Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach
The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells...
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MDPI AG
2025-05-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/14/5/571 |
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| author | Alessandra Cimbalo Massimo Frangiamone Lara Manyes |
| author_facet | Alessandra Cimbalo Massimo Frangiamone Lara Manyes |
| author_sort | Alessandra Cimbalo |
| collection | DOAJ |
| description | The aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells were exposed to (A) mycotoxins, (B) the digesta of mycotoxin-contaminated bread formulated with P, or (C) bread enriched with FW + P. A proteomic approach using HPLC-MS/MS-QTOF was then employed to characterize the metabolic pathways affected by the presence of these components, as well as their ability to modulate the toxic effects exacerbated by mycotoxins. Gene ontology functional analysis revealed proteins primarily associated with nucleosome structure, such as the H3-H4 tetramer, H2A-H2B dimer, and HIRA, which were overexpressed in the presence of mycotoxins and, interestingly, downregulated with the addition of the functional ingredients. Additionally, important metabolic pathways associated with the RHO GTPase family, estrogen-dependent gene expression, and androgen receptor transcription stimulated by PKN1 activation were discovered. Network interaction analysis highlighted the modulation of cytoskeletal dynamics, cell migration, and stress responses. These findings provide novel insights into the neuroprotective potential of functional food components, supporting their use in mitigating mycotoxin-induced neuronal damage and opening new avenues for dietary-based neuroprotection strategies. |
| format | Article |
| id | doaj-art-bcded204b1b74fb48a5e2febc44c6902 |
| institution | DOAJ |
| issn | 2076-3921 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj-art-bcded204b1b74fb48a5e2febc44c69022025-08-20T03:14:39ZengMDPI AGAntioxidants2076-39212025-05-0114557110.3390/antiox14050571Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic ApproachAlessandra Cimbalo0Massimo Frangiamone1Lara Manyes2Biotech Agrifood, Faculty of Pharmacy and Food Sciences, Universitat de València, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainBiotech Agrifood, Faculty of Pharmacy and Food Sciences, Universitat de València, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainBiotech Agrifood, Faculty of Pharmacy and Food Sciences, Universitat de València, Avda. Vicent Andrés Estellés s/n, 46100 Burjassot, SpainThe aim of this work is to highlight the beneficial effects of bioactive peptides present in fermented whey (FW) and carotenoids from pumpkin (P) against the pro-oxidant effects of aflatoxin B1 and ochratoxin A at the neuronal level. For this purpose, SH-SY5Y human neuroblastoma differentiated cells were exposed to (A) mycotoxins, (B) the digesta of mycotoxin-contaminated bread formulated with P, or (C) bread enriched with FW + P. A proteomic approach using HPLC-MS/MS-QTOF was then employed to characterize the metabolic pathways affected by the presence of these components, as well as their ability to modulate the toxic effects exacerbated by mycotoxins. Gene ontology functional analysis revealed proteins primarily associated with nucleosome structure, such as the H3-H4 tetramer, H2A-H2B dimer, and HIRA, which were overexpressed in the presence of mycotoxins and, interestingly, downregulated with the addition of the functional ingredients. Additionally, important metabolic pathways associated with the RHO GTPase family, estrogen-dependent gene expression, and androgen receptor transcription stimulated by PKN1 activation were discovered. Network interaction analysis highlighted the modulation of cytoskeletal dynamics, cell migration, and stress responses. These findings provide novel insights into the neuroprotective potential of functional food components, supporting their use in mitigating mycotoxin-induced neuronal damage and opening new avenues for dietary-based neuroprotection strategies.https://www.mdpi.com/2076-3921/14/5/571bioactive peptidescarotenoidsproteomicsSH-SY5YHPLC-MS/MS-QTOF |
| spellingShingle | Alessandra Cimbalo Massimo Frangiamone Lara Manyes Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach Antioxidants bioactive peptides carotenoids proteomics SH-SY5Y HPLC-MS/MS-QTOF |
| title | Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach |
| title_full | Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach |
| title_fullStr | Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach |
| title_full_unstemmed | Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach |
| title_short | Deepening the Modulatory Activity of Bioactive Compounds Against AFB1- and OTA-Induced Neuronal Toxicity Through a Proteomic Approach |
| title_sort | deepening the modulatory activity of bioactive compounds against afb1 and ota induced neuronal toxicity through a proteomic approach |
| topic | bioactive peptides carotenoids proteomics SH-SY5Y HPLC-MS/MS-QTOF |
| url | https://www.mdpi.com/2076-3921/14/5/571 |
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