A Conserved Mechanism for Hormesis in Molecular Systems.

Autor: Greenwood SN; Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA., Belz RG; University of Hohenheim, Hans-Ruthenberg Institute, Stuttgart, Germany., Weiser BP; Department of Molecular Biology, Rowan University School of Osteopathic Medicine, Stratford, NJ, USA.
Jazyk: angličtina
Zdroj: Dose-response : a publication of International Hormesis Society [Dose Response] 2022 Aug 02; Vol. 20 (3), pp. 15593258221109335. Date of Electronic Publication: 2022 Aug 02 (Print Publication: 2022).
DOI: 10.1177/15593258221109335
Abstrakt: Hormesis refers to dose-response phenomena where low dose treatments elicit a response that is opposite the response observed at higher doses. Hormetic dose-response relationships have been observed throughout all of biology, but the underlying determinants of many reported hormetic dose-responses have not been identified. In this report, we describe a conserved mechanism for hormesis on the molecular level where low dose treatments enhance a response that becomes reduced at higher doses. The hormetic mechanism relies on the ability of protein homo-multimers to simultaneously interact with a substrate and a competitor on different subunits at low doses of competitor. In this case, hormesis can be observed if simultaneous binding of substrate and competitor enhances a response of the homo-multimer. We characterized this mechanism of hormesis in binding experiments that analyzed the interaction of homotrimeric proliferating cell nuclear antigen (PCNA) with uracil DNA glycosylase (UNG2) and a fluorescein-labeled peptide. Additionally, the basic features of this molecular mechanism appear to be conserved with at least two enzymes that are stimulated by low doses of inhibitor: dimeric BRAF and octameric glutamine synthetase 2 (GS2). Identifying such molecular mechanisms of hormesis may help explain specific hormetic responses of cells and organisms treated with exogenous compounds.
Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
(© The Author(s) 2022.)
Databáze: MEDLINE
Externí odkaz:
Nepřihlášeným uživatelům se plný text nezobrazuje