Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin.
Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin.
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麻醉剂 2,2,2-三氟乙醇可诱导人血清白蛋白淀粉样蛋白生成和细胞毒性。
DOI：
10.1016/j.ijbiomac.2015.05.045
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发表时间：
2015
影响因子：
8.2
通讯作者：
S. A. Bhat
中科院分区：
文献类型：
--
作者：
A. Naeem;Afshin Iram;S. A. Bhat
三氟乙醇（TFE）模拟膜环境，因为它模拟疏水环境，并且由于其疏水性和氢键形成特性而更好地稳定肽中的二级结构。它的介电常数近似于蛋白质内部的介电常数，是水的三分之一。人血清白蛋白（HSA）是一种生物转运蛋白。TFE对HSA的影响提供了关于HSA中发生的配体跨生物膜转运的构象变化的线索。在25%（v/v）和60%（v/v）TFE下，HSA表现出非天然β-折叠、改变的色氨酸荧光、暴露的疏水簇、增加的硫磺素T荧光和显著的红移的刚果红吸光度，以及大的流体动力学半径，表明聚集体形成。等温滴定量热结果表明TFE和HSA的弱结合。这表明，溶剂介导的影响占主导地位的TFE和HSA的相互作用。TEM证实在25%（v/v）时为预纤维状，在60%（v/v）TFE时为纤维状聚集体。前原纤维聚集体的彗星试验显示DNA损伤导致细胞坏死，因此证实了细胞毒性性质。当TFE浓度增加到80%（v/v）时，HSA显示出天然样二级结构的保留，Trp和ANS荧光增加，β-折叠转变为α-螺旋。因此，高浓度的TFE具有一定的抗聚集作用.
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.
DOI：
10.1016/j.bbapap.2010.04.001
发表时间：
2010-07
期刊：
Biochimica et biophysica acta
影响因子：
--
作者：
Biancalana M;Koide S
通讯作者：
Koide S
影响因子：
3
作者：
Khurana, R;Coleman, C;Singh, S
通讯作者：
Singh, S
肾病综合征中白蛋白和免疫球蛋白的代谢。
影响因子：
4.2
作者：
Kaysen,GA;alBander,H
通讯作者：
alBander,H