Oxygen/glucose deprivation increases the integration of recombinant P2X7 receptors into the plasma membrane of HEK293 cells

Milius, Doreen; Gröger-Arndt, Helke; Stanchev, Doychin; Lange-Dohna, Christine; Rößner, Steffen; Sperlágh, Beáta; Wirkner, Kerstin; Illéš, Peter

doi:10.1016/j.tox.2007.05.028

Cited by 21 publications

(11 citation statements)

References 32 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Importantly, not only is the level of its agonist relatively high at sites of tissue damage, there is also evidence that the activity of the P2X 7 receptor itself is increased under pathological conditions. This appears to reflect a broader tissue distribution (see above) and an increase in protein expression under the influence of inflammatory cytokines or bacterial products [68,69], and, perhaps more surprisingly, a decrease in activation threshold of the receptor in conditions of hypoxia [70][71][72]. Taken together, the data suggest that activation of P2X 7 in disease states is likely to occur more readily than might have been predicted from studies done under more conventional in vitro conditions.…”

Section: Renal Inflammation and Fibrosismentioning

confidence: 77%

P2 receptors in renal pathophysiology

Turner

Elliott

Tam

2009

Purinergic Signalling

View full text Add to dashboard Cite

Our knowledge and understanding of the P2 receptor signalling system in the kidney have increased significantly in the last ten years. The broad range of physiological roles proposed for this receptor system and the variety of P2 receptor subtypes found in the kidney suggest that any disturbance of function may contribute to several pathological processes. So far, most reports of a possible pathophysiological role for this system in the kidney have focussed on polycystic kidney disease, where abnormal P2 receptor signalling might be involved in cyst expansion and disease progression, and on the P2X 7 receptor, a unique P2X subtype, which when activated enhances inflammatory cytokine release and production, and also cell death. Expression of this particular receptor is upregulated in some forms of chronic renal injury and inflammatory diseases. Further studies of adenosine triphosphate signalling and P2 receptor expression in renal disorders could provide us with novel insights into the role of these receptors in both normal and abnormal kidney function.

show abstract

Section: Renal Inflammation and Fibrosismentioning

confidence: 77%

P2 receptors in renal pathophysiology

Turner

Elliott

Tam

2009

Purinergic Signalling

View full text Add to dashboard Cite

show abstract

“…More recently, Milius (2007) reported that OGD increases the integration of recombinant P2X 7 R into the plasma membrane of HEK293 cells. It is worthwhile exploring whether the combination of hypoxia and ischemia enhances the functional responsiveness of P2X 7 R or alters the trafficking properties of functional P2X 7 R accompanying the downregulation of its expression.…”

Section: Discussionmentioning

confidence: 99%

Downregulation of P2X₇ receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia

Wang

Cai

Chen

et al. 2008

Glia

View full text Add to dashboard Cite

Oligodendrocyte precursor cells (OPCs) are the predominant oligodendrocyte-lineage stage in the cerebral hemispheres of neonatal rat. Prior studies have shown that OPCs are highly vulnerable to hypoxic-ischemic injury, yet the mechanisms are not well understood. P2X 7 receptor (P2X 7 R) is an ATP-gated ion channel that has unusual properties and plays very complex roles in a variety of neuropathologic conditions. However, little is known about the involvement of P2X 7 R in OPCs development and injury. The present study was aimed at examining the presence of P2X 7 R in OPCs and evaluating the change of the receptor expression after hypoxia ischemia. Using Immunofluorescence, RT-PCR, and western blot analysis, we demonstrated that OPCs expressed P2X 7 R in vitro and in vivo. Activation of P2X 7 R in OPCs in response to 3 0 -O-(4-benzoyl) benzoyl-ATP (BzATP) led to an increased mobilization of intracellular calcium [Ca 21 ]i, formation of large pores and cell death. These functional responses were sensitive to pretreatment of cells with the P2X 7 R antagonist, Brilliant Blue G (BBG, 100 nM), which was a selective antagonist for P2X 7 R in nanomole range. A decrease in P2X 7 R expression was observed in cultured OPCs after exposure to oxygen-glucose deprivation (OGD) for 2 h in vitro. Using a neonatal hypoxic-ischemic injury model in postnatal 3 rats, the similar downregulation was also detected in ischemic cerebral cortex, subcortical white matter and hippocampus compared with sham operation controls. In conclusion, the present data demonstrated that OPCs expressed functional P2X 7 R. The post-ischemic downregulation of P2X 7 R suggested a role for this receptor in the pathophysiology of hypoxic-ischemic brain injury. V V C

