Calcium overload is essential for the acceleration of staurosporine-induced cell death following neuronal differentiation in PC12 cells.
Differentiation of neuronal cells has been shown to accelerate stress-induced cell death, but the underlying mechanisms are not completely understood. Here, we find that early and sustained increase in cytosolic ([Ca2(+)]c) and mitochondrial Ca2(+) levels ([Ca2(+)]m) is essential for the increased sensitivity to staurosporine- induced cell death following neuronal differentiation in PC12 cells. Consistently, pretreatment of differentiated PC12 cells with the intracellular Ca2(+)-chelator EGTA-AM diminished staurosporine-induced PARP cleavage and cell death. Furthermore, Ca2(+) overload and enhanced vulnerability to staurosporine in differentiated cells were prevented by Bcl-XL overexpression. Our data reveal a new regulatory role for differentiation-dependent alteration of Ca2(+) signaling in cell death in response to staurosporine.
Seo
Su Ryeon
SR
Department of Molecular Bioscience, Kangwon National University, Chuncheon 200-701, Korea. suryeonseo@kangwon.ac.kr
Seo
Jeong Taeg
JT
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D053938:DNA Fragmentation; D008928:Mitochondria / Q000378:metabolism; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D016716:PC12 Cells / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D051381:Rats; D019311:Staurosporine / Q000494:pharmacology*; D051020:bcl-X Protein / Q000378:metabolism
C494813:Bcl2l1 protein, rat; D051020:bcl-X Protein; D053148:Caspase 3; D019311:Staurosporine; D002118:Calcium