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• W2113487676 abstract "Abstract Communication between the SR (sarcoplasmic reticulum, SR) and mitochondria is important for cell survival and apoptosis. The SR supplies Ca 2+ directly to mitochondria via inositol 1,4,5-trisphosphate receptors (IP 3 Rs) 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 Ca 2+ signaling, causing apoptosis during H/Re. To investigate the above hypothesis, cultured cardiomyocytes were subjected to H/Re. We examined the distribution of IP 3 Rs in cardiomyocytes via immunofluorescence and Western blotting and found that type 3 IP 3 Rs were located in the SR. [Ca 2+ ]i, [Ca 2+ ] m and [Ca 2+ ] 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 [Ca 2+ ] SR , increased [Ca 2+ ] i and [Ca 2+ ] 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 induced the release of cytochrome c from mitochondria and the translocation of bak/bax to mitochondria. Taken together, these results reveal that CaR activation causes Ca 2+ release from the SR into the mitochondria through IP 3 Rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation." @default.
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• W2113487676 date "2010-06-17" @default.
• W2113487676 modified "2023-10-11" @default.
• W2113487676 title "Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation" @default.
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• W2113487676 doi "https://doi.org/10.1186/1423-0127-17-50" @default.
• W2113487676 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/2908572" @default.
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