title: Induction of Ca2+ signal mediated apoptosis and alteration of IP3R1 and SERCA1 expression levels by stress hormone in differentiating C2C12 myoblasts.
abstract: Glucocorticoid (GC) are stress hormones, whose cytotoxicity has been shown in various cells. The imbalance of calcium homeostasis is believed to be associated with the dexamethasone (DEX, a synthetic GC)-induced apoptosis. Here we show that in C2C12 myoblasts, DEX markedly up-regulated the expression of inositol 1,4,5-triphosphate receptor 1 (IP3R1) and down-regulated the expression of SERCA1 (sarcoendoplasmic reticulum Ca(2+)-ATPase 1), leading to calcium overload. Furthermore, the imbalance of calcium homeostasis increased the level of BAX, decreased the level of Bcl-2, induced cytochrome c release and activated caspase-3, leading to intranucleosomal DNA fragmentation and plasma membrane damage, eventually resulting in cell apoptosis. Taken together, by using C2C12 myoblasts as a model system, we demonstrated a novel mechanism for stress hormone-induced apoptosis: it is dependent on the induction of intracellular calcium overload via the alterations of IP3R1 and SERCA1 expressions.
authors.affiliation: Agricultural Ministry Key Laboratory of Swine Breeding and Genetics, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Chai
authors.forename: Qi
authors.initials: Q
authors.lastname: Xiong
authors.forename: Pengpeng
authors.initials: P
authors.lastname: Zhang
authors.forename: Rong
authors.initials: R
authors.lastname: Zheng
authors.forename: Jian
authors.initials: J
authors.lastname: Peng
authors.forename: Siwen
authors.initials: S
authors.lastname: Jiang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D002118:Calcium / Q000502:physiology*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D045304:Cytochromes c / Q000378:metabolism; D053938:DNA Fragmentation; D003907:Dexamethasone / Q000494:pharmacology; D015536:Down-Regulation / Q000187:drug effects; D005938:Glucocorticoids / Q000494:pharmacology*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000235:genetics*; D051379:Mice; D032446:Myoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000032:analysis / Q000235:genetics; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics*; D015398:Signal Transduction / Q000502:physiology; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000032:analysis / Q000235:genetics
chemical_list: C506944:Atp2a1 protein, mouse; D005938:Glucocorticoids; D053496:Inositol 1,4,5-Trisphosphate Receptors; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D003907:Dexamethasone; D045304:Cytochromes c; D053148:Caspase 3; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D002118:Calcium