Premium
P3–261: Phospholipase D1 is up–regulated in the brain of patients with Alzheimer's disease and associated with amyloid precursor protein
Author(s) -
Kim Yong-Sun,
Jin Jae-Kwang,
Na Yeo-Jung,
Kim Nam-Ho,
Choi Eun-Kyoung,
Min Do Sik
Publication year - 2006
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2006.05.1530
Subject(s) - phospholipase d , phosphatidylethanolamine , phosphatidic acid , mitochondrion , amyloid precursor protein , pld2 , phospholipid , western blot , biology , phosphatidylcholine , biochemistry , phospholipase , microbiology and biotechnology , chemistry , alzheimer's disease , enzyme , medicine , membrane , disease , gene
Background: Mitochondrial dysfunction may play an important role in sporadic Alzheimer’s disease (AD) progression. Recently, we reported that amyloid precursor protein (APP) stimulates phospholipase D (PLD) activity in human astroglioma cells and the -amyloid region of APP is involved in the interaction with PLD1. Objective(s): To elucidate the involvement of PLD in the pathophysiology of AD, we examined the expression of PLD1 and alteration of membrane phospholipid in mitochondrial fraction from AD brains. Methods: To investigate whether protein expression and enzyme activity of PLD are altered in the brains of AD patients, we carried out Western blot and enzyme activity assay. Next, we investigated the levels of several phospholipids in mitochondrial membranes of control and AD brains using phospholipid analysis by TLC. Results: We have found that protein expression and enzyme activity of PLD1 were significantly increased in mitochondrial fraction of brains of AD patients compared with that in control brains. Furthermore, the concentration of mitochondrial phospholipids such as phosphatidylcholine and phosphatidylethanolamine was increased and the content of phosphatidic acid, a product of PLD activity, was up-regulated in the mitochondrial membrane fractions. Conclusions: These results suggest that APP may affect the composition of membrane phospholipids and/or stimulate the formation of lipid secondary messengers via PLD activation. The high level of PLD1 in the brain tissue of AD patients might provide a clue to the mechanism underlying the mitochondrial dysfunction associated with AD.