Phosphatidylinositol transfer protein expression altered by aging and Parkinson disease.
1. Phosphatidylinositol transfer proteins (PI-TP) are responsible for the transport of phosphatidylinositol (PI) and other phospholipids from endoplasmic reticulum to the other membranes and indirectly for lipid mediated signaling. Till now little is known about PI-TPs in brain aging and neurodegeneration. The aim of this study was to investigate expression of PI-TP in the brain during aging and in animal's model of Parkinson disease (PD) induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Moreover, in vitro, effect of 1-methyl-4-phenyl-pyridine cation (MPP(+)) on PI-TP, tyrosine hydroxylase (TH) protein level, and viability of cells was investigated. 2. Wistar rats 4, 24, and 36 months old and C57/BL mice and rat pheochromocytoma (PC12) cell line were used for the studies. Mice C57/BL received three injections of MPTP in saline at 2 h intervals in a total dose of 40 mg/kg and then after 3, 7, and 14 days they were used for the investigation. PC12 cells were treated with increasing concentration (50-300 microM) of MPP(+) for 24 h at 37 degrees C. The level of PI-TP(alpha and beta) and TH were determined using Western Blot analysis. 3. Our data indicated that PI-TP(alpha and beta) level decreased in brain of 36 months old rat by 20% comparing to the control value (4 months old). In animal's model of PD, PI-TP(alpha and beta) level was significantly lower by 85, 69, 64% in striatum at 3, 7, and 14 days after MPTP injection, respectively, compared to the control value. MPP(+) decreased PI-TP(alpha and beta), TH expression, and viability of PC12 cells in a dose-dependent manner. H(2)O(2), menadione, and NO donor significantly decreased the PI-TP level and viability of PC12 cells. 4. Our results indicate the lower protein expression of PI-TP(alpha and beta) in aged brain and in PD and suggest that oxidative stress may be responsible for the alteration of PI-TP.
Chalimoniuk
Małgorzata
M
Medical Research Center, Department of Cellular Signaling, Polish Academy of Sciences, 5 Pawińskiego St., 02-106, Warsaw, Poland. mchalim@yahoo.com
Snoek
Gerry T
GT
Adamczyk
Agata
A
Małecki
Andrzej
A
Strosznajder
Joanna B
JB
D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D000375:Aging / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002470:Cell Survival / Q000187:drug effects; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D016716:PC12 Cells; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism*; D049294:Phospholipid Transfer Proteins / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D049294:Phospholipid Transfer Proteins; C493469:Pitpna protein, rat; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine