Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin

Naeem, Aabgeena; Iram, Afshin; Bhat, Sheraz A.

doi:10.1016/j.ijbiomac.2015.05.045

Cited by 28 publications

(16 citation statements)

References 39 publications

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“…Increase in fluorescence intensity is approximately 5 times as compared to native protein. This increased ThT fluorescence can be attributed to the fact that native HSA is transformed into non‐native conformation in the presence of temsirolimus via protein‐protein interactions resulting in formation of prefibrillar aggregates . When molecules of dye get immobilized in the specific binding sites of amyloid structure, an increase in fluorescence intensity was observed.…”

Section: Resultsmentioning

confidence: 99%

“…When HSA is incubated with temsirolimus for 20 days, temsirolimus induces the formation of prefibrillar aggregates of HSA. Many recent studies have reported these prefibrillar aggregates to be cytotoxic in nature . These structures are exciting to study further as these are thought to cause cell death .…”

Section: Resultsmentioning

confidence: 99%

“…Many recent studies have reported these prefibrillar aggregates to be cytotoxic in nature. 17 These structures are exciting to study further as these are thought to cause cell death. 23 The cytotoxicity of prefibrillar aggregates can be attributed to greater accessibility of non-polar side chains and other regions of the polypeptide moiety compared to amyloid aggregates.…”

Section: Discussionmentioning

confidence: 99%

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Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

Shamsi

Ahmed

Bano

2017

J of Molecular Recognition

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In our study, we have characterized the prefibrillar aggregates of human serum albumin (HSA) induced by temsirolimus, anti-renal cancer drug. Molecular docking was retorted to confirm binding of HSA and temsirolimus. Temsirolimus caused the structural transition of native HSA to non-native species after prolonged incubation of 20 days. These non-native species were characterized as prefibrillar aggregates as evident by decreased intrinsic fluorescence and enhanced 8-anilino-1-naphthalene-sulphonic acid (ANS) fluorescence. Further, enhanced thioflavin T fluorescence and shift in congo red (CR) spectra of temsirolimus-incubated HSA as compared to native HSA are suggestive of global transition of HSA in presence of temsirolimus towards prefibrillar aggregates. Circular dichroism spectroscopy revealed α to β transition upon prolonged incubation with temsirolimus suggesting the formation of prefibrillar aggregates as aggregates are known to possess high β content. Scanning electron microscopy confirmed these non-native species to be prefibrillar aggregates evident by observed sheath-like structures. Comet assay was retorted to confirm genotoxic nature of these prefibrillar aggregates; DNA damage was observed for temsirolimus-incubated HSA confirming the genotoxic nature of prefibrillar aggregates. These prefibrillar aggregates are observed at heart of many pathological conditions, thus making our study clinically significant.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

Shamsi

Ahmed

Bano

2017

J of Molecular Recognition

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“…The crystal structures of neither hUb nor E16V mutant are affected by the presence of TFE. [32,33] NMR, CD, and ATR-FTIR characterization of hUb and E16V mutant in the presence of TFE 1 H, 15 NH SQC spectra of hUb and E16V were recorded in 1mm phosphate buffer( pH 7) in the presence of 15 %v /v TFE at 25 8C. Unlike the protein folding, as ignificant effect of TFE was observed on the Zn 2 + binding sites.…”

Section: X-ray Structures Of Hub and E16v Mutant Crystallized In The mentioning

confidence: 99%

Aggregation Pathways of Native‐Like Ubiquitin Promoted by Single‐Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium

Fermani

Calvaresi

Mangini

et al. 2018

Chemistry A European J

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Ubiquitin-positive protein aggregates are biomarkers of neurodegeneration, but the molecular mechanism responsible for their formation and accumulation is still unclear. Possible aggregation pathways of human ubiquitin (hUb) promoted by both intrinsic and extrinsic factors, are here investigated. By a computational analysis, two different hUb dimers are indicated as possible precursors of amyloid-like structures, but their formation is disfavored by an electrostatic repulsion involving Glu16 and other carboxylate residues present at the dimer interface. Experimental data on the E16V mutant of hUb shows that this single-point mutation, although not affecting the overall protein conformation, promotes protein aggregation. It is sufficient to shift the same mutation by only two residues (E18V) to regain the behavior of wild-type hUb. The neutralization of Glu16 negative charge by a metal ion and a decrease of the dielectric constant of the medium by addition of trifluoroethanol (TFE), also promote hUb aggregation. The outcomes of this research have important implications for the prediction of physiological parameters that favor aggregate formation.

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“…At 40% TFE, native Fib depicts 55 times increased ThT fluorescence intensity relative to native (curve 2) indicating the formation of aggregates. ThT is composed of benzothiazole and benzaminic rings freely rotating around a shared C-C bond[22]. Fib at 30, 40 and 50% TFE on incubation with ThT restricts this rotation generating fluorescence at 490 nm(Fig.…”

mentioning

confidence: 99%

Aggregation of intrinsically disordered fibrinogen as the influence of backbone conformation

Naeem

Bhat

Iram

et al. 2016

Archives of Biochemistry and Biophysics

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Anesthetic 2,2,2-trifluoroethanol induces amyloidogenesis and cytotoxicity in human serum albumin

Cited by 28 publications

References 39 publications

Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti‐renal cancer drug

Aggregation Pathways of Native‐Like Ubiquitin Promoted by Single‐Point Mutation, Metal Ion Concentration, and Dielectric Constant of the Medium

Aggregation of intrinsically disordered fibrinogen as the influence of backbone conformation

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