Release of soluble and vesicular purine nucleoside phosphorylase from rat astrocytes and microglia induced by pro-inflammatory stimulation with extracellular ATP via P2X 7 receptors

Peña-Altamira, Luis Emiliano; Polazzi, Elisabetta; Giuliani, Patricia; Beraudi, Alina; Massenzio, Francesca; Mengoni, Ilaria; Poli, Alessandro; Zuccarini, Mariachiara; Ciccarelli, Renata; Iorio, Patrizia Di; Virgili, Marco; Monti, Barbara; Caciagli, Francesco

doi:10.1016/j.neuint.2017.10.010

Cited by 24 publications

(25 citation statements)

References 72 publications

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“…Interestingly, upon LPS stimulation proteins related to RNA processing and protein translation were upregulated in the EVs ( Yang et al, 2018a ). Furthermore, glial microvesicles can contain purine nucleoside phosphorylase, a crucial enzyme in purine metabolism which converts ribonucleosides into purine bases and it can be released into the extracellular space through P2X 7 R activation, indicating that glial cells may support neuronal activity by maintaining the homeostasis of the purinergic system ( Pena-Altamira et al, 2018 ). Serotonin can also stimulate exosome release both in primary microglia cultures and BV2 cell lines ( Glebov et al, 2015 ).…”

Section: Microglial Communication By Extracellular Vesiclesmentioning

confidence: 99%

Bidirectional Microglia–Neuron Communication in Health and Disease

Szepesi

Manouchehrian²,

Bachiller³

et al. 2018

Front. Cell. Neurosci.

358

293

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Microglia are ramified cells that exhibit highly motile processes, which continuously survey the brain parenchyma and react to any insult to the CNS homeostasis. Although microglia have long been recognized as a crucial player in generating and maintaining inflammatory responses in the CNS, now it has become clear, that their function are much more diverse, particularly in the healthy brain. The innate immune response and phagocytosis represent only a little segment of microglia functional repertoire that also includes maintenance of biochemical homeostasis, neuronal circuit maturation during development and experience-dependent remodeling of neuronal circuits in the adult brain. Being equipped by numerous receptors and cell surface molecules microglia can perform bidirectional interactions with other cell types in the CNS. There is accumulating evidence showing that neurons inform microglia about their status and thus are capable of controlling microglial activation and motility while microglia also modulate neuronal activities. This review addresses the topic: how microglia communicate with other cell types in the brain, including fractalkine signaling, secreted soluble factors and extracellular vesicles. We summarize the current state of knowledge of physiological role and function of microglia during brain development and in the mature brain and further highlight microglial contribution to brain pathologies such as Alzheimer’s and Parkinson’s disease, brain ischemia, traumatic brain injury, brain tumor as well as neuropsychiatric diseases (depression, bipolar disorder, and schizophrenia).

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Section: Microglial Communication By Extracellular Vesiclesmentioning

confidence: 99%

Bidirectional Microglia–Neuron Communication in Health and Disease

Szepesi

Manouchehrian²,

Bachiller³

et al. 2018

Front. Cell. Neurosci.

358

293

View full text Add to dashboard Cite

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“…Intracellular GUA derives from guanosine triphosphate (GTP) breakdown and represents the starting point of reactions deputed to maintain intracellular levels of GTP (purine salvage pathway). When intracellular levels of GUA are excessive, it may be transported outside the cells by specific transmembrane nucleobases transporters, although most of the extracellular GUA derives from the breakdown of the released GTP and it is generated by GUO in a reaction catalyzed by the purine nucleoside phosphorylase (PNP) ( Rathbone et al, 2008 ; Giuliani et al, 2016 , 2017 ; Peña-Altamira et al, 2017 ). On the contrary, GUA degradation to xanthine (Xan) is mediated by Guanine deaminase (GDA) or cypin ( Miyamoto et al, 1982 ), which has been regarded as one of the “intrinsic factors” that regulate dendrite morphology together with the small GTPases RhoA, Rac1, the β-catenin ( Yu and Malenka, 2004 ), PSD-95 ( Charych et al, 2006 ) and the calcium/calmodulin-dependent protein kinase II (CAMKII) ( Fink et al, 2003 ).…”

