beta-Amyloid(25-35) inhibits the activity of inositol(1,4,5)-trisphosphate-5-phosphatase.
beta-amyloid (A beta) peptides are known to disrupt calcium homeostasis in cells. In the present study, the effects of A beta(25-35) upon the activity of soluble Ins(1,4,5)P3-5-phosphatase have been investigated. A beta(25-35) inhibited, and dithiothreitol (DTT) increased the activity of soluble rat cerebellar Ins(1,4,5)P3-5-phosphatase. The change in activity was not accompanied by an obvious change in the sensitivity of the Ins(1,4,5)P3-5-phosphatase to inhibition by glucose-6-phosphate or phytic acid. A beta(35-25) also inhibited soluble Ins(1,4,5)P3-5-phosphatase activity, but at a lower potency than A beta(25-35). It is concluded that A beta(25-35) affects the metabolism of Ins(1,4,5)P3 although the potency is not sufficiently high to contribute to any significant extent to the effects of this peptide upon calcium homeostasis.
Rönnbäck
A
A
Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.
Fowler
C J
CJ
D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004789:Enzyme Activation; D000072181:Inositol Polyphosphate 5-Phosphatases; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D010744:Phosphoric Monoester Hydrolases; D000072181:Inositol Polyphosphate 5-Phosphatases; D002118:Calcium