title: Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin.
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.
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India. Electronic address: aabgeenanaim@gmail.com.
authors.forename: Aabgeena
authors.initials: A
authors.lastname: Naeem
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Afshin
authors.initials: A
authors.lastname: Iram
authors.affiliation: Department of Biochemistry, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India.
authors.forename: Sheraz Ahmed
authors.initials: SA
authors.lastname: Bhat
mesh_terms: D000777:Anesthetics / Q000737:chemistry* / Q000494:pharmacology; D052160:Benzothiazoles; D020552:Comet Assay; D003224:Congo Red; D005456:Fluorescent Dyes; D006801:Humans; D006860:Hydrogen Bonding; D057927:Hydrophobic and Hydrophilic Interactions; D008214:Lymphocytes / Q000737:chemistry / Q000166:cytology / Q000187:drug effects; D009691:Nucleic Acid Denaturation / Q000187:drug effects; D061251:Primary Cell Culture; D066329:Protein Aggregates; D011485:Protein Binding; D017510:Protein Folding; D017433:Protein Structure, Secondary; D012709:Serum Albumin / Q000737:chemistry*; D012996:Solutions; D013844:Thiazoles; D014270:Trifluoroethanol / Q000737:chemistry* / Q000494:pharmacology
chemical_list: D000777:Anesthetics; D052160:Benzothiazoles; D005456:Fluorescent Dyes; D066329:Protein Aggregates; D012709:Serum Albumin; D012996:Solutions; D013844:Thiazoles; C009462:thioflavin T; D003224:Congo Red; D014270:Trifluoroethanol
keywords: Aggregates; Cytotoxic nature; TEM