PHOSPHOLIPASE-C ISOZYMES IN THE HUMAN BRAIN AND THEIR CHANGES IN ALZHEIMERS-DISEASE

Phosphoinositide-specific phospholipase C is a key enzyme in signal tr ansduction. We have previously demonstrated that an isozyme of phospho lipase C, phospholipase C-delta 1, accumulates aberrantly in the brain s of patients with Alzheimer's disease. In the present study, we exami ned the property of phospholipase C isozymes in human brains using the methods of chromatofocusing and gel filtration chromatography, and in vestigated their changes in Alzheimer's disease brains. The chromatofo cusing profile of human brain phospholipase C activity on a Mono P HR column demonstrated that phospholipase C-gamma 1, exhibiting an isoele ctric point value of 5.2, and phospholipase C-delta 1, exhibiting isoe lectric point values of 5.2 and 4.6, are partly overlapped in their el ution. In contrast, the elution profiles of control and Alzheimer's di sease brain phospholipase C on Superdex 200 pg column gel filtration c hromatography indicated that phospholipase C-gamma 1 and phospholipase C-delta 1 can be separated with the elution position having a molecul ar weight of about 240,000 and 140,000, respectively, in the human bra in. Using this gel filtration chromatography it was revealed that the phospholipase C-gamma 1 activity was significantly decreased and the p hospholipase C-delta 1 activity was significantly increased in Alzheim er's disease brains compared with controls. These results suggest that the phospholipase C isozymes are differentially involved in Alzheimer 's disease. (C) 1997 IBRO. Published by Elsevier Science Ltd.