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Study of PACAP and NGF signal transduction pathways in regulating serpin gene expression in PC12 cells
Abstract/OtherAbstract :
(Uncorrected OCR) Abstract of thesis entitled STUDY OF PACAP AND NGF SIGNAL TRANSDUCTION PATHWAYS IN REGULATING SERPIN GENE EXPRESSION IN PC12 CELLS Submitted by AU Yuen Kwan for the Degree of Master of Philosophy at The University of Hong Kong in August 2004 The rat pheochromocytoma PC12 cell is widely used as a model to study signaling mechanisms of pituitary adenylate cyclase-activating polypeptide (PACAP) and nerve growth factor (NGF) in regulating neurotrophic activities. PACAP is a 38-amino acid neuropeptide that belongs to the VIP/secretin/glucagon superfamily and NGF is one of the neurotrophins. When exposed to PACAP or NGF, PC12 cells change from a neoplastic cell type to a neuronal phenotype, with enhancement of neurite outgrowth and inhibition of proliferation. The serine proteinase inhibitor (serpins) superfamily plays important roles in many biological activities such as phagocytosis, blood coagulation, complement activation, fibrinolysis, programmed cell death and inflammation. In the present study, PACAP and NGF were found to activate the expression of a member of serpins, serpinb1b, in PC12 cells. The function of serpinb1b in PC12 cells is not clear. Both PACAP and NGF caused a significant increase in serpinb1b expression level within the first hour of treatment and the maximum effect being observed after 6 hours. The investigation of the involved transduction pathways revealed that the effect of PACAP and NGF on serpinb1b expression could be abolished in the presence of ascomycin (0.1 \xM) and U0126 (25 \xM). This indicates that this gene is regulated by the calcineurin and MEK1 pathways. In addition, co-treatment with PACAP and NGF resulted in an additive up-regulation of serpinb1b, suggesting that the two molecules could act synergistically. Besides serpinb1b expression, 2-day treatment of PACAP and NGF reduced the cell number and increased the cell size of PC 12 cell. The effect of PACAP in increasing cell size also required activation of the calcineurin and MEK1 pathways. The mutual pathways used in gene regulation and cell size regulation suggest the possible role of serpinb1b in PACAP-induced neurotrophic activities in PC 12 cells.
Authors :
Au, Yuen-kwan, 區箢筠
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Publication Detail :
Publisher :  University of Hong Kong (Pokfulam Road, Hong Kong)     Type :  Electronic Thesis & Dissertation     Format :  application/pdf, 122 leaves : ill. (some col.) ; 30 cm.    
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Subject :
Neuropeptides., Pituitary hormones., Adenylate cyclase., Peptide hormones., Nerve growth factor., Cellular signal transduction., Genetic regulation, Serpins., Cell lines., Pheochromocytoma
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unrestricted, The author retains all proprietary rights, (such as patent rights) and the right to use in future works.
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Languages :  eng    
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