Mechanisms of P2X7 receptor-mediated ERK1/2 phosphorylation in human astrocytoma cells

2003 ◽  
Vol 284 (2) ◽  
pp. C571-C581 ◽  
Author(s):  
Fernand-Pierre Gendron ◽  
Joseph T. Neary ◽  
Patty M. Theiss ◽  
Grace Y. Sun ◽  
Fernando A. Gonzalez ◽  
...  

Astrocytes are involved in normal and pathological brain functions, where they become activated and undergo reactive gliosis. Astrocytes have been shown to respond to extracellular nucleotides via the activation of P2 receptors, either G protein-coupled P2Y receptors or P2X receptors that are ligand-gated ion channels. In this study, we have examined the manner in which activation of the P2X7 nucleotide receptor, an extracellular ATP-gated ion channel expressed in astrocytes, can lead to the phosphorylation of ERK1/2. Results showed that the P2X7 receptor agonist 2′,3′- O-(4-benzoyl)benzoyl-ATP induced ERK1/2 phosphorylation in human astrocytoma cells overexpressing the recombinant rat P2X7 receptor (rP2X7-R), a response that was inhibited by the P2X7 receptor antagonist, oxidized ATP. Other results suggest that rP2X7-R-mediated ERK1/2 phosphorylation was linked to the phosphorylation of the proline-rich/Ca2+-activated tyrosine kinase Pyk2, c-Src, phosphatidylinositol 3′-kinase, and protein kinase Cδ activities and was dependent on the presence of extracellular Ca2+. These results support the hypothesis that the P2X7 receptor and its signaling pathways play a role in astrocyte-mediated inflammation and neurodegenerative disease.

Steroids ◽  
2016 ◽  
Vol 105 ◽  
pp. 19-25 ◽  
Author(s):  
Ana Gabriela Piña-Medina ◽  
Valeria Hansberg-Pastor ◽  
Aliesha González-Arenas ◽  
Marco Cerbón ◽  
Ignacio Camacho-Arroyo

1991 ◽  
Vol 568 (1-2) ◽  
pp. 92-100 ◽  
Author(s):  
Jose L. Tomsig ◽  
Eric Gruenstein ◽  
Ruth V.W. Dimlich

2010 ◽  
Vol 2010 ◽  
pp. 1-10 ◽  
Author(s):  
Abdelkader Hamadi ◽  
Therese B. Deramaudt ◽  
Kenneth Takeda ◽  
Philippe Rondé

Cell adhesion and migration are key determinants in tumor metastasis. Adherence of tumor cell to the extracellular matrix is mediated via integrin containing focal adhesions (FAs). Binding of integrins to ECM triggers phosphorylation of two major components of FAs, focal adhesion kinase (FAK) and Src, activating downstream signaling pathway which leads to FA disassembly and cell migration. In this paper, we analyze how phosphorylation of FAK regulates its trafficking at FAs in living human astrocytoma cells. Upon pervanadate-induced FAK phosphorylation, phosphorylated FAK appeared highly expressed at newly formed membrane ruffles. This effect was abolished in presence of the specific Src inhibitor PP2. Our findings demonstrate that upon phosphorylation, FAK delocalizes from FAs to membrane ruffles.


Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 728 ◽  
Author(s):  
Trisha Barnard ◽  
Maaran Rajah ◽  
Selena Sagan

The recent emergence and rapid geographic expansion of Zika virus (ZIKV) poses a significant challenge for public health. Although historically causing only mild febrile illness, recent ZIKV outbreaks have been associated with more severe neurological complications, such as Guillain-Barré syndrome and fetal microcephaly. Here we demonstrate that two contemporary (2015) ZIKV isolates from Puerto Rico and Brazil may have increased replicative fitness in human astrocytoma cells. Over a single infectious cycle, the Brazilian isolate replicates to higher titers and induces more severe cytopathic effects in human astrocytoma cells than the historical African reference strain or an early Asian lineage isolate. In addition, both contemporary isolates induce significantly more double-stranded RNA in infected astrocytoma cells, despite similar numbers of infected cells across isolates. Moreover, when we quantified positive- and negative-strand viral RNA, we found that the Asian lineage isolates displayed substantially more negative-strand replicative intermediates than the African lineage isolate in human astrocytoma cells. However, over multiple rounds of infection, the contemporary ZIKV isolates appear to be impaired in cell spread, infecting a lower proportion of cells at a low MOI despite replicating to similar or higher titers. Taken together, our data suggests that contemporary ZIKV isolates may have evolved mechanisms that allow them to replicate with increased efficiency in certain cell types, thereby highlighting the importance of cell-intrinsic factors in studies of viral replicative fitness.


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