LPS induces cardiomyocyte injury through calcium-sensing receptor

Abstract

Calcium-sensing receptor (CaSR) belongs to the family C of G-protein coupled receptors. We have previously demonstrated that CaSR could induce apoptosis of cultured neonatal rat ventricular cardiomyocytes in simulated ischemia/reperfusion. It remains unknown whether the CaSR has function in lipopolysaccharide (LPS)-induced myocardial injure. The aim of this study was to investigate whether the CaSR plays a role in LPS-induced myocardial injury. Cultured neonatal rat cardiomyocytes were treated with LPS, with or without pretreatment with the CaSR-specific agonist gadolinium chloride (GdCl3) or the CaSR-specific antagonist NPS2390. Release of TNF-α and IL-6 from cardiomyocytes was observed. Levels of malonaldehyde (MDA), lactate dehydrogenase (LDH), and activity of superoxide dismutase (SOD) were measured. In addition, apoptosis of the cardiomyocytes, [Ca2+]i and level of CaSR expression were determined. The results showed that LPS increased cardiomyocytes apoptosis, [Ca2+]i, MDA, LDH, TNF-α, IL-6 release, and CaSR protein expression. Compared with LPS treatment alone, pretreatment with GdCl3 further increased apoptosis of cardiomyocytes, MDA, LDH, TNF-α, IL-6 release, [Ca2+]i, and the expression of the CaSR protein. Conversely, pretreatment with NPS2390 decreased apoptosis of cardiomyocytes, MDA, LDH, TNF-α, IL-6 release, [Ca2+]i and the expression of the CaSR protein. These results demonstrate that LPS could induce cardiomyocyte injury. Moreover, LPS-induced cardiomyocyte injury was related to CaSR-mediated cardiomyocytes apoptosis, TNF-α, IL-6 release, and increase of intracellular calcium.

Differential gene expression analysis of symbiotic and aposymbiotic Exaiptasia anemones under immune challenge with Vibrio coralliilyticus

“…RIPK2 activates NF‐kappa‐β and induces cell death (McCarthy, Ni, & Dixit, ). Up‐regulation of CASR leads to apoptosis in rat myocytes exposed to LPS (Wang et al, ). To our knowledge, we are the first to report differential expression of RIPK2 and CASR in anthozoans.…”

Calcium Oxalate Induces Renal Injury through Calcium‐Sensing Receptor

“…Studies have demonstrated that injury to the rat myocardium induced by lipopolysaccharide is mediated by CaSR [15]. However, little is known about the role of CaSR in the formation of CaOx nephrolithiasis.…”

“…Wang et al [15] have reported that lipopolysaccharide-induced cardiomyocyte injury is related to CaSR-mediated OS and increases in the tumor necrosis factor- α (TNF- α ) and interleukin-6 (IL-6) levels. It remains unknown whether CaSR plays a role in CaOx-induced injury in cells and in animal models of urolithiasis.…”

Antiapoptotic and Antioxidant Effects of GSPE in Preventing Cyclosporine A-Induced Cardiotoxicity

“…These hypotheses list the formation of free oxygen radicals, lipid peroxidation, cytochrome P450 system induction, increase in intracellular calcium, increase in vasoconstrictor eicosanoid synthesis, and apoptosis. 1,[4][5][6] Free oxygen radical damage is the most frequently mentioned mechanism in the pathogenesis of CsAassociated organ toxicities. 1 Previously conducted studies have shown that it causes oxidative damage in the kidneys 1 and liver 7 and eventually an increase in lipid peroxidation.…”