| Author/Editor | Soomets, Ursel; Mahlapuu, Riina; Tehranian, Roya; Jarvet, J; Karelson, Ello; Zilmer, Mihkel; Iverfeldt, Kerstin; Zorko, Matjaž; Graeslund, Astrid; Langel, Ulo | |
| Title | Regulation of GTPase and adenylate cyclase activity by amyloid beta-peptide and its fragments in rat brain tissue | |
| Type | članek | |
| Source | Brain Res | |
| Vol. and No. | Letnik 850 | |
| Publication year | 1999 | |
| Volume | str. 179-188 | |
| Language | eng | |
| Abstract | Modulation of GTPase and adenylate cyclase (ATP pyrophosphate-lyase, EC 4.6.1.1) activity by Alzheimer;s disease related amyloid hippocampus and frontal cortex. In both tossues, the activity of GTPase and adenylate cyclase was upregulated by A beta(25-35), whereas A beta(12-28) did not have any significant effect on the GTPase activity and only weakly influenced adenylate cyclase. A beta(1-42), similar to A beta(25-35), stimulated the GTPase activity in both tossues and adenylate cyclase activity in ventral hippocampal membranes. Surprisingly, A beta(1-42) did not have a signifivant effects on adenylate cyclase activity in the cortical membranes. At high concentrations of A beta(25-35) and A beta(1-42), decreased or no activation of adenylate cyclase was observed. The activation of GTPase at high concentrations od A beta(25-35) was pertussis toxin sensitive, suggesting that this effects id mediated by G1/G0 proteins. Addition of glutathione and N-acetyl-L-cysteine, two well-known antiooxidants, at 1.5 and 0.5 mM, respectively, decreased A beta(25-35) stimulated adenylate cyclase activity in both tissues. Lys-A beta(16-20), a hexapeptide shown previously to bind to the same sequence in A beta-peptide, and prevent fibril formation, decreased stimulation of adenylate cyclase activity by A beta(25-35), however, NMR diffusion measurements with the two peptides showed that this effect was not due to interactions between the two and that A beta(25-35) was active in a monomeric form. Our data strongly suggest that A beta and its fragments may affect G-protein coupled signal transduction systems, although the mechanism of this interaction is not fully understood. | |
| Descriptors | BRAIN GTP PHOSPHOHYDROLASE ADENYL CYCLASE ALZHEIMER'S DISEASE AMYLOID BETA-PROTEIN RATS PERTUSSIS TOXINS GLUTATHIONE ACETYLCYSTEINE NUCLEAR MAGNETIC RESONANCE |