Aluminum interaction with plasma membrane lipids and enzyme metal binding sites and its potential role in Al cytotoxicity.
The trivalent cation aluminum can cause chronic cytotoxicity in plants, animals and microorganisms. It has been suggested that Al interaction with cell membranes and enzyme metal binding sites may be involved in Al cytotoxicity. In this study, the binding of Al to microsomes and liposomes was found to be lipid dependent with the signal transduction element phosphatidylinositol-4,5-bisphosphate having the highest affinity for Al with an Al:lipid stoichiometry of 1:1. Al binding was only reduced in the presence of high concentrations of Ca2+ (> 1 mM). Both citrate and, to a lesser extent, malate were capable of preventing Al lipid binding, which is consistent with the involvement of these organic acids in a recently described Al detoxification mechanism in plants. The effects of AICl3, Al-citrate and ZnSO4 on metal-dependent enzyme activities (enolase, pyruvate kinase, H+-ATPase, myosin, Calpain, proteinase K, phospholipase A2 and arginase) was assayed in vitro. While Zn2+ was capable of inhibiting all the enzymes except the H+-ATPase, AlCl3 and Al-citrate had minimal effects except for with phospholipase A2 where an interaction with AlCl3 occurred. However, this could be negated by the addition of citrate. The results indicate that, contrary to current hypotheses, the toxic mode of Al is not through an interaction with enzymatic catalytic metal binding sites but may be through the interaction with specific membrane lipids.
Jones
D L
DL
School of Agricultural and Forest Sciences, University of Wales, Bangor, Gwynedd, UK. d.jones@bangor.ac.uk
Kochian
L V
LV
D000535:Aluminum / Q000378:metabolism* / Q000633:toxicity; D000077410:Aluminum Chloride; D017607:Aluminum Compounds / Q000378:metabolism; D000818:Animals; D002118:Calcium / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism; D002154:Calpain / Q000378:metabolism; D002712:Chlorides / Q000378:metabolism; D002951:Citrates / Q000378:metabolism; D008081:Liposomes / Q000378:metabolism; D008274:Magnesium / Q000378:metabolism; D008345:Manganese / Q000378:metabolism; D008563:Membrane Lipids / Q000097:blood*; D008670:Metals / Q000378:metabolism*; D008861:Microsomes / Q000378:metabolism; D010741:Phospholipases A / Q000378:metabolism; D054467:Phospholipases A2; D010751:Phosphopyruvate Hydratase / Q000378:metabolism; D006180:Proton-Translocating ATPases / Q000378:metabolism; D011770:Pyruvate Kinase / Q000378:metabolism; D014908:Triticum
D017607:Aluminum Compounds; D002712:Chlorides; D002951:Citrates; D008081:Liposomes; D008563:Membrane Lipids; D008670:Metals; D000077410:Aluminum Chloride; D008345:Manganese; D000535:Aluminum; D011770:Pyruvate Kinase; D010741:Phospholipases A; D054467:Phospholipases A2; D002154:Calpain; D006180:Proton-Translocating ATPases; D010751:Phosphopyruvate Hydratase; D000252:Calcium-Transporting ATPases; D008274:Magnesium; D002118:Calcium