tailieunhanh - Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation

Abstract Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP3Rs) at close contacts between the two organelles referred to as mitochondrion-associated ER membrane (MAM). Although it has been demonstrated that CaR (calcium sensing receptor) activation is involved in intracellular calcium overload during hypoxia/reoxygenation (H/Re), the role of CaR activation in the. | Lu et al. Journal of Biomedical Science 2010 17 50 http content 17 1 50 a NSC The cost of publication In Journal of Blomodlcal Science Is bome by the National Science Council Taiwan JOURNAL OF BIOMEDICAL SCIENCE RESEARCH Open Access Calcium-sensing receptors regulate cardiomyocyte Ca2 signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia reoxygenation Fang-hao Lu41 Zhiliang Tianf2 Wei-hua Zhang 1 5 Ya-jun Zhao1 Hu-lun Li3 Huan Ren4 Hui-shuang Zheng1 Chong Liu1 Guang-xia Hu1 Ye Tian1 Bao-feng Yang5 Rui Wang6 and Chang-qing Xu 1 5 Abstract Communication between the SR sarcoplasmic reticulum SR and mitochondria is important for cell survival and apoptosis. The SR supplies Ca2 directly to mitochondria via inositol 1 4 5-trisphosphate receptors IP3Rs at close contacts between the two organelles referred to as mitochondrion-associated ER membrane MAM . Although it has been demonstrated that CaR calcium sensing receptor activation is involved in intracellular calcium overload during hypoxia reoxygenation H Re the role of CaR activation in the cardiomyocyte apoptotic pathway remains unclear. We postulated that CaR activation plays a role in the regulation of SR-mitochondrial inter-organelle Ca2 signaling causing apoptosis during H Re. To investigate the above hypothesis cultured cardiomyocytes were subjected to H Re. We examined the distribution of IP3Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 I P3Rs were located in the SR. Ca2 i Ca2 m and Ca2 SR were determined using Fluo-4 x-rhod-1 and Fluo 5N respectively and the mitochondrial membrane potential was detected with JC-1 during reoxygenation using laser confocal microscopy. We found that activation of CaR reduced Ca2 SR increased Ca2 i and Ca2 m and decreased the mitochondrial membrane potential during reoxygenation. We found that the activation of CaR caused the cleavage of BAP31 thus generating the pro-apoptotic p20 fragment which .