Involvement of interferon-alpha in the regulation of apoptosis of cells of the hypothalamo-hypophyseal-adrenocortical system of aged mice in oxidative stress

Бажанова, Е. Д.; Teplyi, D. L.

doi:10.1007/s11055-005-0035-z

Cited by 3 publications

(2 citation statements)

References 11 publications

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“…. The recognised implications of α‐interferon and of TNF‐α in triggering oxidative stress faced with the up‐regulation of their transcripts altogether provide an additional support to an overall pro‐oxidant state in FA patients. This finding is consistent with the previous reports supporting the view that cytokine hypersensitivity of FA haematopoietic cells is one of the major factors in the pathogenesis of bone marrow failure in FA , consistent with excess ROS production by TNF‐α at inflammatory sites inducing oxidative DNA damages in FA cells .…”

Section: Discussionmentioning

confidence: 96%

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways

Pagano¹,

Talamanca²,

Castello³

et al. 2013

European J of Haematology

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Fanconi anaemia (FA) is a genetic cancer predisposition disorder associated with cytogenetic instability, bone marrow failure and a pleiotropic cellular phenotype, including low thresholds of responses to oxidative stress, cross-linking agents and selected cytokines. This study was aimed at defining the scope of abnormalities in gene expression using the publicly available FA Transcriptome Consortium (FTC) database (Gene Expression Omnibus, 2009 and publicly available as GSE16334). We evaluated the data set that included transcriptomal analyses on RNA obtained from low-density bone marrow cells (BMC) from 20 patients with FA and 11 healthy volunteers, by seeking to identify changes in expression of over 22,000 genes, including a set of genes involved in: (i) bioenergetic pathways; (ii) antioxidant activities; (iii) response to stress and metal-chelating proteins; (iv) inflammation-related cytokines and (v) DNA repair. Ontological analysis of genes expressed at magnitudes of 1.5-fold or greater demonstrated significant suppression of genes in the categories of (i) energy metabolism; (ii) antioxidant activities; and (iii) stress and chelating proteins. Enhanced expression was found for 16 of 26 genes encoding inflammatory cytokines. A set of 20 of 21 transcripts for DNA repair activities were down-regulated; four of these transcripts related to type II topoisomerase. The data provide evidence for alterations in gene regulation of bioenergetic activities, redox-related activities, stress and metal-chelating proteins, and of some selected DNA repair activities in patients with FA.

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Section: Discussionmentioning

confidence: 96%

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways

Pagano¹,

Talamanca²,

Castello³

et al. 2013

European J of Haematology

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“…While IFNβis known to have potent proapoptotic effects (58), promoting apoptosis in several cancer (49, 50) and immune cells (47, 48), IFNα activates different downstream targets to prevent apoptosis in endothelial cells (40) and neuronal tissue (8). IFNα has also previously been reported to protect against apoptosis and promote barrier integrity in polarized intestinal epithelial cell monolayers (46).…”

Section: Discussionmentioning

confidence: 99%

Commensal Escherichia coli Reduces Epithelial Apoptosis through IFN-αA–Mediated Induction of Guanylate Binding Protein-1 in Human and Murine Models of Developing Intestine

Mirpuri

Brazil

Berardinelli

et al. 2010

The Journal of Immunology

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Summary Appropriate microbial colonization protects the developing intestine by promoting epithelial barrier function and fostering mucosal tolerance to luminal bacteria. Commensal flora mediate their protective effects through TLR9-dependent activation of cytokines such as type I IFNs (α,β) and IL-10. While IFNβ promotes apoptosis, IFNα activates specific anti-apoptotic target genes whose actions preserve epithelial barrier integrity. We have recently identified guanylate binding protein-1 (GBP-1) as an anti-apoptotic protein, regulated by both type I and type II IFNs, that promotes intestinal epithelial barrier integrity in mature intestine. However, the mechanisms by which commensal bacteria regulate epithelial apoptosis during colonization of immature intestine and the contributions of GBP-1 are unknown. The healthy newborn intestine is initially colonized with bacterial species present in the maternal GI tract, including non-pathogenic E. coli. Therefore, we examined the influence of commensal E. coli on cytokine expression and candidate mediators of apoptosis in preweaned mice. Specifically, enteral exposure of 2 week-old mice to commensal E. coli for 24 hours selectively increased both IFNαA and GBP-1 mRNA expression and prevented staurosporine-induced epithelial apoptosis. Exogenous IFNαA treatment also induced GBP-1 expression and protected against staurosporine-induced apoptosis in a GBP-1 dependent manner, both in vitro and ex vivo. These findings identify a role for IFNαA-mediated GBP-1 expression in the prevention of intestinal epithelial apoptosis by commensal bacteria. Thus IFNαA mediates the beneficial effects of commensal bacteria and may be a promising therapeutic target to promote barrier integrity and prevent the inappropriate inflammatory responses seen in developing intestine as in Necrotizing Enterocolitis (NEC).

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Hyperoxic Brain Effects Are Normalized by Addition of CO2

2007

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BackgroundHyperoxic ventilation (>21% O2) is widely used in medical practice for resuscitation, stroke intervention, and chronic supplementation. However, despite the objective of improving tissue oxygen delivery, hyperoxic ventilation can accentuate ischemia and impair that outcome. Hyperoxia results in, paradoxically, increased ventilation, which leads to hypocapnia, diminishing cerebral blood flow and hindering oxygen delivery. Hyperoxic delivery induces other systemic changes, including increased plasma insulin and glucagon levels and reduced myocardial contractility and relaxation, which may derive partially from neurally mediated hormonal and sympathetic outflow. Several cortical, limbic, and cerebellar brain areas regulate these autonomic processes. The aim of this study was to assess recruitment of these regions in response to hyperoxia and to determine whether any response would be countered by addition of CO2 to the hyperoxic gas mixture.Methods and FindingsWe studied 14 children (mean age 11 y, range 8–15 y). We found, using functional magnetic resonance imaging, that 2 min of hyperoxic ventilation (100% O2) following a room air baseline elicited pronounced responses in autonomic and hormonal control areas, including the hypothalamus, insula, and hippocampus, throughout the challenge. The addition of 5% CO2 to 95% O2 abolished responses in the hypothalamus and lingual gyrus, substantially reduced insular, hippocampal, thalamic, and cerebellar patterns in the first 48 s, and abolished signals in those sites thereafter. Only the dorsal midbrain responded to hypercapnia, but not hyperoxia.ConclusionsIn this group of children, hyperoxic ventilation led to responses in brain areas that modify hypothalamus-mediated sympathetic and hormonal outflow; these responses were diminished by addition of CO2 to the gas mixture. This study in healthy children suggests that supplementing hyperoxic administration with CO2 may mitigate central and peripheral consequences of hyperoxia.

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Involvement of interferon-alpha in the regulation of apoptosis of cells of the hypothalamo-hypophyseal-adrenocortical system of aged mice in oxidative stress

Cited by 3 publications

References 11 publications

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways

Bone marrow cell transcripts from Fanconi anaemia patients reveal in vivo alterations in mitochondrial, redox and DNA repair pathways

Commensal Escherichia coli Reduces Epithelial Apoptosis through IFN-αA–Mediated Induction of Guanylate Binding Protein-1 in Human and Murine Models of Developing Intestine

Hyperoxic Brain Effects Are Normalized by Addition of CO2

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