Neuropharmacology. 2024 Mar 1:245:109818.doi: 10.1016/j.neuropharm.2023.109818. Epub 2023 Dec 22.

本文采用的英格恩产品: DNA-Entranster-invivo

P2Y13 receptor involved in HIV-1 gp120 induced neuropathy in superior cervical ganglia through NLRP3 inflammasome activation

Affiliations

Affiliations

  • 1 Department of Physiology, School of Basic medicine, Jiangxi Medical College, Nanchang University, China; Jinan Center for Disease Control and Prevention, Jinan, China.
  • 2 Department of Physiology, School of Basic medicine, Jiangxi Medical College, Nanchang University, China.
  • 3 Department of Basic medicine, School of Basic medicine, Jiangxi Medical College, Nanchang University, China.
  • 4 Department of Clinical Medicine, School of Marry Queen, Jiangxi Medical College, Nanchang University, China.
  • 5 Center of Hematology, the 1st affiliated Hospital, Jiangxi Medical College, Nanchang University, China; Institute of Hematology, Academy of Clinical Medicine of Jiangxi Province, Nanchang, China.
  • 6 Department of Physiology, School of Basic medicine, Jiangxi Medical College, Nanchang University, China. Electronic address: liusm@ncu.edu.cn.

Abstract

Cardiac autonomic neuropathy resulting from human immunodeficiency virus (HIV) infection is common; however, its mechanism remains unknown. The current work attempted to explore the function and mechanism of the P2Y13 receptor in HIV-glycoprotein 120 (gp120)-induced neuropathy in cervical sympathetic ganglion. The superior cervical ganglion (SCG) of the male SD rat was coated with HIV-gp120 to establish a model of autonomic neuropathy. In each group, we measured heart rate, blood pressure, heart rate variability, sympathetic nerve discharge and cardiac function. The expression of P2Y13 mRNA and protein in the SCG was tested by real-time polymerase chain reaction and western blotting. Additionally, this study focused on identifying the protein levels of NOD-like receptor family pyrin domain-containing 3 (NLRP3), Caspase-1, Gasdermin D (GSDMD), interleukin (IL)-1β and IL-18 in the SCG using western blotting and immunofluorescence. In gp120 rats, increased blood pressure, heart rate, cardiac sympathetic nerve activity, P2Y13 receptor levels and decreased cardiac function could be found. P2Y13 shRNA or MRS2211 inhibited the above mentioned changes induced by gp120, suggesting that the P2Y13 receptor may be engaged in gp120-induced sympathetic nerve injury. Moreover, the levels of NLRP3, Caspase-1, GSDMD, IL-1β and IL-18 in the gp120 group were increased, while significantly decreased by P2Y13 shRNA or MRS2211. Therefore, the P2Y13 receptor is involved in gp120-induced sympathetic neuropathy, and its molecular mechanism shows an association with the activation of the NLRP3 inflammasome, followed by GSDMD formation along with the release of inflammatory factors including IL-1β and IL-18. This article is part of the Special Issue on “Purinergic Signaling: 50 years”.

Keywords: Autonomic neuropathy; HIV-1 envelope glycoprotein gp120; NLRP3; P2Y(13) receptor; Pyroptosis; Superior cervical ganglion.

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