Increased expression of phospholipase D1 in the brains of scrapie-infected mice.
Mitochondrial dysfunction and free radical-induced oxidative damage are critical factors in the pathogenesis of neurodegenerative diseases. Recently, phospholipid breakdown by phospholipase D (PLD) has been recognized as an important signalling pathway in the nervous system. Here, we examined the expression of PLD and alteration of membrane phospholipid in scrapie brain. We have found that protein expression and enzyme activity of PLD1 were increased in scrapie brains compared with controls; in particular, there was an increase in the mitochondrial fraction. PLD1 in mitochondrial membranes from scrapie brains, but not from control brains, was tyrosine phosphorylated. 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. Immunohistochemically, PLD1 immunoreactivity was significantly increased in activated astrocytes in both cerebral cortex and hippocampus of scrapie brains. Taken together, these results suggest that PLD activation might induce alterations in mitochondrial lipids and, in turn, mediate mitochondrial dysfunction in the brains of scrapie-infected mice.
Jin
Jae-Kwang
JK
Ilsong Institute of Life Science, Hallym University, Ilsong Building, Kwanyang-dong, 1605-4 Dongan-gu, Anyang, Kyonggi-do 431-060, Korea.
Kim
Nam-Ho
NH
Min
Do Sik
DS
Kim
Jae-Il
JI
Choi
Jin-Kyu
JK
Jeong
Byung-Hoon
BH
Choi
Seung-Il
SI
Choi
Eun-Kyoung
EK
Carp
Richard I
RI
Kim
Yong-Sun
YS
D000818:Animals; D001253:Astrocytes / Q000201:enzymology / Q000473:pathology; D001921:Brain / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D001923:Brain Chemistry; D002413:Cations, Divalent / Q000032:analysis; D007425:Intracellular Membranes / Q000737:chemistry / Q000201:enzymology; D015227:Lipid Peroxidation; D051379:Mice; D008810:Mice, Inbred C57BL; D008928:Mitochondria / Q000737:chemistry / Q000201:enzymology; D010712:Phosphatidic Acids / Q000032:analysis; D010739:Phospholipase D / Q000378:metabolism*; D010743:Phospholipids / Q000737:chemistry / Q000378:metabolism; D010766:Phosphorylation; D012608:Scrapie / Q000201:enzymology* / Q000473:pathology; D013347:Subcellular Fractions / Q000737:chemistry / Q000201:enzymology
D002413:Cations, Divalent; D010712:Phosphatidic Acids; D010743:Phospholipids; D010739:Phospholipase D; C106801:phospholipase D1