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31.
Nicoletta Bodrato Luisa Franco Chiara Fresia Lucrezia Guida Cesare Usai Annalisa Salis Iliana Moreschi Chiara Ferraris Claudia Verderio Giovanna Basile Santina Bruzzone Sonia Scarf�� Antonio De Flora Elena Zocchi 《The Journal of biological chemistry》2009,284(22):14777-14787
Abscisic acid (ABA) is a phytohormone regulating important functions in
higher plants, notably responses to abiotic stress. Recently, chemical or
physical stimulation of human granulocytes was shown to induce production and
release of endogenous ABA, which activates specific cell functions. Here we
provide evidence that ABA stimulates several functional activities of the
murine microglial cell line N9 (NO and tumor necrosis factor-α
production, cell migration) through the second messenger cyclic ADP-ribose and
an increase of intracellular calcium. ABA production and release occur in N9
cells stimulated with bacterial lipopolysaccharide, phorbol myristate acetate,
the chemoattractant peptide f-MLP, or β-amyloid, the primary plaque
component in Alzheimer disease. Finally, ABA priming stimulates N9 cell
migration toward β-amyloid. These results indicate that ABA is a
pro-inflammatory hormone inducing autocrine microglial activation, potentially
representing a new target for anti-inflammatory therapies aimed at limiting
microglia-induced tissue damage in the central nervous system.Microglial cells are the monocyte/macrophage equivalent of the central
nervous system and represent the first line of defense in the brain, by
removing infectious agents and damaged cells
(1). Microglia can also release
a variety of trophic factors and cytokines able to regulate the communication
between neuronal and other glial cells and can contribute to tissue repair and
neuroprotection
(2–4).
Pathologic microglial activation, however, confers neurotoxic properties to
these cells, thereby causing neuronal degeneration
(5). Excessive activation of
microglia, under conditions of chronic inflammation, can contribute to the
pathogenesis of neurodegenerative diseases, such as multiple sclerosis and
Alzheimer and Parkinson diseases, by producing and releasing a number of
potentially cytotoxic substances, including pro-inflammatory cytokines and NO
(4,
6–8).
Therefore, identification of the molecular mechanisms underlying microglial
activation might lead to the development of new anti-inflammatory drugs for
the treatment of these diseases.Abscisic acid
(ABA)2 is a plant
hormone regulating important biological functions in higher plants, including
response to abiotic stress, control of stomatal closure, regulation of seed
dormancy, and germination (9).
Recently, ABA was shown to behave as an endogenous pro-inflammatory hormone in
human granulocytes (10),
stimulating several functional activities of these cells (migration,
phagocytosis, reactive oxygen species, and NO production) through a signaling
cascade that involves a protein kinase A-mediated ADP-ribosyl cyclase
phosphorylation and consequent overproduction of the universal Ca2+
mobilizer cyclic ADP-ribose (cADPR)
(11). This mechanism leads to
an increase of the intracellular Ca2+ concentration, which is
ultimately responsible for granulocyte activation
(10).The facts that microglial cells play a defensive role in the central
nervous system similar to that of granulocytes in other tissues and that cADPR
has been described as the second messenger involved in the activation of
microglia induced by lipopolysaccharide (LPS)
(12) prompted us to
investigate the effect of ABA in these cells.Indeed, exogenous ABA, at concentrations ranging from 250 nm to
20 μm, elicits functional activation of murine N9 cells,
stimulating TNF-α release and cell migration through activation of the
ADP-ribosyl cyclase CD38 and overproduction of cADPR. Moreover, N9 cells
produce and release ABA when stimulated with LPS, amyloid β-peptide
(βA), phorbol myristate acetate (PMA), or the chemoattractant peptide
f-MLP. These results indicate that ABA behaves as an endogenous,
pro-inflammatory hormone in murine microglia and provide a new target for
future investigations into the role of this hormone in inflammatory and
degenerative diseases of the central nervous system accompanied by microglial
activation. 相似文献
32.
