Bioenergetikai változások glutamát excitotoxicitásban és oxidatív stresszben = Bioenergetical changes in glutamate excitotoxicity and oxidative stress
2006
Munkank egyfelől az ischemia es szamos neurodegenerativ betegseg pathomechanizmusaban meghatarozo szerepet jatszo oxidativ stressz akut hatasaival, masfelől az oxidativ stressz keletkezesevel kapcsolatban hozott uj eredmenyeket. Megallapitasok: 1) Enyhe oxidativ stressz potencirozza a Na-terhelesre bekovetkező glutamat felszabadulast es csokkenti a gluthation mennyiseget izolalt idegvegződesekben. 2) Az oxidativ stressz gatolja a pH regulaciot es a mitokondriumok kalcium haztartast regulalo szerepet az agy-ver gatat alkoto kapillarisokbol tenyesztett endothel sejtekben. 3) A mitokondrialis legzesi lanc komponensei kozul a ROS keletkezeseben a meghatarozo a komplex I gatlasa, amely mar kis mertekű gatlas eseten olyan mennyisegű ROS kepzessel jar, hogy gatolja az endogen akonitazt. 4) A legesi lanc mellett fontos altalunk leirt uj forrasa a ROS keletkezesnek az alpha-ketoglutarat enzim, amely normal katalitikus műkodese soran szuperoxidot es hidrogen peroxidot termel, amit a NADH/NAD arany regulal. 5) Agykeregből szarmazo sejttenyeszeten a glutamat excitotoxikus hatasaban szerepet jatszanak a transient receptor potential csatornak es a pathomechanizmus fontos resze a sejtek NADH szintjenek csokkenese. 6) Megtortent az eddig ismeretlen funkcioju kalcium-aktivalta nem-szelektiv kation csatornak reszletes jellemzese agyi kapillaris endothel sejt tenyeszetben. | The findings of this research project show, on one hand, sensitive processes that are impaired by oxidative stress in neurons and rat brain capillary endothelial cells (RBCE), on the other hand, mechanisms involved in the generation of oxidative stress. Major findings: i) Hydrogen peroxide potentiate the release of glutamate induced by a sodium load in isolated nerve terminals. ii) Oxidative stress impairs the intracellular pH regulation and the mitochondrial calcium regulation in RBCE cells. iii) Physiologically the most relevant site of reactive oxygen species (ROS) production in the respiratory chain is at complex I; when this complex is inhibited by 25-30 %, relevant to Parkinson?s disease, ROS is generated in sufficient amount to inhibit endogenous mitochondrial aconitase. iv) In addition to the respiratory chain, alpha-ketoglutarate dehydrogenase could be a significant source of ROS generation in mitochondria under conditions when the NADH/NAD ratio is increased (ischemia, Parkinson?s disease). v) Transient receptor potential (TRP) channels are involved in the delayed calcium deregulation (DCD) associated with glutamate excitotoxicity in cortical cell cultures. DCD is accompanied by a significant drop in the intracellular NADH level. vi) Calcium-activated non-selective cation channels, which are abundant in RBCE cells, have been characterized; the gating characteristics as well as the regulation by nucleotides have been described in details.
Keywords:
- Correction
- Source
- Cite
- Save
- Machine Reading By IdeaReader
0
References
0
Citations
NaN
KQI