P2RX7 [Neurosurgery Wiki]

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====== P2RX7 ======

P2X purinoceptor 7 is a protein that in humans is encoded by the P2RX7 gene. The product of this gene belongs to the family of [[Purinergic receptor]]s for [[ATP]]. Multiple alternatively spliced variants which would encode different isoforms have been identified although some fit nonsense-mediated decay criteria.

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The activation of P2RX7 plays an important role in [[endotheliocyte]] damage and [[Blood-Brain Barrier disruption]]. [[Ferroptosis]] is a novel pattern of [[programmed cell death]] caused by the accumulation of intracellular [[iron]] and [[lipid peroxidation]], resulting in [[ROS]] production and [[cell death]]. 
Liu et al. explored the mechanism of P2RX7 in reducing hemorrhagic transformation pathogenesis after [[acute ischemic stroke]] by regulating endotheliocyte ferroptosis. Male SD rats were performed to establish [[middle cerebral artery occlusion]] (MCAO) model injected with 50% high [[glucose]] (HG) and HUVECs were subjected to OGD/R treated with high glucose (30 mM) for establishing HT model in vivo and in vitro. P2RX7 inhibitor (BBG), and P2RX7 small interfering [[RNA]]s (siRNA) were used to investigate the role of P2RX7 in BBB after MCAO in vivo and OGD/R in vitro, respectively. The [[neurological deficit]]s, [[infarct]] volume, degree of [[intracranial hemorrhage]], the integrity of the BBB, [[immunoblotting]], and [[immunofluorescence]] were evaluated at 24 h after MCAO. 
The study found that the level of P2RX7 was gradually increased after MCAO and/or treated with HG. The results showed that treatment with HG after MCAO can aggravate neurological deficits, infarct volume, oxidative stress, iron accumulation, BBB injury in the HT model, and HG-induced HUVECs damage. The inhibition of P2RX7 reversed the damaging effect of HG, significantly downregulated the expression level of [[P53]], HO-1, and p-ERK1/2, and upregulated the level of SLC7A11 and GPX4, which implicated that P2RX7 inhibition could attenuate oxidative stress and ferroptosis of the [[endothelium]] in vivo and in vitro. The data provided [[evidence]] that the P2RX7 plays an important role in HG-associated [[oxidative stress]], endothelial damage, and BBB disruption, which regulates HG-induced HT by [[ERK1]]/2 and [[P53]] signaling pathways after MCAO
((Liu C, Tian Q, Wang J, He P, Han S, Guo Y, Yang C, Wang G, Wei H, Li M. Blocking [[P2RX7]] Attenuates Ferroptosis in Endothelium and Reduces HG-induced Hemorrhagic Transformation After MCAO by Inhibiting ERK1/2 and P53 Signaling Pathways. Mol Neurobiol. 2022 Oct 25. doi: 10.1007/s12035-022-03092-y. Epub ahead of print. Erratum in: Mol Neurobiol. 2022 Nov 23;: PMID: 36282438.)).