دورية أكاديمية
Urea ameliorates trimethylamine N-oxide-Induced aggregation of intrinsically disordered α-casein protein: the other side of the urea-methylamine counteraction.
| العنوان: | Urea ameliorates trimethylamine N-oxide-Induced aggregation of intrinsically disordered α-casein protein: the other side of the urea-methylamine counteraction. |
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| المؤلفون: | Bhat MY; Department of Clinical Biochemistry, University of Kashmir, Srinagar, India., Mir IA; Department of Biotechnology, University of Kashmir, Srinagar, India., Ul Hussain M; Department of Biotechnology, University of Kashmir, Srinagar, India., Singh LR; Dr. B. R. Ambedkar Center for Biomedical Research, University of Delhi, Delhi, India., Dar TA; Department of Clinical Biochemistry, University of Kashmir, Srinagar, India. |
| المصدر: | Journal of biomolecular structure & dynamics [J Biomol Struct Dyn] 2023 May; Vol. 41 (8), pp. 3659-3666. Date of Electronic Publication: 2022 Mar 22. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Taylor & Francis Country of Publication: England NLM ID: 8404176 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1538-0254 (Electronic) Linking ISSN: 07391102 NLM ISO Abbreviation: J Biomol Struct Dyn Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: June 2012- : Oxon, UK : Taylor & Francis Original Publication: Guilderland, NY : Adenine Press, [c1983- |
| مواضيع طبية MeSH: | Intrinsically Disordered Proteins*, Humans ; Caseins ; Amyloid beta-Peptides ; Urea/pharmacology ; HEK293 Cells ; Methylamines/pharmacology |
| مستخلص: | Trimethylamine N-oxide (TMAO) is generally accumulated by organisms and cells to cope with denaturing effects of urea/hydrodynamic pressure on proteins and can even reverse misfolded or aggregated proteins so as to sustain proteostasis. However, most of the work regarding this urea-TMAO counteraction has been performed on folded proteins. Compelling evidence of aggregation of intrinsically disordered proteins (IDPs) like tau, α-synuclein, amyloid β etc., by TMAO and its potential to impact various protein processes in absence of stressing agents (such as urea) suggests that the contrary feature of interaction profiles of urea and TMAO maximizes their chances of offsetting the perturbing effects of each other. Recently, our lab observed that TMAO induces aggregation of α-casein, a model IDP. In this context, the present study, for the first time, evaluated urea for its potential to counteract the TMAO-induced aggregation of α-casein. It was observed that, at the biologically relevant ratios of 2:1 or 3:1 (urea:TMAO), urea was able to inhibit TMAO-induced aggregation of α-casein. However, urea did not reverse the effects of TMAO on α-casein. In addition to this, α-casein in presence of 1:1 and 2:1 urea:TMAO working ratios show aggregation-induced cytotoxic effect on HEK-293, Neuro2A and HCT-116 cell lines but not in presence of 3:1 working ratio, as there was no aggregation at all. The study infers that the accumulation of TMAO alone in the cells, in absence of stress (such as urea), might result in loss of conformational flexibility and aggregation of IDPs in TMAO accumulating organisms.Communicated by Ramaswamy H. Sarma. |
| فهرسة مساهمة: | Keywords: TMAO; Urea; aggregation; counteraction; intrinsically disordered proteins |
| المشرفين على المادة: | 0 (Intrinsically Disordered Proteins) 0 (Caseins) FLD0K1SJ1A (trimethyloxamine) 0 (Amyloid beta-Peptides) 8W8T17847W (Urea) 0 (Methylamines) |
| تواريخ الأحداث: | Date Created: 20220322 Date Completed: 20230502 Latest Revision: 20230503 |
| رمز التحديث: | 20240628 |
| DOI: | 10.1080/07391102.2022.2053744 |
| PMID: | 35315738 |
| قاعدة البيانات: | MEDLINE |
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Full Text Finder | تدمد: | 1538-0254 |
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| DOI: | 10.1080/07391102.2022.2053744 |