Roberto Giorda M. Clara Bonaglia Silvana Beri Francesca Novara Jill Urquhart Claudio Zucca Susan Marelli Daniela Di Benedetto Girolamo A. Vitello Santina Reitano Francesca Bisulli Massimo Mastrangelo Luigina Spaccini Elena Fontana Jill Clayton-Smith Philippe Jonveaux Marco Seri Bernardo dalla Bernardina 《American journal of human genetics》2009,85(3):394-400
Submicroscopic copy-number variations make a considerable contribution to the genetic etiology of human disease. We have analyzed subjects with idiopathic mental retardation (MR) by using whole-genome oligonucleotide-based array comparative genomic hybridization (aCGH) and identified familial and de novo recurrent Xp11.22-p11.23 duplications in males and females with MR, speech delay, and a peculiar electroencephalographic (EEG) pattern in childhood. The size of the duplications ranges from 0.8–9.2 Mb. Most affected females show preferential activation of the duplicated X chromosome. Carriers of the smallest duplication show X-linked recessive inheritance. All other affected individuals present dominant expression and comparable clinical phenotypes irrespective of sex, duplication size, and X-inactivation pattern. The majority of the rearrangements are mediated by recombination between flanking complex segmental duplications. The identification of common clinical features, including the typical EEG pattern, predisposing genomic structure, and peculiar X-inactivation pattern, suggests that duplication of Xp11.22-p11.23 constitutes a previously undescribed syndrome. 相似文献
33.
Ectocellular CD38-catalyzed synthesis and intracellular Ca2+-mobilizing activity of cyclic ADP-ribose 总被引:1,自引:0,他引:1
Antonio De Flora Luisa Franco Lucrezia Guida Santina Bruzzone Elena Zocchi 《Cell biochemistry and biophysics》1998,28(1):45-62
CD38 is a type-II transmembrane glycoprotein occurring in several hematopoietic and mature blood cells as well as in other cell types, including neurons. Although classified as an orphan receptor, CD38 is also a bifunctional ectoenzyme that catalyzes both the conversion of NAD+ to nicotinamide and cyclic ADP-ribose (cADPR), via an ADP-ribosyl cyclase reaction, and also the hydrolysis of cADPR to ADP-ribose (hydrolase). Major unresolved questions concern the correlation between receptor and catalytic properties of CD38, and also the apparent contradiction between ectocellular generation and intracellular Ca2+-mobilizing activity of cADPR. Results are presented that provide some explanations to this topological paradox in two different cell types. In cultured rat cerebellar granule neurons, extracellular cADPR (either generated by CD38 or directly added) elicited an enhanced intracellular Ca2+ response to KCl-induced depolarization, a process that can be qualified as a Ca2+-induced Ca2+ release (CICR) mechanism. On the other hand, in the CD38+ human Namalwa B lymphoid cells, NAD+ (and thiol compounds as well) induced a two-step process of self-aggregation followed by endocytosis of CD38, which resulted in a shift of cADPR metabolism from the cell surface to the cytosol. Both distinctive types of cellular responses to extracellular NAD+ seem to be suitable to elicit changes in the intracellular Ca2+ homeostasis. 相似文献
34.
