Induction of Ca2+ signal mediated apoptosis and alteration of IP3R1 and SERCA1 expression levels by stress hormone in differentiating C2C12 myoblasts.
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.
Chai
Jin
J
Agricultural Ministry Key Laboratory of Swine Breeding and Genetics, College of Animal Science and Technology, Huazhong Agricultural University, Wuhan 430070, China.
Xiong
Qi
Q
Zhang
Pengpeng
P
Zheng
Rong
R
Peng
Jian
J
Jiang
Siwen
S
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
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