed at the acme of cytopathic effect at 24 h post-infection. In particular, at 3 and 6 h post-infection, several proapototic genes were under-expressed. At 12 h post-infection several proapototic genes such as caspases, TNF, Cd70, and Traf1 were over expressed while Bcl2a1a, Fadd, and TNF genes were underexpressed. In conclusion, the simultaneous activation of caspase-8 and caspase-9 suggests that CpHV-1 can trigger the death-receptor pathway and the mitochondrial pathway separately and in parallel. Our findings are significant because this is the first published study showing the effect of CpHV-1 infection in neuronal cells in terms of gene expression and apoptosis modulation.

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2,3,7,8-Tetrachlorodibenzo-p-dioxin regulates Bovine Herpesvirus type 1 induced apoptosis by modulating Bcl-2 family members

Cited by 33 publications

References 36 publications

2,3,7,8-Tetrachlorodibenzo-p-Dioxin Promotes BHV-1 Infection in Mammalian Cells by Interfering with Iron Homeostasis Regulation

2,3,7,8-Tetrachlorodibenzo-p-Dioxin Promotes BHV-1 Infection in Mammalian Cells by Interfering with Iron Homeostasis Regulation

2, 3, 7, 8‐Tetrachlorodibenzo‐p‐dioxin promotes endothelial cell apoptosis through activation of EP3/p38MAPK/Bcl‐2 pathway

Modulation of apoptosis by caprine herpesvirus 1 infection in a neuronal cell line

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