Bruzzone S Verderio C Schenk U Fedele E Zocchi E Matteoli M De Flora A 《Journal of neurochemistry》2004,89(1):264-272
Recently, a new system of astrocyte-neurone glutamatergic signalling has been identified. It is started in astrocytes by ectocellular, CD38-catalysed conversion of NAD(+) to the calcium mobilizer cyclic ADP-ribose (cADPR). This is then pumped by CD38 itself into the cytosol where the resulting free intracellular Ca(2+) concentration [Ca(2+)](i) transients elicit an increased release of glutamate, which can induce an enhanced Ca(2+) response in neighbouring neurones. Here, we demonstrate that co-culture of either cortical or hippocampal astrocytes with neurones results in a significant overexpression of astrocyte CD38 both on the plasma membrane and intracellularly. The causal role of neurone-released glutamate in inducing overexpression of astrocyte CD38 is demonstrated by two observations: first, in the absence of neurones, induction of CD38 in pure astrocyte cultures can be obtained with glutamate and second, it can be prevented in co-cultures by glutamate receptor antagonists. The neuronal glutamate-mediated effect of neurones on astrocyte CD38 expression is paralleled by increased intracellular cADPR and [Ca(2+)](i) levels, both findings indicating functionality of overexpressed CD38. These results reveal a new neurone-to-astrocyte glutamatergic signalling based on the CD38/cADPR system, which affects the [Ca(2+)](i) in both cell types, adding further complexity to the bi-directional patterns of communication between astrocytes and neurones. 相似文献
35.
Two theoretical models for the interpretation of the existing data of CH-stretching overtones' vibrational circular dichroism data are presented. The first model is based on the quantum mechanical Van Vleck contact transformation theory and is applied to the full vibrational problem, the second is based on classical trajectories calculations, by which we treat a simplified three-degrees of freedom Hamiltonian. The latter allows one to derive a qualitative but efficacious picture of the behavior of coupled anharmonic oscillators. In this framework, we analyze the Poincare Surfaces of Section, and calculate the Fourier Cross Spectra of coupled CH-stretchings. Values for the harmonic frequencies and anharmonicities are derived from absorption spectra in the near infrared on partially deuterated compounds. The effect of large amplitude, low-frequency puckering or twisting modes on the ensemble of coupled CH-stretching is taken into account. Copyright 2000 Wiley-Liss, Inc. 相似文献
36.
Studies indicate that phosphorylated Bcl-2 cannot form a heterodimer with Bax and thus may lose its antiapoptotic potential. The present study tests the hypothesis that graded hypoxia in cerebral tissue induces the phosphorylation of Bcl-2, thus altering the heterodimerization of Bcl-2 with Bax and subsequently leading to apoptosis. Anesthetized, ventilated newborn piglets were assigned to a normoxic and a graded hypoxic group. Cerebral cortical neuronal nuclei were isolated and immunoprecipitated; immune complexes were separated and reacted with Bcl-2 and Bax specific antibodies. The results show an increased level of serine/tyrosine phosphorylated Bcl-2 in nuclear membranes of hypoxic animals. The level of phosphorylated Bcl-2 protein increased linearly with decrease in tissue PCr. The level of phosphorylated Bax in the neuronal nuclear membranes was independent of cerebral tissue PCr. The data shows that during hypoxia, there is increased phosphorylation of Bcl-2, which may prevent its heterodimerization with Bax and lead to increased proapoptotic activity due to excess Bax in the hypoxic brain. Further increased phosphorylation of Bcl-2 may alter the Bcl-2/Bax-dependent antioxidant, lipid peroxidation and pore forming activity, as well as the regulation of intranuclear Ca2+ and caspase activation pathways. We speculate that increased phosphorylation of Bcl-2 in neuronal nuclear membranes is a potential mechanism of programmed cell death activation in the hypoxic brain. 相似文献
37.
Vanessa Ginet Julien Puyal Coralie Rummel Dominique Aubry Caroline Breton Anne-Julie Cloux Somi R Majjigapu Bernard Sordat Pierre Vogel Santina Bruzzone Alessio Nencioni Michel A Duchosal Aimable Nahimana 《Autophagy》2014,10(4):603-617
APO866, an inhibitor of NAD biosynthesis, exhibits potent antitumor properties in various malignancies. Recently, it has been shown that APO866 induces apoptosis and autophagy in human hematological cancer cells, but the role of autophagy in APO866-induced cell death remains unclear. Here, we report studies on the molecular mechanisms underlying APO866-induced cell death with emphasis on autophagy. Treatment of leukemia and lymphoma cells with APO866 induced both autophagy, as evidenced by an increase in autophagosome formation and in SQSTM1/p62 degradation, but also increased caspase activation as revealed by CASP3/caspase 3 cleavage. As an underlying mechanism, APO866-mediated autophagy was found to deplete CAT/catalase, a reactive oxygen species (ROS) scavenger, thus promoting ROS production and cell death. Inhibition of autophagy by ATG5 or ATG7 silencing prevented CAT degradation, ROS production, caspase activation, and APO866-induced cell death. Finally, supplementation with exogenous CAT also abolished APO866 cytotoxic activity. Altogether, our results indicated that autophagy is essential for APO866 cytotoxic activity on cells from hematological malignancies and also indicate an autophagy-dependent CAT degradation, a novel mechanism for APO866-mediated cell killing. Autophagy-modulating approaches could be a new way to enhance the antitumor activity of APO866 and related agents. 相似文献
38.
