Differential expression of metallothioneins in human prion diseases

We herein report an immunohistochemical and a Western blot analysis on meta l/free radical chelating proteins, metallothioneins (MTs; MT-I/II and MT-II I), in the brains of human prion disease patients with or without prion pro tein gene mutation and polymorphism. Irrespective of the isoforms of MTs, t he immunoreaction was detected in the cytoplasm and processes of the astroc ytes in the cerebral cortex and white matter in normal controls and prion d isease brains. Although the immunoreactivities for MTs in Creutzfeldt-Jakob disease (CJD) brains varied from case to case, they were generally depende nt upon the disease duration. In CJD patients with a relatively long diseas e course, the immunoreaction for both MT-I/II and MT-III in the astrocytes was significantly reduced, and this finding was not modified by the genotyp es of the patients. On the other hand, in patients with Gerstmann-Straussle r-Scheinker syndrome, MT-I/II immunoreactivity in the astrocytes was exclus ively reduced, while the immunoreaction for MT-III was relatively well pres erved. Especially the astrocytes in the vicinities of the kuru plaques exhi bited a weak or no immunoreaction even for MTs but a strong immunoreaction for glial fibrillary acidic protein. A quantitative Western blot analysis a lso revealed that MT-I/II protein accumulated in CJD brain with a short dis ease duration, whereas MT-III in CJD brain with a long disease duration was statistically significantly reduced in compa- rison to the normal brains. These findings suggest that the protein expression of MTs in the astrocytes is thus regulated differentially among human prion diseases and modified l ocally by such abnormal prion protein depositions as kuru plaques. Copyrigh t (C) 2000 S. Karger AG, Basel.