NR AXQQ
AU Kuznecovs,I.
TI Polyprenol could Improve Disbalance in Membrane Protein Glycosylation in Prion Infection
QU International Conference - Prion 2007 (26.-28.9.2007) Edinburgh International Conference Centre, Edinburgh, Scotland, UK - Book of Abstracts: Pathology and Pathogenesis P03.101
IA http://www.prion2007.com/pdf/Prion Book of Abstracts.pdf
PT Konferenz-Poster
AB
Introduction: Dolichyl Phosphate Cycle (DPC) is one of the possible targets in prion infection. The aim of this study IS to investigate the contributing mechanism of DPC substitute - poliprenol (PP) in this process.
Methods: Dolichol (Dol) and Dolichvl Phosphate (Dol-P) contents in brain homogenates,blood and urine were assayed by HPLC in mouse brain infected with scarpie. The intensity of the glycoprotein synthesis in subcellular fractions was estimated based on the number of Dol-P[14C]Mannose Starting Glycosylation Complexes (SGC). In an effort to produce an affect on the DPC regulation the animals were intranasally administered [1-3H]Polyprenol (PP), a substance, which is believed to be a predecessor of endogenic Dol-P.
Results: In the early period of disease the neurons therewith cumulate nonglycosylated proteins, morphologically reflected by the cellular hypertrophy. The pathologic process was shown to result in the fall of Dol-P in neurons by 20-25%. Dol increased in serum and later in urine. Intranasal PP application decreased Dol content in serum and brain. Application was beneficial for revealing 17,8% of PP activity in brain, 8,3% in the form of Dol-P. It is well established that the number of SGC in the mitochondria is 10-12 times as high as that in the Golgi apparatus. After PP application this gap attains 1,7-2,5 in favour of the Golgi without Dol-P drop in brain.
Discussion: The fact is that in prion infection the resistance of membranes in cerebral neurons is ensured by a sufficient level of the glycoprotein synthesis running through DPC in mitochondria. However in prion infection the mitochondria have to ensure a higher energy consumption of the cells. The subcellular redistribution of the glycosilation sites under extreme conditions for brain is believed to be as a marker of resistance to prion infection According to the obtained information the PP provide a prodrug which makes up for a disbalance in membrane protein glycosylation in prion infection.
AD I. Kuznecovs, Preventive medicine research society, Molecular pathology Unit, Latvia
SP englisch
PO Schottland