TY - JOUR
T1 - Bone morphogenetic proteins induce apoptosis and growth factor dependence of cultured sympathoadrenal progenitor cells
AU - Song, Qingbin
AU - Mehler, Mark F.
AU - Kessler, John A.
N1 - Funding Information:
This study was supported by an Irma T. Hirschl Career Scientist Award (M.F.M.) and grants from the Muscular Dystrophy Association (M.F.M.) and the National Institutes of Health, NS35320 (M.F.M.) and NS20013 and NS20778 (J.A.K.). We thank Antoinette Barnecott for her help in the preparation of the manuscript.
PY - 1998/4/1
Y1 - 1998/4/1
N2 - Neuron numbers in developing vertebrate organisms are regulated by the availability of growth factors which promote their survival. However, neuron survival may also be regulated by growth factors which promote rather than prevent cell death. This study examined the effects of bone morphogenetic proteins (BMPs) in inducing apoptosis of MAH cells, an immortalized sympathoadrenal progenitor cell line. Treatment of MAH cells with BMP2 or BMP4 killed the cells in a dose-dependent manner. By contrast, treatment with BMP7 or TGFβ1 failed to affect survival, suggesting that induction of apoptosis is specific to the dpp subgroup of BMPs. Survival after treatment with BMP2 or BMP4 required addition of fibroblast growth factor (FGF) and nerve growth factor (NGF), indicating that BMP treatment made the neurons dependent upon an exogenous factor for survival. Several experimental observations suggested an apoptotic mechanism for BMP-induced death. After BMP2 treatment, the cells progressively shrank and became pyknotic. Further, there was prominent endonucleosomic cleavage of DNA (laddering) as well as TUNEL staining. Moreover, BMP-induced death was inhibited by the caspase inhibitor z-VAD and was partially prevented by the endonuclease inhibitor aurintricarboxylic acid. These observations suggest that neuron numbers may be regulated by factors which promote death and that exposure to such factors may be a signal for the development of dependence upon other growth factors for survival.
AB - Neuron numbers in developing vertebrate organisms are regulated by the availability of growth factors which promote their survival. However, neuron survival may also be regulated by growth factors which promote rather than prevent cell death. This study examined the effects of bone morphogenetic proteins (BMPs) in inducing apoptosis of MAH cells, an immortalized sympathoadrenal progenitor cell line. Treatment of MAH cells with BMP2 or BMP4 killed the cells in a dose-dependent manner. By contrast, treatment with BMP7 or TGFβ1 failed to affect survival, suggesting that induction of apoptosis is specific to the dpp subgroup of BMPs. Survival after treatment with BMP2 or BMP4 required addition of fibroblast growth factor (FGF) and nerve growth factor (NGF), indicating that BMP treatment made the neurons dependent upon an exogenous factor for survival. Several experimental observations suggested an apoptotic mechanism for BMP-induced death. After BMP2 treatment, the cells progressively shrank and became pyknotic. Further, there was prominent endonucleosomic cleavage of DNA (laddering) as well as TUNEL staining. Moreover, BMP-induced death was inhibited by the caspase inhibitor z-VAD and was partially prevented by the endonuclease inhibitor aurintricarboxylic acid. These observations suggest that neuron numbers may be regulated by factors which promote death and that exposure to such factors may be a signal for the development of dependence upon other growth factors for survival.
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U2 - 10.1006/dbio.1998.8847
DO - 10.1006/dbio.1998.8847
M3 - Article
C2 - 9527885
AN - SCOPUS:0032053853
SN - 0012-1606
VL - 196
SP - 119
EP - 127
JO - Developmental Biology
JF - Developmental Biology
IS - 1
ER -