Corticotropin-releasing Hormone Induces Fas Ligand Production and Apoptosis in PC12 Cells via Activation of p38 Mitogen-activated Protein Kinase*

Recent experimental findings involve corticotropin-releasing hormone (CRH) in the cellular response to noxious stimuli and possibly apoptosis. The aim of the present work was to examine the effect of CRH on apoptosis and the Fas/Fas ligand system in an in vitro model, the PC12 rat pheochromocytoma cell line, which is widely used in the study of apoptosis and at the same time expresses the CRH/CRH receptor system. We have found the following. CRH induced Fas ligand production and apoptosis. These effects were mediated by the CRH type 1 receptor because its antagonist antalarmin blocked CRH-induced apoptosis and Fas ligand expression. CRH activated p38 mitogen-activated protein kinase, which was found to be essential for CRH-induced apoptosis and Fas ligand production. CRH also promoted a rapid and transient activation of ERK1/2, which, however, was not necessary for either CRH-induced apoptosis or Fas ligand production. Thus, CRH promotes PC12 apoptosis via the CRH type 1 receptor, which induces Fas ligand production via activation of p38.

[1]  T. Baram,et al.  Long-term, progressive hippocampal cell loss and dysfunction induced by early-life administration of corticotropin-releasing hormone reproduce the effects of early-life stress , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[2]  C. Culmsee,et al.  Corticotropin-Releasing Hormone Protects Neurons against Insults Relevant to the Pathogenesis of Alzheimer's Disease , 2001, Neurobiology of Disease.

[3]  A. Pavan,et al.  Prosaposin treatment induces PC12 entry in the S phase of the cell cycle and prevents apoptosis: activation of ERKs and sphingosine kinase , 2001, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[4]  K. Kolasa,et al.  Apoptotic protein expression and activation of caspases is changed following cholinergic denervation and hippocampal sympathetic ingrowth in rat hippocampus , 2000, Neuroscience.

[5]  R. Knight,et al.  Urocortin Protects against Ischemic and Reperfusion Injury via a MAPK-dependent Pathway* , 2000, The Journal of Biological Chemistry.

[6]  W. Scherbaum,et al.  Effects of a novel corticotropin-releasing-hormone receptor type I antagonist on human adrenal function , 2000, Molecular Psychiatry.

[7]  U. Felderhoff‐Mueser,et al.  Fas/CD95/APO‐1 Can Function as a Death Receptor for Neuronal Cells in Vitro and in Vivo and is Upregulated Following Cerebral Hypoxic‐Ischemic Injury to the Developing Rat Brain , 2000, Brain pathology.

[8]  L. Rubin,et al.  Role of Apoptosis Signal-Regulating Kinase in Regulation of the c-Jun N-Terminal Kinase Pathway and Apoptosis in Sympathetic Neurons , 2000, Molecular and Cellular Biology.

[9]  M. Kitamura,et al.  Dual potential of extracellular signal-regulated kinase for the control of cell survival. , 1999, Biochemical and biophysical research communications.

[10]  N. Neff,et al.  CEP‐1347 (KT7515), an Inhibitor of JNK Activation, Rescues Sympathetic Neurons and Neuronally Differentiated PC12 Cells from Death Evoked by three Distinct Insults , 1999, Journal of neurochemistry.

[11]  W. Vale,et al.  Corticotropin Releasing Factor Receptors and Their Ligand Family , 1999, Annals of the New York Academy of Sciences.

[12]  M. Wong,et al.  Chronic administration of the non-peptide CRH type 1 receptor antagonist antalarmin does not blunt hypothalamic-pituitary-adrenal axis responses to acute immobilization stress. , 1999, Life sciences.

[13]  C. Marshall,et al.  Nerve growth factor induces survival and differentiation through two distinct signaling cascades in PC12 cells , 1999, Oncogene.

[14]  D. Green,et al.  Withdrawal of Survival Factors Results in Activation of the JNK Pathway in Neuronal Cells Leading to Fas Ligand Induction and Cell Death , 1999, Molecular and Cellular Biology.

[15]  G. Borasio,et al.  Inhibitors of p38 mitogen‐activated protein kinase promote neuronal survival in vitro , 1998, Journal of neuroscience research.

[16]  R. Knight,et al.  Expression and protective effects of urocortin in cardiac myocytes , 1998, Neuropeptides.

[17]  P. Henslee-Downey,et al.  Energy level and sleep quality following bone marrow transplantation , 1997, Bone Marrow Transplantation.