Simone Cappello Giuseppe Mancini Alessandro Pistone Maurizio Azzaro Francesco Bottino Lucrezia Genovese Daniela Iannazzo Antonella Luciano Antonino Mamo Giovanni Neri Signorino Galvagno Santina Santisi Annamaria Visco Michail M. Yakimov 《Reviews in Environmental Science and Biotechnology》2014,13(4):369-375
Throughout the last century the increasing human activities in Antarctic region, particularly research expeditions, fishing, and tourism amplified the risk of oils spills at these high latitudes of the meridional hemisphere. A number of studies have been focused on chronic hydrocarbon contamination near Antarctic research stations revealing the presence and persistence of these human-derived contaminants. Marine ship-source oil spills in Antarctic region can have significant impacts on the marine environment. The key factors to effectively fight oil spills are a careful selection and proper use of the equipment and materials best suited to the critical local conditions. Despite the significant advances in the field of environmental recovery after an “oil spill” episode, research has recently shown that the usual techniques are often less effective than expected. This issue become much more relevant in the Antarctic case, not only for the incomparable environmental value of the Antarctic region but also for the extreme environmental conditions and the great distances from properly equipped centers, that make unfeasible sending naval vessels. Scope of the STRANgE Project is the preliminary design of a prototype floating platform, parachutable by plane, able to intervene as quickly as possible for the containment, removal and treatment/storage of the oil slick. New sorbent nanostructured materials and specialized Antarctic bacteria applications constitute the main innovations of this Project. 相似文献
39.
Patrizia Albertano Gabriele Pinto Salvatore Santisi Roberto Taddei 《Plant biosystems》2013,147(2-3):65-76
Abstract A strain of the alga Spermatozopsis acidophila from highly acidic environments in the solfatara at Pisciarelli (Naples, Italy) has been studied from the ecological, physiological, morphological and ultrastructural points of view. Its pH optimum (1.0) and its upper limit of pH (1.8) are the lowest recorded for any algal species. Our ultrastructural investigation has confirmed that it belongs to the family Poly-blepharidaceae (Volvocales). A conspicuously developed chloroplast was noted, along with a remarkable quantity of microtubules and E. R. cisternae. 相似文献
40.
Zonal migration and trail‐following of an intertidal gastropod analyzed by led tracking in the field
G. Chelazzi R. Innocenti P. Della Santina 《Marine and Freshwater Behaviour and Physiology》2013,45(2):121-136
A new technique is described for the continuous recording of the movements of intertidal molluscs in the field. Photographic monitoring of snails equipped with LEDs powered by small batteries revealed that the prosobranch gastropod Nerita textilis adopts a hybrid (zonal‐homing) pattern including a definite trail‐following behaviour. The method allowed the study of individual feeding migrations in terms of speed and orientation of the snails at different moments of the tidal cycle. The application of the LED technique to other molluscs and nocturnal animals is discussed. Nocturnal arena tests performed to complete the field observations confirmed the presence of interindividual and self‐trailing in N. textilis but not in the related sympatric species N. plicata. The behaviour of N. textilis is compared to that of other intertidal molluscs. 相似文献