Clusterin is widely up-regulated in many tissues in association with various patho-physiological conditions, its upregulation being implicated in various biological processes such as cell proliferation, differentiation, and apoptotic cell death. However, it remains to be further elucidated about how clusterin could exert its function in those opposing processes, since proliferation, differentiation and apoptosis are contradictory in cellular events. Clusterin is known to bind to many molecules including heparin, beta-amyloid, prion peptide, paraoxnase, immunoglobulin, complement components, and lipids. The binding ability of clusterin to other molecules and its involvement in various biological processes led us to hypothesize that its function might be modulated by interacting with specific effecter molecules which are involved in opposing cellular events. Thus, in this dissertation, we investigated the regulation of clusterin and its interacting molecules involved in the proliferation of primary astrocytes as well as in the neuronal differentiation of PC12 cells.
Clusterin expression is increased in the reactive astrocytes following experimental brain injuries as well as in disease states such as inflammation and neurodegeneration, although its function has not been clearly elucidated. Thus, whether or not clusterin could have any effect on proliferation of reactive astrocytes was examined. Primary astorcytes transfected with clusterin cDNA (pcDNA3-CLU) highly expressed clusterin, while the basal low level of clusterin was detected in the cells transfected with the control plasmid (pcDNA3). Transient clusterin over-expression enhanced incorporation of 3[H]-thymidine into DNA synthesis of primary astrocytes by 50 % compared to the control vector transfected cells at 24 hours after transfection of clusterin cDNA. Proliferation property of clusterin in astrocytes was further confirmed by PCNA immunostaining and western blot analysis. Its proliferation activity is cert