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Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin.
- Source :
-
International journal of biological macromolecules [Int J Biol Macromol] 2015 Aug; Vol. 79, pp. 726-35. Date of Electronic Publication: 2015 May 30. - Publication Year :
- 2015
-
Abstract
- Trifluoroethanol (TFE) mimics the membrane environments as it simulates the hydrophobic environment and better stabilizes the secondary structures in peptides owing to its hydrophobicity and hydrogen bond-forming properties. Its dielectric constant approximates that of the interior of proteins and is one-third of that of water. Human serum albumin (HSA) is a biological transporter. The effect of TFE on HSA gives the clue about the conformational changes taking place in HSA on transport of ligands across the biological membranes. At 25% (v/v) and 60% (v/v) TFE, HSA exhibits non-native β-sheet, altered tryptophan fluorescence, exposed hydrophobic clusters, increased thioflavin T fluorescence and prominent red shifted Congo red absorbance, and large hydrodynamic radii suggesting the aggregate formation. Isothermal titration calorimetric results indicate weak binding of TFE and HSA. This suggests that solvent-mediated effects dominate the interaction of TFE and HSA. TEM confirmed prefibrillar at 25% (v/v) and fibrillar aggregates at 60% (v/v) TFE. Comet assay of prefibrillar aggregates showed DNA damage causing cell necrosis hence confirming cytotoxic nature. On increasing concentration of TFE to 80% (v/v), HSA showed retention of native-like secondary structure, increased Trp and ANS fluorescence, a transition from β-sheet to α-helix. Thus, TFE at high concentration possess anti- aggregating potency.<br /> (Copyright © 2015 Elsevier B.V. All rights reserved.)
- Subjects :
- Anesthetics pharmacology
Benzothiazoles
Comet Assay
Congo Red
Fluorescent Dyes
Humans
Hydrogen Bonding
Hydrophobic and Hydrophilic Interactions
Lymphocytes chemistry
Lymphocytes cytology
Lymphocytes drug effects
Nucleic Acid Denaturation drug effects
Primary Cell Culture
Protein Binding
Protein Folding
Protein Structure, Secondary
Solutions
Thiazoles
Trifluoroethanol pharmacology
Anesthetics chemistry
Protein Aggregates
Serum Albumin chemistry
Trifluoroethanol chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1879-0003
- Volume :
- 79
- Database :
- MEDLINE
- Journal :
- International journal of biological macromolecules
- Publication Type :
- Academic Journal
- Accession number :
- 26038104
- Full Text :
- https://doi.org/10.1016/j.ijbiomac.2015.05.045