Bcl-2 affects survival but not neuronal differentiation of PC12 cells

Past studies have shown that serum-free cultures of PC12 cells are a useful model system for studying the mechanisms of neuronal death after neurotrophic factor deprivation. These cultures, as well as NGF- deprived cultures of sympathetic neurons, manifest and endonuclease activity that leads to “apoptotic” internucleosomal DNA cleavage. Overexpression of the proto-oncogene bcl-2 blocks apoptotic death in various cell types. To study the actions of this protein in neuronal cells, we derived PC12 cell lines stably transfected with a cDNA encoding human bcl-2. It is reported here that lines expressing high levels of the exogenous bcl-2 protein are protected from both death and apoptotic DNA fragmentation caused by removal of trophic support. However, expression of high levels of exogenous bcl-2 neither mimics nor interferes with promotion of neurite outgrowth by NGF.

[1]  L. Greene,et al.  Internucleosomal DNA cleavage and neuronal cell survival/death , 1993, The Journal of cell biology.

[2]  J. Martinou,et al.  Prevention of programmed cell death of sympathetic neurons by the bcl-2 proto-oncogene. , 1992, Science.

[3]  E. Alnemri,et al.  Overexpressed full-length human BCL2 extends the survival of baculovirus-infected Sf9 insect cells. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[4]  R. Youle,et al.  Apoptosis and DNA degradation induced by 1-methyl-4-phenylpyridinium in neurons. , 1991, Biochemical and biophysical research communications.

[5]  John Calvin Reed,et al.  Differential expression of bcl2 protooncogene in neuroblastoma and other human tumor cell lines of neural origin. , 1991, Cancer research.

[6]  A. Tolkovsky,et al.  The Death Programme in Cultured Sympathetic Neurones Can Be Suppressed at the Posttranslational Level by Nerve Growth Factor, Cyclic AMP, and Depolarization , 1991, Journal of neurochemistry.

[7]  Suzanne Cory,et al.  bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship , 1991, Cell.

[8]  S. Korsmeyer,et al.  bcl-2 inhibits multiple forms of apoptosis but not negative selection in thymocytes , 1991, Cell.

[9]  L. Greene,et al.  Aurintricarboxylic acid rescues PC12 cells and sympathetic neurons from cell death caused by nerve growth factor deprivation: correlation with suppression of endonuclease activity , 1991, The Journal of cell biology.

[10]  L. Greene,et al.  Multiple agents rescue PC12 cells from serum-free cell death by translation- and transcription-independent mechanisms , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[11]  La Greene,et al.  Methodologies for the culture and experimental use of the PC12 rat pheochromocytoma cell line. , 1991 .

[12]  R. Schreiber,et al.  Bcl-2 is an inner mitochondrial membrane protein that blocks programmed cell death , 1990, Nature.

[13]  S. Korsmeyer,et al.  Deregulated Bcl-2 gene expression selectively prolongs survival of growth factor-deprived hemopoietic cell lines. , 1990, Journal of immunology.

[14]  R. Oppenheim,et al.  The neurotrophic theory and naturally occurring motoneuron death , 1989, Trends in Neurosciences.

[15]  Yves-Alain Barde,et al.  Trophic factors and neuronal survival , 1989, Neuron.

[16]  David L. Vaux,et al.  Bcl-2 gene promotes haemopoietic cell survival and cooperates with c-myc to immortalize pre-B cells , 1988, Nature.

[17]  P. Distefano,et al.  Inhibitors of protein synthesis and RNA synthesis prevent neuronal death caused by nerve growth factor deprivation , 1988, The Journal of cell biology.

[18]  M. Negrini,et al.  Molecular analysis of mbcl-2: Structure and expression of the murine gene homologous to the human gene involved in follicular lymphoma , 1987, Cell.

[19]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[20]  J. Sklar,et al.  Nucleotide sequence of a t(14;18) chromosomal breakpoint in follicular lymphoma and demonstration of a breakpoint-cluster region near a transcriptionally active locus on chromosome 18. , 1985, Proceedings of the National Academy of Sciences of the United States of America.

[21]  C. Croce,et al.  The t(14;18) chromosome translocations involved in B-cell neoplasms result from mistakes in VDJ joining. , 1985, Science.

[22]  C Sonnenschein,et al.  The role of estrogens on the proliferation of human breast tumor cells (MCF-7). , 1985, Journal of steroid biochemistry.

[23]  S. Korsmeyer,et al.  Cloning the chromosomal breakpoint of t(14;18) human lymphomas: clustering around Jh on chromosome 14 and near a transcriptional unit on 18 , 1985, Cell.

[24]  R. Oppenheim,et al.  Naturally Occurring Neuronal Death in Vertebrates , 1984 .

[25]  J. Sambrook,et al.  Molecular Cloning: A Laboratory Manual , 2001 .

[26]  L. Greene,et al.  Evidence for RNA synthesis-dependent and -independent pathways in stimulation of neurite outgrowth by nerve growth factor. , 1978, Proceedings of the National Academy of Sciences of the United States of America.

[27]  LA Greene,et al.  Nerve growth factor prevents the death and stimulates the neuronal differentiation of clonal PC12 pheochromocytoma cells in serum-free medium , 1978, The Journal of cell biology.

[28]  L. Greene,et al.  Establishment of a noradrenergic clonal line of rat adrenal pheochromocytoma cells which respond to nerve growth factor. , 1976, Proceedings of the National Academy of Sciences of the United States of America.