Abeta peptide interactions with isoflurane, propofol, thiopental and combined thiopental with halothane: a NMR study.
Abeta peptide is the major component of senile plaques (SP) which accumulates in AD (Alzheimer's disease) brain. Reports from different laboratories indicate that anesthetics interact with Abeta peptide and induce Abeta oligomerization. The molecular mechanism of Abeta peptide interactions with these anesthetics was not determined. We report molecular details for the interactions of uniformly (15)N labeled Abeta40 with different anesthetics using 2D nuclear magnetic resonance (NMR) experiments. At high concentrations both isoflurane and propofol perturb critical amino acid residues (G29, A30 and I31) of Abeta peptide located in the hinge region leading to Abeta oligomerization. In contrast, these three specific residues do not interact with thiopental and subsequently no Abeta oligomerization was observed. However, studies with combined anesthetics (thiopental and halothane), showed perturbation of these residues (G29, A30 and I31) and subsequently Abeta oligomerization was found. Perturbation of these specific Abeta residues (G29, A30 and I31) by different anesthetics could play an important role to induce Abeta oligomerization.
Mandal
Pravat K
PK
Western Psychiatric Institute and Clinic, Department of Psychiatry, University of Pittsburgh Medical School, Pittsburgh, PA 15213, USA. Pravat.mandal@gmail.com
Pettegrew
Jay W
JW
D000596:Amino Acids / Q000378:metabolism; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism*; D000777:Anesthetics / Q000737:chemistry / Q000378:metabolism*; D004357:Drug Synergism; D006221:Halothane / Q000737:chemistry / Q000378:metabolism*; D007530:Isoflurane / Q000737:chemistry / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry / Q000378:metabolism; D015742:Propofol / Q000737:chemistry / Q000378:metabolism*; D055503:Protein Multimerization; D013874:Thiopental / Q000737:chemistry / Q000378:metabolism*
D000596:Amino Acids; D016229:Amyloid beta-Peptides; D000777:Anesthetics; D010455:Peptides; D007530:Isoflurane; D013874:Thiopental; D006221:Halothane; D015742:Propofol