1,721,001 research outputs found
GD3 in cellular ageing and apoptosis
No full textLipid and glycolipid mediators are important components of the adaptive responses to stress, including apoptosis. In mammalian cells, the intracellular accumulation of ganglioside GD3, an acidic glycosphingolipid, contributes to mitochondrial damage, a crucial event during the apoptotic program. GD3 is a minor ganglioside in most normal tissues. Its expression increases during development and in pathological conditions such as cancer and neurodegenerative disorders. Interestingly, GD3 expression also increases with the normal ageing process. Moreover, GD3 can also mediate biological events like proliferation and differentiation. Since organism integrity requires a tight balance between cell proliferation, apoptosis and senescence, controlling the intracellular level of GD3 appears of particular importance for cell fate determination
The ganglioside GD3 as the greek goddess Hecate: Several faces turned towards as many directions
No full textThe disialoganglioside GD3 can mediate biological functions as diverse as proliferation, differentiation, and apoptosis. Since intracellular level of GD3 is crucial for the cell, understanding the mechanisms by which GD3 metabolism is tightly regulated seems of particular importance. GD3 can be enlisted among the most potent natural inducers of mitochondrial damage and apoptosis. However, some cell types resist GD3-mediated mitochondrial damage through complex mechanisms which are beginning to be unveiled. © 2005 IUBMB
GD3 ganglioside directly targets mitochondria and induces the release of apoptogenic factors
Full text linkLipid and glycolipid diffusible mediators
are involved in the intracellular progression and
amplification of apoptotic signals. GD3 ganglioside
is rapidly synthesized from accumulated ceramide
after the clustering of death-inducing receptors and
triggers apoptosis. Here we show that GD3 induces
dissipation of DCm and swelling of isolated mitochondria,
which results in the mitochondrial release
of cytochrome c, apoptosis inducing factor, and
caspase 9. Soluble factors released from GD3-
treated mitochondria are sufficient to trigger DNA
fragmentation in isolated nuclei. All these effects can
be blocked by cyclosporin A, suggesting that GD3 is
acting at the level of the permeability transition pore
complex. We found that endogenous GD3 accumulates
within mitochondria of cells undergoing apoptosis
after ceramide exposure. Accordingly, suppression
of GD3 synthase (ST8) expression in intact
cells substantially prevents ceramide-induced DCm
dissipation, indicating that endogenously synthesized
GD3 induces mitochondrial changes in vivo. Finally,
enforced expression of bcl-2 significantly prevents
GD3-induced mitochondrial changes, caspase 9 activation,
and apoptosis. These results show that mitochondria
are a key destination for apoptogenic GD3
ganglioside along the lipid pathway to programmed
cell death and indicate that relevant GD3 targets are
under bcl-2 control.—Rippo, M. R., Malisan, F.,
Ravagnan, L., Tomassini, B., Condo, I., Costantini,
P., Susin, S. A., Rufini, A., Todaro, M., Kroemer, G.,
Testi, R. GD3 ganglioside directly targets mitochondria
in a bcl-2-controlled fashion
GD3 ganglioside and apoptosis
No full textLipid and glycolipid mediators are important messengers of the adaptive responses to stress, including apoptosis. In mammalian cells, the intracellular accumulation of ganglioside GD3, an acidic glycosphingolipid, contributes to mitochondrial damage, a crucial event during the apoptopic program. GD3 is a minor ganglioside in most normal tissues. Its expression increases during development and in pathological conditions such as cancer and neurodegenerative disorders. Intriguingly, GD3 can mediate additional biological events such as cell proliferation and differentiation. These diverse and opposing effects indicate that tightly regulated mechanisms, including 9-O-acetylation, control GD3 function, by affecting intracellular levels, localization and structure of GD3, and eventually dictate biological outcomes and cell fate decisions. © 2002 Elsevier Science B.V. All rights reserved
Ceramide catabolism critically controls survival of human dendritic cells
No full textThe regulation of dendritic cell (DC) survival is crucial for the modulation of adaptive immunity. Ceramide is a lipid mediator of the stress response, which accumulates intracellularly during DC differentiation. We found that ceramide levels are tightly regulated in human DCs and that the pharmacological inhibition of enzymes responsible for ceramide catabolism, such as ceramidases and sphingosine kinases, sensitizes DCs to ceramide-induced cell death. It is important that inhibition of sphingosine kinases, during lipopolysaccharide stimulation, causes extensive ceramide accumulation and death of DCs. These data indicate that ceramide catabolism regulates survival of human DCs and reveal novel potential targets for the pharmacological manipulation of the immune response
A pool of extramitochondrial frataxin that promotes cell survival
No full textFrataxin is a mitochondrial protein involved in iron metabolism. Defective expression of frataxin causes Friedreich ataxia (FA), an inherited degenerative syndrome characterized by ataxia, cardiomyopathy, and high incidence of diabetes. Here we report that frataxin-deficient cells are more prone to undergo stress-induced mitochondrial damage and apoptosis, while the overexpression of frataxin confers protection to a variety of cell types. Moreover, we reveal the existence of an extramitochondrial pool of frataxin, which can efficiently prevent mitochondrial damage and apoptosis in different cellular systems. Remarkably, extramitochondrial frataxin can fully replace mitochondrial frataxin in promoting survival of FA cells
Interferon gamma upregulates frataxin and corrects the functional deficits in a Friedreich ataxia model
Full text linkCopyright © The Author 2012. Published by Oxford University Press.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/2.5), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.Friedreich's ataxia (FRDA) is the most common hereditary ataxia, affecting ∼3 in 100 000 individuals in Caucasian populations. It is caused by intronic GAA repeat expansions that hinder the expression of the FXN gene, resulting in defective levels of the mitochondrial protein frataxin. Sensory neurons in dorsal root ganglia (DRG) are particularly damaged by frataxin deficiency. There is no specific therapy for FRDA. Here, we show that frataxin levels can be upregulated by interferon gamma (IFNγ) in a variety of cell types, including primary cells derived from FRDA patients. IFNγ appears to act largely through a transcriptional mechanism on the FXN gene. Importantly, in vivo treatment with IFNγ increases frataxin expression in DRG neurons, prevents their pathological changes and ameliorates the sensorimotor performance in FRDA mice. These results disclose new roles for IFNγ in cellular metabolism and have direct implications for the treatment of FRDA.AtaxiaUK, National Ataxia Foundation, USA, Friedreich Ataxia Research Alliance
(FARA), USA and Telethon-Italy, FARA, GoFAR, the Wellcome
Trust, the EU FP7 and the Fondazione Telethon
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Full text link“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
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