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beta-Amyloid(25-35) inhibits the activity of inositol(1,4,5)-trisphosphate-5-phosphatase
1Department of Pharmacology and Clinical Neuroscience, Umeå University, Sweden.
Abstract:
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.
Insights
Beta-amyloid (A beta) peptides impact cell calcium. This study found that A beta(25-35) inhibits Ins(1,4,5)P3-5-phosphatase, affecting inositol trisphosphate metabolism but not significantly impacting calcium homeostasis.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Beta-amyloid (A beta) peptides are implicated in cellular calcium disruption.
- Inositol 1,4,5-trisphosphate 5-phosphatase (Ins(1,4,5)P3-5-phosphatase) plays a role in calcium signaling pathways.
Purpose of the Study:
- To investigate the effects of A beta(25-35) on the activity of soluble Ins(1,4,5)P3-5-phosphatase.
- To determine if A beta peptides influence the metabolism of inositol trisphosphate.
Main Methods:
- Assay of soluble rat cerebellar Ins(1,4,5)P3-5-phosphatase activity.
- Treatment with A beta(25-35) peptide and dithiothreitol (DTT).
- Assessment of enzyme sensitivity to glucose-6-phosphate and phytic acid.
Main Results:
- A beta(25-35) significantly inhibited soluble Ins(1,4,5)P3-5-phosphatase activity.
- Dithiothreitol (DTT) increased the enzyme's activity.
- A beta(35-25) also inhibited the enzyme, but with lower potency than A beta(25-35).
- The enzyme's sensitivity to glucose-6-phosphate and phytic acid was not significantly altered.
Conclusions:
- A beta(25-35) affects Ins(1,4,5)P3 metabolism by inhibiting Ins(1,4,5)P3-5-phosphatase.
- The observed inhibition potency is unlikely to be a major contributor to the broader effects of A beta peptides on calcium homeostasis.