Molecular understanding of Abeta peptide interaction with isoflurane, propofol, and thiopental: NMR spectroscopic study.
Abeta peptide is the major component of senile plaques (SP), which accumulate in the brain of a patient with Alzheimer's disease (AD). A recent report indicated that isoflurane enhanced Abeta oligomerization (micro-aggregation) and subsequent cytotoxicity of the Abeta peptide. A separate study showed that a clinically relevant concentration of isoflurane induces apoptosis and increases Abeta production in a human neuroglioma cell line. In vitro studies have indicated that halothane interacts specifically with Abeta peptide to induce oligomerization and that Abeta42 oligomerizes faster than Abeta40. The specific interactions of isoflurane, propofol, and thiopental with uniformly 15N labeled Abeta40 and Abeta42 peptide were investigated using multidimensional nuclear magnetic resonance (NMR) experiments. We found that isoflurane and propofol (at higher concentration) interact with Abeta40 peptides and induce Abeta oligomerization. Thiopental does not interact with specific residues (G29, A30, and I31) of Abeta40; hence, the peptide remains in the monomeric form. On the basis of our NMR study, thiopental does not oligomerize Abeta40 even at higher concentrations.
Mandal
Pravat K
PK
Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, Pennsylvania 15213, USA. mandalp@upmc.edu
Williams
John P
JP
Mandal
Ratna
R
D016229:Amyloid beta-Peptides / Q000737:chemistry*; D000777:Anesthetics / Q000737:chemistry*; D007530:Isoflurane / Q000737:chemistry*; D008823:Micelles; D019906:Nuclear Magnetic Resonance, Biomolecular; D010446:Peptide Fragments / Q000737:chemistry*; D015742:Propofol / Q000737:chemistry*; D020836:Protein Structure, Quaternary; D012967:Sodium Dodecyl Sulfate; D013874:Thiopental / Q000737:chemistry*
D016229:Amyloid beta-Peptides; D000777:Anesthetics; D008823:Micelles; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D012967:Sodium Dodecyl Sulfate; D007530:Isoflurane; D013874:Thiopental; D015742:Propofol