Journal article
Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti-renal cancer drug
Journal of molecular recognition, Vol.31(4), p.n/a
04/2018
DOI: 10.1002/jmr.2688
PMID: 29178153
Abstract
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.
Details
- Title: Subtitle
- Global transition of human serum albumin to prefibrillar aggregates induced by temsirolimus: Insight into implications of anti-renal cancer drug
- Creators
- Anas Shamsi - Aligarh Muslim UniversityAzaj Ahmed - Aligarh Muslim UniversityBilqees Bano - Aligarh Muslim University
- Resource Type
- Journal article
- Publication Details
- Journal of molecular recognition, Vol.31(4), p.n/a
- DOI
- 10.1002/jmr.2688
- PMID
- 29178153
- NLM abbreviation
- J Mol Recognit
- ISSN
- 0952-3499
- eISSN
- 1099-1352
- Language
- English
- Date published
- 04/2018
- Academic Unit
- Internal Medicine
- Record Identifier
- 9985178664502771
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