Section: Introductionmentioning

confidence: 99%

Uncovering the Signaling Pathway behind Extracellular Guanine-Induced Activation of NO System: New Perspectives in Memory-Related Disorders

et al. 2018

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Mounting evidence suggests that the guanine-based purines stand out as key player in cell metabolism and in several models of neurodegenerative disorders, such as Parkinson’s and Alzheimer’s diseases. Guanosine (GUO) and guanine (GUA) are extracellular signaling molecules derived from the breakdown of the correspondent nucleotide, GTP, and their intracellular and extracellular levels are regulated by the fine-tuned activity of two major enzymes, purine nucleoside phosphorylase (PNP) and guanine deaminase (GDA). Noteworthy, GUO and GUA, seem to play opposite roles in the modulation of cognitive functions, such as learning and memory. Indeed GUO, despite exerting neuroprotective, anti-apoptotic and neurotrophic effects, causes a decay of cognitive activities, whereas GUA administration in rats results in working memory improvement (prevented by L-NAME pre-treatment). This study was designed to investigate, in a model of SH-SY5Y neuroblastoma cell line, the signal transduction pathway activated by extracellular GUA. Altogether, our results showed that: (i) in addition to an enhanced phosphorylation of ASK1, p38 and JNK, likely linked to a non-massive and transient ROS production, the PKB/NO/sGC/cGMP/PKG/ERK cascade seems to be the main signaling pathway elicited by extracellular GUA; (ii) the activation of this pathway occurs in a pertussis-toxin sensitive manner, thus suggesting the involvement of a putative G protein coupled receptor; (iii) the GUA-induced NO production, strongly reduced by cell pre-treatment with L-NAME, is negatively modulated by the EPAC-cAMP-CaMKII pathway, which causes the over-expression of GDA that, in turn, reduces the levels of GUA. These molecular mechanisms activated by GUA may be useful to support our previous observation showing that GUA improves learning and memory functions through the stimulation of NO signaling pathway, and underscore the therapeutic potential of oral administration of guanine for treating memory-related disorders.

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“…Interestingly, also anti-inflammatory effect has been attributed to the release of active purine nucleoside phosphorylase associated to EVs released by microglia as a response to extracellular ATP. ATP accumulates in extracellular matrix during inflammatory events in the brain, and the secretion of active purine nucleoside phosphorylase would counteract the presence of purine signaling [20].…”

Section: Enzymatic Activity Of Extracellular Vesiclesmentioning

confidence: 99%

“…EVs are secreted from donor to recipient cells allowing intracellular communication, either in a paracrine or endocrine manner [19,20]. One of the examples of the latest was given by tumor cells that favor the formation of a pre-metastatic niche by releasing EVs [21].…”

Section: Introductionmentioning

confidence: 99%

Metabolic Nano-Machines: Extracellular Vesicles Containing Active Enzymes and Their Contribution to Liver Diseases

2019

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Purpose of Review The field of extracellular vesicles is growing exponentially because of the important role that these extracellular organelles had on cell to cell communication, triggering a large number of review compilations focusing on different aspects of their biology. Although their importance as effectors or potential biomarkers is well covered, the highlight of extracellular vesicles as carriers of active enzymes which have the capability to transform the surrounding media is less covered by bibliographic studies. In the present review, we focus our attention on enzymatic activity carried by vesicles, with special attention on their contribution to liver conditions. Recent Findings Extracellular vesicles are circulating membrane-bound entities, characterized by a specific cargo. This cargo depends on the parental cell and the stimulus that triggers their release. Interestingly, the cargo includes active enzymes which had the ability of transforming the extracellular environment. Among them, extracellular vesicles derived from hepatocytes harbor specific liver enzymes that may cause an impact in the surrounds and target cells. Summary In this review, we summarize different active enzymes described in extracellular vesicles and we focus on enzymatic activities associated to liver damage. Since their release increases under liver damage conditions, their activity impact could play a role in the pathogenesis of liver and liver-associated diseases. Numerous examples in different liver conditions provided evidence of the potential of extracellular vesicles as therapeutic targets.

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Release of soluble and vesicular purine nucleoside phosphorylase from rat astrocytes and microglia induced by pro-inflammatory stimulation with extracellular ATP via P2X 7 receptors

Cited by 24 publications

References 72 publications

Bidirectional Microglia–Neuron Communication in Health and Disease

Bidirectional Microglia–Neuron Communication in Health and Disease

Uncovering the Signaling Pathway behind Extracellular Guanine-Induced Activation of NO System: New Perspectives in Memory-Related Disorders

Metabolic Nano-Machines: Extracellular Vesicles Containing Active Enzymes and Their Contribution to Liver Diseases

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