Analysis of Factors To Control The Conversion Of Abnormal Prion Protein From Normal Prion Protein

2003 Fiscal Year Final Research Report Summary

• Project/Area Number: 14570192
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Nagasaki University
• Principal Investigator: SHIGEMATU Kazuto Nagasaki University, Graduate School of Biomedical Medicine, Department of Pathology, Assistant Professor, 大学院・医歯薬学総合研究科, 助教授 (20154205)
• Project Period (FY): 2002 – 2003
• Keywords: PrP / protease-resistant / Kidney / cDNA subtraction / NADH oxidase / ROS / osteopontin

Research Abstract

There is no correlation between the expression level of PrP mRNA and the accumulation of protease-resitant isoform of Prion protein (PrPSc), suggesting the presence of factors which control the conversion to PrPSc from the normal PrP. Among of them, the kidney was selected as a target organ, because of highly expression of PrP mRNA. The evidence that PrPSc was accumulating in a kidney through an experiment could not obtained, although there is low infectivity at only 18 weeks after inoculation. Microscopically, the expansion of glomerulus in the Prion-infected kidney was found and the immunofluorescent study showed the deposits. of Ig A, Ig M, C1q, C3 and fibronectin. The cDNA subtraction demonstrated the high expression of NADH oxidase (NOX), mitochondrial respiratory enzyme and osteopontin/Eta-1 in the infected kidney, while low expression of kidney androgen regulated protein and ornithine decarboxylase. These results indicated the possibility that the infected kidney becomes more sensitive to (reactive oxygen species (ROS) injury, leading to a progressive oxidative disruption. Taken together with the reports that a tumor-asociated cell surface NADH oxidase (tNOX) exhibits characteristics to product protelnase K resistant particle and that the cate chin, extracts from green tea, inhibits the effect of tNOX, the possibility that the antioxidant agents may inhibit the conversion to PrPSc from normal form would have to considered. Indeed, we could demonstrate that epigallocatechin gallate, exracts from green tea, has the inhibitory effect in vitro. Osteopontin mRNA was highly expressed in the microglia of the infected brain as well as kidney, but not, in the macrophage of spleen showing the high infectivity. This phenomenon may help us to resolve the pathogenesis of prion disease.