The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity
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 e...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Nanomaterials |
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| Online Access: | https://www.mdpi.com/2079-4991/13/18/2546 |
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| author | Christina Breder-Bonk Dominic Docter Matthias Barz Sebastian Strieth Shirley K. Knauer Désirée Gül Roland H. Stauber |
| author_facet | Christina Breder-Bonk Dominic Docter Matthias Barz Sebastian Strieth Shirley K. Knauer Désirée Gül Roland H. Stauber |
| author_sort | Christina Breder-Bonk |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T22:22:23Z |
| format | Article |
| id | doaj.art-959508a8fd9145a1864da699a77efff9 |
| institution | Directory Open Access Journal |
| issn | 2079-4991 |
| language | English |
| last_indexed | 2024-03-10T22:22:23Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nanomaterials |
| spelling | doaj.art-959508a8fd9145a1864da699a77efff92023-11-19T12:14:30ZengMDPI AGNanomaterials2079-49912023-09-011318254610.3390/nano13182546The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based NanotoxicityChristina Breder-Bonk0Dominic Docter1Matthias Barz2Sebastian Strieth3Shirley K. Knauer4Désirée Gül5Roland H. Stauber6Molecular and Cellular Oncology, University Medical Center Mainz, Langenbeckstrasse 1, 55101 Mainz, GermanyMolecular and Cellular Oncology, University Medical Center Mainz, Langenbeckstrasse 1, 55101 Mainz, GermanyLeiden Academic Center for Drug Research (LACDR), Leiden University, Einsteinweg 55, 2333 CC Leiden, The NetherlandsDepartment of Otorhinolaryngology, University Medical Center Bonn, Venusberg-Campus 1, 53127 Bonn, GermanyCenter for Medical Biotechnology (ZMB), Department of Molecular Biology II, University of Duisburg-Essen, Universitätsstrasse 5, 45141 Essen, GermanyMolecular and Cellular Oncology, University Medical Center Mainz, Langenbeckstrasse 1, 55101 Mainz, GermanyMolecular and Cellular Oncology, University Medical Center Mainz, Langenbeckstrasse 1, 55101 Mainz, GermanyExposure 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.https://www.mdpi.com/2079-4991/13/18/2546alveolar-capillary barrierlung modelnanotoxicityamorphous silica nanoparticlesinflammationcytotoxic response |
| spellingShingle | Christina Breder-Bonk Dominic Docter Matthias Barz Sebastian Strieth Shirley K. Knauer Désirée Gül Roland H. Stauber The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity Nanomaterials alveolar-capillary barrier lung model nanotoxicity amorphous silica nanoparticles inflammation cytotoxic response |
| title | The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity |
| title_full | The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity |
| title_fullStr | The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity |
| title_full_unstemmed | The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity |
| title_short | The Apoptosis Inhibitor Protein Survivin Is a Critical Cytoprotective Resistor against Silica-Based Nanotoxicity |
| title_sort | apoptosis inhibitor protein survivin is a critical cytoprotective resistor against silica based nanotoxicity |
| topic | alveolar-capillary barrier lung model nanotoxicity amorphous silica nanoparticles inflammation cytotoxic response |
| url | https://www.mdpi.com/2079-4991/13/18/2546 |
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