title: 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, [Ca(2+)]i and level of CaSR expression were determined. The results showed that LPS increased cardiomyocytes apoptosis, [Ca(2+)]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, [Ca(2+)]i, and the expression of the CaSR protein. Conversely, pretreatment with NPS2390 decreased apoptosis of cardiomyocytes, MDA, LDH, TNF-α, IL-6 release, [Ca(2+)]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.
authors.affiliation: Department of Neonatology, The First Clinical Hospital of Harbin Medical University, Harbin, China.
authors.forename: Hong-yu
authors.initials: HY
authors.lastname: Wang
authors.forename: Xue-yan
authors.initials: XY
authors.lastname: Liu
authors.forename: Gan
authors.initials: G
authors.lastname: Han
authors.forename: Zhu-ying
authors.initials: ZY
authors.lastname: Wang
authors.forename: Xiao-xie
authors.initials: XX
authors.lastname: Li
authors.forename: Zhi-mei
authors.initials: ZM
authors.lastname: Jiang
authors.forename: Chun-ming
authors.initials: CM
authors.lastname: Jiang
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017209:Apoptosis; D020013:Calcium Signaling; D002478:Cells, Cultured; D005682:Gadolinium / Q000494:pharmacology; D015850:Interleukin-6 / Q000378:metabolism; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008315:Malondialdehyde / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000276:immunology* / Q000378:metabolism; D011810:Quinoxalines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044169:Receptors, Calcium-Sensing / Q000037:antagonists & inhibitors / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C569355:2-quinoxaline-carboxamide-N-adamantan-1-yl; D015850:Interleukin-6; D008070:Lipopolysaccharides; D011810:Quinoxalines; D044169:Receptors, Calcium-Sensing; D014409:Tumor Necrosis Factor-alpha; D008315:Malondialdehyde; D005682:Gadolinium; D007770:L-Lactate Dehydrogenase; D013482:Superoxide Dismutase; C038958:gadolinium chloride; D000218:Adamantane
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