Authors:	Breder-Bonk, Christina Docter, Dominic Barz, Matthias Strieth, Sebastian Knauer, Shirley K. Gül, Désirée Stauber, Roland H.
Title:	The apoptosis inhibitor protein Survivin is a critical cytoprotective resistor against silica-based nanotoxicity
Online publication date:	19-Feb-2024
Year of first publication:	2023
Language:	english
Abstract:	Exposure to nanoparticles is inevitable as they become widely used in industry, cosmetics, and foods. However, knowledge of their (patho)physiological effects on biological entry routes of the human body and their underlying molecular mechanisms is still fragmented. Here, we examined the molecular effects of amorphous silica nanoparticles (aSiNPs) on cell lines mimicking the alveolar-capillary barrier of the lung. After state-of-the-art characterization of the used aSiNPs and the cell model, we performed cell viability-based assays and a protein analysis to determine the aSiNP-induced cell toxicity and underlying signaling mechanisms. We revealed that aSiNPs induce apoptosis in a dose-, time-, and size-dependent manner. aSiNP-induced toxicity involves the inhibition of pro-survival pathways, such as PI3K/AKT and ERK signaling, correlating with reduced expression of the anti-apoptotic protein Survivin on the protein and transcriptional levels. Furthermore, induced Survivin overexpression mediated resistance against aSiNP-toxicity. Thus, we present the first experimental evidence suggesting Survivin as a critical cytoprotective resistor against silica-based nanotoxicity, which may also play a role in responses to other NPs. Although Survivin’s relevance as a biomarker for nanotoxicity needs to be demonstrated in vivo, our data give general impetus to investigate the pharmacological modulation of Survivin`s functions to attenuate the harmful effects of acute or chronic inhalative NP exposure.
DDC:	610 Medizin 610 Medical sciences
Institution:	Johannes Gutenberg-Universität Mainz
Department:	FB 04 Medizin
Place:	Mainz
ROR:	https://ror.org/023b0x485
DOI:	http://doi.org/10.25358/openscience-10041
Version:	Published version
Publication type:	Zeitschriftenaufsatz
Document type specification:	Scientific article
License:	CC BY
Information on rights of use:	https://creativecommons.org/licenses/by/4.0/
Journal:	Nanomaterials 13 18
Pages or article number:	2546
Publisher:	MDPI
Publisher place:	Basel
Issue date:	2023
ISSN:	2079-4991
Publisher URL:	https://doi.org/10.3390/nano13182546
Publisher DOI:	10.3390/nano13182546
Appears in collections:	DFG-491381577-G