Effect of aluminum chloride, -citrate, and -maltol on the calcium-mediated degradation of neurofilament proteins.
Aluminum (Al) has been observed to cause neurofilament protein accumulation in both experimental animals and cultured cells. Impairment of axonal transport is thought to be a mechanism of toxicity. Inhibition of the degradation of neurofilament proteins, however, resulting in accumulation of these proteins may be an alternative mechanism for Al toxicity. In the present study, the effect of calcium (Ca) on the proteolysis of the neurofilament triplet proteins by calcium-activated neutral proteases (CANP) was studied in the isolated sciatic nerve explants. The extent of the degradation was found to be dependent on the Ca concentration. The effect of Al chloride, -citrate and -maltol on the calcium-induced degradation was studied. No effect of any of the Al compounds was observed, suggesting that the metal may exert its neurotoxic effect via a mechanism other than impairment of neurofilament proteolysis. Maltol itself was found to enhance the effect of Ca on the degradation of neurofilament proteins, probably by facilitating the movement of Ca across the neuronal membrane.
Van Ginkel
M F
MF
Toxicology Laboratory, University Hospital Leiden, The Netherlands.
Heijink
E
E
Dekker
P B
PB
Miralem
T
T
van der Voet
G B
GB
de Wolff
F A
FA
D000535:Aluminum / Q000494:pharmacology*; D000077410:Aluminum Chloride; D017607:Aluminum Compounds; D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D002951:Citrates / Q000494:pharmacology*; D019343:Citric Acid; D005260:Female; D066298:In Vitro Techniques; D008970:Molecular Weight; D016900:Neurofilament Proteins / Q000378:metabolism*; D009942:Organometallic Compounds / Q000494:pharmacology*; D011753:Pyrones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012584:Sciatic Nerve / Q000187:drug effects / Q000378:metabolism
D017607:Aluminum Compounds; D002712:Chlorides; D002951:Citrates; D016900:Neurofilament Proteins; D009942:Organometallic Compounds; D011753:Pyrones; C067527:aluminum maltolate; D019343:Citric Acid; D000077410:Aluminum Chloride; D000535:Aluminum; D002118:Calcium