show abstract

“…This IR was co-localised with astroglial and neuronal markers; immunoelectron microscopy revealed the expression of P2X 7 Rs on presynaptic elements of neurones and on glial cells. In order to clarify the mechanism of the ischaemic upregulation, HEK293 cells were transfected with the recombinant human P2X 7 R, the C-terminus of which was labelled with EGFP; the transfected cells were afterwards subjected to in vitro hypoxia/ischaemia [194]. The combined use of confocal laser scanning microscopy, flow cytometry and electrophysiology suggested that 12 h of in vitro ischaemia increased the integration of intracellularly localised P2X 7 Rs into the plasma membrane of HEK293 cells.…”

Section: Ischaemia/hypoxiamentioning

confidence: 99%

Pathophysiology of astroglial purinergic signalling

Franke

Verkhratsky

Burnstock

et al. 2012

Purinergic Signalling

Self Cite

174

139

View full text Add to dashboard Cite

Astrocytes are fundamental for central nervous system (CNS) physiology and are the fulcrum of neurological diseases. Astroglial cells control development of the nervous system, regulate synaptogenesis, maturation, maintenance and plasticity of synapses and are central for nervous system homeostasis. Astroglial reactions determine progression and outcome of many neuropathologies and are critical for regeneration and remodelling of neural circuits following trauma, stroke, ischaemia or neurodegenerative disorders. They secrete multiple neurotransmitters and neurohormones to communicate with neurones, microglia and the vascular walls of capillaries. Signalling through release of ATP is the most widespread mean of communication between astrocytes and other types of neural cells. ATP serves as a fast excitatory neurotransmitter and has pronounced long-term (trophic) roles in cell proliferation, growth, and development. During pathology, ATP is released from damaged cells and acts both as a cytotoxic factor and a proinflammatory mediator, being a universal "danger" signal. In this review, we summarise contemporary knowledge on the role of purinergic receptors (P2Rs) in a variety of diseases in relation to changes of astrocytic functions and nucleotide signalling. We have focussed on the role of the ionotropic P2X and metabotropic P2YRs working alone or in concert to modify the release of neurotransmitters, to activate signalling cascades and to change the expression levels of ion channels and protein kinases. All these effects are of great importance for the initiation, progression and maintenance of astrogliosis-the conserved and ubiquitous glial defensive reaction to CNS pathologies. We highlighted specific aspects of reactive astrogliosis, especially with respect to the involvement of the P2X 7 and P2Y 1 R subtypes. Reactive astrogliosis exerts both beneficial and detrimental effects in a context-specific manner determined by distinct molecular signalling cascades. Understanding the role of purinergic signalling in astrocytes is critical to identifying new therapeutic principles to treat acute and chronic neurological diseases.

show abstract

Oxygen/glucose deprivation increases the integration of recombinant P2X7 receptors into the plasma membrane of HEK293 cells

Cited by 21 publications

References 32 publications

P2 receptors in renal pathophysiology

P2 receptors in renal pathophysiology

Downregulation of P2X₇ receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia

Pathophysiology of astroglial purinergic signalling

Contact Info

Product

Resources

About

Oxygen/glucose deprivation increases the integration of recombinant P2X7 receptors into the plasma membrane of HEK293 cells

Cited by 21 publications

References 32 publications

P2 receptors in renal pathophysiology

P2 receptors in renal pathophysiology

Downregulation of P2X7 receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia

Pathophysiology of astroglial purinergic signalling

Contact Info

Product

Resources

About

Downregulation of P2X₇ receptor expression in rat oligodendrocyte precursor cells after hypoxia ischemia