[18]  R. Sapolsky,et al.  Astressin, a novel and potent CRF antagonist, is neuroprotective in the hippocampus when administered after a seizure , 1997, Brain Research.

[19]  S. Brooke,et al.  Endocrine Modulators of Necrotic Neuron Death , 1996, Brain pathology.

[20]  C. Ribak,et al.  Selective death of hippocampal CA3 pyramidal cells with mossy fiber afferents after CRH-induced status epilepticus in infant rats. , 1996, Brain research. Developmental brain research.

[21]  Michael E. Greenberg,et al.  Opposing Effects of ERK and JNK-p38 MAP Kinases on Apoptosis , 1995, Science.

[22]  G. Mazzocchi,et al.  Effect of Hypophysectomy on Corticotropin-Releasing Hormone and Adrenocorticotropin Immunoreactivities in the Rat Adrenal Gland , 1994, Molecular and Cellular Neuroscience.

[23]  G. Mazzocchi,et al.  Evidence that an extrahypothalamic pituitary corticotropin-releasing hormone (CRH)/adrenocorticotropin (ACTH) system controls adrenal growth and secretion in rats , 1993, Cell and Tissue Research.

[24]  E. Castanas,et al.  Protein Measurement of Particulate and Solubilized Ovine Liver Membranes , 1992, Annals of clinical biochemistry.

[25]  N. Yanaihara,et al.  Production of immunoreactive corticotropin-releasing hormone in various neuroendocrine tumors. , 1992, Japanese journal of clinical oncology.

[26]  Robert E. Anderson,et al.  Corticotropin releasing factor antagonist reduces ischemic hippocampal neuronal injury , 1991, Brain Research.

[27]  K. Yoshinaga,et al.  Immunoreactive corticotropin-releasing hormone, growth hormone-releasing hormone, somatostatin, and peptide histidine methionine are present in adrenal pheochromocytomas, but not in extra-adrenal pheochromocytoma. , 1990, The Journal of clinical endocrinology and metabolism.

[28]  H. Imura,et al.  Expression of adrenocorticotropin-releasing hormone precursor gene in placenta and other nonhypothalamic tissues in man. , 1988, Molecular endocrinology.

[29]  C. Jones,et al.  Secretion of corticotrophin releasing factor from the adrenal during splanchnic nerve stimulation in conscious calves. , 1988, The Journal of physiology.

[30]  N. Minamino,et al.  Biological and immunological characterization of corticotropin-releasing activity in the bovine adrenal medulla , 1988, Peptides.

[31]  D. Gann,et al.  Corticotropin‐releasing Factor in the Adrenal Medulla , 1987, Annals of the New York Academy of Sciences.

[32]  R. Hauger,et al.  Corticotropin‐releasing Factor Receptors: Distribution and Regulation in Brain, Pituitary, and Peripheral Tissues , 1987, Annals of the New York Academy of Sciences.

[33]  W. Nicholson,et al.  Pituitary and hypothalamic hormones in normal and neoplastic adrenal medullae: biologically active corticotropin-releasing hormone and corticotropin , 1987, Regulatory Peptides.

[34]  T. Suda,et al.  Characterization of immunoreactive corticotropin and corticotropin-releasing factor in human adrenal and ovarian tumours. , 1986, Acta endocrinologica.

[35]  G. Chrousos,et al.  Functional corticotropin releasing factor receptors in the primate peripheral sympathetic nervous system , 1986, Nature.

[36]  M. Niimi,et al.  Corticotropin-releasing factor (CRF)-like immunoreactivity in the adrenal medulla , 1984, Peptides.

[37]  U. K. Laemmli,et al.  Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4 , 1970, Nature.

[38]  A. Tischler,et al.  Nerve growth factor receptor signaling in proliferation of normal adult rat chromaffin cells , 1999, Cell and Tissue Research.

[39]  T. Baram,et al.  Corticotropin‐releasing hormone (CRH)‐containing neurons in the immature rat hippocampal formation: Light and electron microscopic features and colocalization with glutamate decarboxylase and parvalbumin , 1998, Hippocampus.

[40]  G. Nussdorfer,et al.  Comparison of ACTH and corticotropin-releasing hormone effects on rat adrenal steriodogenesis in vitro , 1991, Research in experimental medicine. Zeitschrift fur die gesamte experimentelle Medizin einschliesslich experimenteller Chirurgie.