Phosphatidylinositol Transfer Protein Expression Altered by Aging and Parkinson Disease

Abstract

SUMMARY1. 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 PITPs 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 µM) of MPP + for 24 h at 37 • C. The level of PI-TP α and β and TH were determined using Western Blot analysis.3. Our data indicated that PI-TP α and β 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 α and β 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 α and β , 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 α and β in aged brain and in PD and suggest that oxidative stress may be responsible for the alteration of PI-TP.

Protective Effects of Resveratrol and Quercetin Against MPP+ -Induced Oxidative Stress Act by Modulating Markers of Apoptotic Death in Dopaminergic Neurons

“…In vitro, MPP ? administration induces a decline of TH in PC12 cells (Chalimoniuk et al 2006) and in other cellular models (Dalia et al 1996).…”

Proteomic Analysis of Mouse Brain Subjected to Spaceflight

“…Phosphatidylinositol transfer protein α (PITPNA) is involved with coordinating lipid metabolism and signaling [61], transferring phospholipids out of the endoplasmic reticulum and into other membranes [62]. Interestingly, an increase in oxidative stress has been shown to cause a decrease in this protein, particularly in the brains of aged or Parkinson’s disease models [63]. This lack has been associated with neurodegenerative disease, which has been linked to changes in glucose homeostasis [64].…”

The Role of Lipids in Parkinson’s Disease

“…Decreased levels of overall PI have been observed in the SN of male PD patients [270]. In rodents, MPTP decreases the expression level of striatal PI-transfer protein [309], which is involved in the transfer of PI across membranes [310].…”