Transition metal ions significantly decrease phospholipase C activity degrading phosphatidylinositol-4,5-bisphosphate in the brain cortex.
Highly reactive transition metals, such as copper and iron play an obligatory role in generating of reactive oxygen species (ROS). Many neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD) show increased accumulation of these metals. Phosphoinositide metabolism is altered in neurodegenerative diseases. In the present study, we examined the effect of CuSO(4) and FeCl(2) on phospholipase C (PLC) activity degrading phosphatidylinositol-4,5-bisphosphate (PIP(2)) and phosphatidylinositol (PI) in synaptic plasma membranes (SPM) from the rat brain cortex. We report that 25 microM CuSO(4) and FeCl(2) decreased PIP(2)-PLC activity by 60% and 75%, respectively. However, both compounds had no effect on PI-PLC activity. These data indicated that exclusively PIP(2)-PLC is sensitive to transition metal ions. We suggest that chelators of these metals may protect brain against alteration of phosphoinositide metabolism and might be beneficial in the treatment of neurodegenerative diseases.
Zambrzycka
Agata
A
Department of Cellular Signaling, Medical Research Center, Polish Academy of Sciences, Pawińskiego 5, PL 02-106 Warsaw, Poland. agatazambrzycka@hotmail.com
Cakała
Magdalena
M
Kamińska
Monika
M
D000818:Animals; D001673:Biodegradation, Environmental / Q000187:drug effects*; D002540:Cerebral Cortex / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D019327:Copper Sulfate / Q000494:pharmacology; D005296:Ferrous Compounds / Q000494:pharmacology; D017403:In Situ Hybridization; D007477:Ions; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism*; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D013570:Synaptic Membranes / Q000187:drug effects / Q000378:metabolism; D028561:Transition Elements / Q000009:adverse effects* / Q000737:chemistry; D010738:Type C Phospholipases / Q000187:drug effects / Q000502:physiology*
D005296:Ferrous Compounds; D007477:Ions; D019269:Phosphatidylinositol 4,5-Diphosphate; D018129:Phosphatidylinositol Phosphates; D028561:Transition Elements; D010738:Type C Phospholipases; D019327:Copper Sulfate; C029451:ferrous chloride