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Calcium-sensing receptors regulate cardiomyocyte Ca2+ signaling via the sarcoplasmic reticulum-mitochondrion interface during hypoxia/reoxygenation
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نویسنده
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lu f.-h. ,tian z. ,zhang w.-h. ,zhao y.-j. ,li h.-l. ,ren h. ,zheng h.-s. ,liu c. ,hu g.-x. ,tian y. ,yang b.-f. ,wang r. ,xu c.-q.
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منبع
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journal of biomedical science - 2010 - دوره : 17 - شماره : 1
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چکیده
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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 (ip 3rs) 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 ip3rs were located in the sr. [ca2+]i,[ca2+]mand [ca2+] srwere 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+] iand [ca2+]mand 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 ca2+ release from the sr into the mitochondria through ip3rs and induces cardiomyocyte apoptosis during hypoxia/reoxygenation. © 2010 lu et al; licensee biomed central ltd.
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آدرس
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department of pathophysiology,harbin medical university,harbin 150086, China, department of pediatrics,hospital of harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086,china,bio-pharmaceutical key laboratory of heilongjiang province,harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086, China, department of neurobiology,harbin medical university,harbin 150086, China, department of immunology,harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086, China, department of pathophysiology,harbin medical university,harbin 150086, China, bio-pharmaceutical key laboratory of heilongjiang province,harbin medical university,harbin 150086, China, department of biology,lakehead university,thunder bay,on p7b5e1, Canada, department of pathophysiology,harbin medical university,harbin 150086,china,bio-pharmaceutical key laboratory of heilongjiang province,harbin medical university,harbin 150086, China
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Authors
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