P2X7 receptor-nitric oxide interaction mediates apoptosis in mouse immortalized mesangial cells exposed to high glucose
Open Access
- 1 June 2022
- journal article
- research article
- Published by FapUNIFESP (SciELO) in Brazilian Journal of Nephrology
- Vol. 44 (2), 147-154
- https://doi.org/10.1590/2175-8239-jbn-2021-0086
Abstract
Introduction: Diabetes mellitus (DM) is a chronic disease characterized by hyperglycemia that leads to diabetic nephropathy (DN). We showed that P2X(7), a purinergic receptor, was highly expressed in DM; however, when oxidative stress was controlled, renal NO recovered, and the activation of this receptor remained significantly reduced. The aim of this study was to assess the influence of NO on the P2X(7) and apoptosis in mouse immortalized mesangial cells (MiMC) cultured in high glucose (HG) medium. Methods: MiMCs were cultured with DMEM and exposed to normal glucose (NG), mannitol (MA), or HG. Cell viability was assessed by an automated counter. Supernatants were collected for NO quantification, and proteins were extracted for analysis of NO synthases (iNOS and eNOS), caspase-3, and P2X(7). Results: Cell viability remained above 90% in all groups. There was a significant increase in the proliferation of cells in HG compared to MA and NG. NO, iNOS, caspase-3, and P2X(7) were significantly increased in HG compared to NG and MA, with no changes in eNOS. We observed that there was a strong and significant correlation between P2X(7) and NO. Discussion: The main finding was that the production of NO by iNOS was positively correlated with the increase of P2X(7) in MCs under HG conditions, showing that there is a common stimulus between them and that NO interacts with the P2X(7) pathway, contributing to apoptosis in experimental DM. These findings could be relevant to studies of therapeutic targets for the prevention and/or treatment of hyperglycemia-induced kidney damage to delay DN progression.Keywords
This publication has 46 references indexed in Scilit:
- In vitro silencing of the insulin receptor attenuates cellular accumulation of fibronectin in renal mesangial cellsCell Communication and Signaling, 2012
- PI3K, Rho, and ROCK play a key role in hypoxia-induced ATP release and ATP-stimulated angiogenic responses in pulmonary artery vasa vasorum endothelial cellsAmerican Journal of Physiology-Lung Cellular and Molecular Physiology, 2009
- Cell signaling via the P2X7 nucleotide receptor: linkage to ROS production, gene transcription, and receptor traffickingPurinergic Signalling, 2009
- The role of the purinergic P2X7 receptor in inflammationJournal of Inflammation, 2007
- Purinergic signalling in the immune system. A brief updatePurinergic Signalling, 2007
- Lack of Endothelial Nitric-Oxide Synthase Leads to Progressive Focal Renal InjuryThe American Journal of Pathology, 2007
- A role for P2X7 in microglial proliferationJournal of Neurochemistry, 2006
- Glomerular expression of the ATP-sensitive P2X7 receptor in diabetic and hypertensive rat modelsKidney International, 2004
- Changes in intracellular calcium concentration and P2X1 receptor expression in hypertrophic rat urinary bladder smooth muscleNeurourology and Urodynamics, 2004
- Trypan Blue Exclusion Test of Cell ViabilityCurrent Protocols in Immunology, 1997