SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction
Superoxide dismutase (SOD) family isoenzymes, SOD1, SOD2, and SOD3, synthesize hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which regulates the signal transduction. H<sub>2</sub>O<sub>2</sub> is a second messenger able to enter into the cells throug...
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-04-01
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| Series: | Antioxidants |
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| Online Access: | https://www.mdpi.com/2076-3921/10/5/635 |
| _version_ | 1797536844451151872 |
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| author | Alessia Parascandolo Mikko O. Laukkanen |
| author_facet | Alessia Parascandolo Mikko O. Laukkanen |
| author_sort | Alessia Parascandolo |
| collection | DOAJ |
| description | Superoxide dismutase (SOD) family isoenzymes, SOD1, SOD2, and SOD3, synthesize hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which regulates the signal transduction. H<sub>2</sub>O<sub>2</sub> is a second messenger able to enter into the cells through aquaporin 3 cell membrane channels and to modify protein tyrosine phosphatase activity. SOD3 has been shown to activate signaling pathways in tissue injuries, inflammation, and cancer models. Similar to the H<sub>2</sub>O<sub>2</sub> response in the cells, the cellular response of SOD3 is dose-dependent; even a short supraphysiological concentration reduces the cell survival and activates the growth arrest and apoptotic signaling, whereas the physiological SOD3 levels support its growth and survival. In the current work, we studied the signaling networks stimulated by SOD3 overexpression demonstrating a high diversity in the activation of signaling cascades. The results obtained suggest that SOD3, although inducing cell growth and affecting various biological processes, does not cause detectable long-term DNA aberrations. Therefore, according to the present data, SOD3 is not a mutagen. Additionally, we compared SOD3-driven immortalized mouse embryonic fibroblasts to SV40 immortalized NIH3T3 cells, demonstrating a marked difference in the activation of cellular kinases. The data presented may contain important druggable targets to abrogate unwanted cell growth. |
| first_indexed | 2024-03-10T12:06:35Z |
| format | Article |
| id | doaj.art-47a8196f165949868a48678647780342 |
| institution | Directory Open Access Journal |
| issn | 2076-3921 |
| language | English |
| last_indexed | 2024-03-10T12:06:35Z |
| publishDate | 2021-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Antioxidants |
| spelling | doaj.art-47a8196f165949868a486786477803422023-11-21T16:30:32ZengMDPI AGAntioxidants2076-39212021-04-0110563510.3390/antiox10050635SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal TransductionAlessia Parascandolo0Mikko O. Laukkanen1Center for Experimental Endocrinology and Oncology (IEOS), CNR, Via Pansini 5, 80131 Naples, ItalyCenter for Experimental Endocrinology and Oncology (IEOS), CNR, Via Pansini 5, 80131 Naples, ItalySuperoxide dismutase (SOD) family isoenzymes, SOD1, SOD2, and SOD3, synthesize hydrogen peroxide (H<sub>2</sub>O<sub>2</sub>), which regulates the signal transduction. H<sub>2</sub>O<sub>2</sub> is a second messenger able to enter into the cells through aquaporin 3 cell membrane channels and to modify protein tyrosine phosphatase activity. SOD3 has been shown to activate signaling pathways in tissue injuries, inflammation, and cancer models. Similar to the H<sub>2</sub>O<sub>2</sub> response in the cells, the cellular response of SOD3 is dose-dependent; even a short supraphysiological concentration reduces the cell survival and activates the growth arrest and apoptotic signaling, whereas the physiological SOD3 levels support its growth and survival. In the current work, we studied the signaling networks stimulated by SOD3 overexpression demonstrating a high diversity in the activation of signaling cascades. The results obtained suggest that SOD3, although inducing cell growth and affecting various biological processes, does not cause detectable long-term DNA aberrations. Therefore, according to the present data, SOD3 is not a mutagen. Additionally, we compared SOD3-driven immortalized mouse embryonic fibroblasts to SV40 immortalized NIH3T3 cells, demonstrating a marked difference in the activation of cellular kinases. The data presented may contain important druggable targets to abrogate unwanted cell growth.https://www.mdpi.com/2076-3921/10/5/635extracellular superoxide dismutasesod3signal transductioncancerproliferationmigration |
| spellingShingle | Alessia Parascandolo Mikko O. Laukkanen SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction Antioxidants extracellular superoxide dismutase sod3 signal transduction cancer proliferation migration |
| title | SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction |
| title_full | SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction |
| title_fullStr | SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction |
| title_full_unstemmed | SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction |
| title_short | SOD3 Is a Non-Mutagenic Growth Regulator Affecting Cell Migration and Proliferation Signal Transduction |
| title_sort | sod3 is a non mutagenic growth regulator affecting cell migration and proliferation signal transduction |
| topic | extracellular superoxide dismutase sod3 signal transduction cancer proliferation migration |
| url | https://www.mdpi.com/2076-3921/10/5/635 |
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