Andrzej Małecki

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 animals 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 2xa0h intervals in a total dose of 40xa0mg/kg and then after 3, 7, and 14 days they were used for the investigation. PC12 cells were treated with increasing concentration (50–300xa0μM) of MPP+ for 24xa0h at 37°C. The level of PI-TPα and β and TH were determined using Western Blot analysis.3. Our data indicated that PI-TPα and β level decreased in brain of 36 months old rat by 20% comparing to the control value (4 months old). In animals model of PD, PI-TPα 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-TPα and β, TH expression, and viability of PC12 cells in a dose-dependent manner. H2O2, 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-TPα and β in aged brain and in PD and suggest that oxidative stress may be responsible for the alteration of PI-TP.

Neuroprotective effect of N-acetylcysteine in neurons exposed to arachidonic acid during simulated ischemia in vitro

The aim of the study was to assess neuroprotective effects of N-acetylcysteine (NAC; 100-200 microM) on cultured cortical neurons exposed to arachidonic acid (AA, 10 microM) during ischemia (oxygen-glucose deprivation). Ischemic conditions decreased neuron viability to 41-47% of normoxic controls; co-exposure with arachidonic acid further attenuated neuron viability to 36.73% after 24 h. Separate exposure to arachidonic acid in normoxia or to ischemic conditions only, increased the number of apoptotic nuclei to 33.56% or 36.78%, respectively. Combined exposure to arachidonic acid and ischemia increased apoptosis frequency to 62.20%. NAC (200 microM) decreased the number of apoptotic nuclei in normoxia in control and arachidonic acid exposed cells. NAC also decreased apoptosis frequency in ischemia to 14%. In neurons exposed to arachidonic acid and ischemic conditions, 100 and 200 microM NAC reduced apoptosis to 24.99% and 19.48%, respectively. NAC provided protection to neurons from toxicity due to arachidonic acid, ischemia and exposure to arachidonic acid in ischemic conditions.

Effects of N-acetylcysteine and ebselen on arachidonic acid release from astrocytes and neurons cultured in normoxic or simulated ischemic conditions

Arachidonic acid (AA) is released from cells after nervous tissue injuries.We treated rat cortical neurons and astrocytes cultured under normoxic or simulated ischemic conditions with N-acetylcysteine (100 or 200 microM) or ebselen (10 or 20 microM). N-acetylcysteine decreased AA release in normoxic astrocytes, while ebselen decreased AA release from astrocytes in both conditions. N-acetylcysteine produced no changes in neuronal AA release. A low dose of ebselen significantly increased AA release from neurons in both conditions. The influence of N-acetylcysteine and ebselen on AA release might be implicated in their effects on astrocytes and neurons, however, the exact mechanisms have yet to be explained.

The Relationship between Children's Blood Lead Level and Postural Stability

The Relationship between Childrens Blood Lead Level and Postural Stability Children, especially younger, are recognized as very susceptible to environmental lead exposure. In order to assess the effect of lead on spontaneous postural sway, we studied 327 children 4-13 years old, living in 4 cities in Upper Silesia an industrial region of Poland. Lead concentration in blood was measured by absorption atomic spectrometry (AAS) and posturography was performed using CATSYS 2000 - SWAY 7.0 equipment. Childrens postural sway characteristics decreased with age. Particular variables had higher values for boys than girls and were positively associated with blood lead levels. There was an association between postural sway characteristics and smoking habits of mother, usage of aminoglycosides and paracetamol. Posturography seems to be a useful tool for assessment of lead exposure effects on the nervous system at low blood lead levels.

Effects of Regular Recreational Exercise Training on Serum ANGPTL3-Like Protein and Lipid Profile in Young Healthy Adults

Abstract Evidence of the role of ANGPTL3, a liver-secreted glycoprotein, in serum lipid turnover, led us to hypothesize that this protein may be involved in modification of the lipid profile induced by exercise-training. Given the lack of data regarding this issue, the main goal of the present study was to investigate the effects of regular participation in a recreational physical activity program on serum ANGPTL3 and selected lipid profile measures in young, apparently healthy female and male adults. We compared serum ANGPTL3, lipid profile measures, common lipid ratios, the Atherogenic Index of Plasma (AIP) and glucose in fasting blood samples derived from 22 active physical education students including active females (AF, N=6) and males (AM, N=16) with samples from 28 relatively sedentary agematched peers, including female (SF, N=9) and male (SM, N=19) individuals not involved in any regular physical conditioning program. Despite high inter-individual variability of serum ANGPTL3, there was a general tendency toward higher serum ANGPTL3 and HDL-C in women compared to men, but without significant differences related to their physical activity status. Based on both routine lipid profile measures and lipid ratios, all participants had normal lipid profiles, normal glycemia, as well as favorable anthropometric indices not suggesting increased cardiometabolic risk. However, lower levels of the TG/HDL-C ratio and AIP in physically active compared to relatively sedentary participants, reflecting the predominance of large, buoyant LDL particles, strongly support the view of beneficial healthpromoting effects of regular participation in recreational sport activities.

Effects of olanzapine and paroxetine on phospholipase D activity in the rat brain

BACKGROUNDnPhospholipase D (PLD) plays a key role in a second messenger system producing phosphatidic acid, mediating, among others, serotonin 5-HT2 receptor activity. The aim of the study was to evaluate a possible effect of atypical antipsychotic drug, olanzapine (OLZ), and selective serotonin reuptake inhibitor (SSRI) antidepressant, paroxetine (PX), on oleate-activated PLD activity in plasma membranes isolated from rat brain cortex.nnnMETHODSnPLD activity was determined using a fluorometric assay. Ritanserin was used to determine the 5-HT receptor mode of action.nnnRESULTSnA single dose of 10 mmol/kg OLZ produced no change in rat brain cortex PLD activity, 20 mmol/kg OLZ caused a nonsignificant decrease, and long-term (21 days) administration of OLZ resulted in a 41.9% decrease in PLD activity. Single doses of PX significantly decreased PLD activity: 10 mmol/kg - by 28.6%; 20 mmol/kg - by 31.5%, and long-term (21 days) administration of PX - by 39.5%.nnnCONCLUSIONnThe study indicates that the 5-HT2 receptor-mediated inhibition of oleate-activated PLD may be a common part of the mechanisms of action of OLZ and PX.