Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells
Aldehyde dehydrogenase 3A1 (ALDH3A1) oxidizes medium-chain aldehydes to their corresponding carboxylic acids. It is expressed at high rates in the human cornea, where it has been characterized as a multi-functional protein displaying various cytoprotective modes of action. Previous studies identifie...
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MDPI AG
2023-03-01
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| Series: | International Journal of Molecular Sciences |
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| author | Georgia-Persephoni Voulgaridou Vasileios Theologidis Maria Venetikidou Ilias Tsochantaridis Avgi Tsolou Maria Koffa Mihalis I. Panayiotidis Aglaia Pappa |
| author_facet | Georgia-Persephoni Voulgaridou Vasileios Theologidis Maria Venetikidou Ilias Tsochantaridis Avgi Tsolou Maria Koffa Mihalis I. Panayiotidis Aglaia Pappa |
| author_sort | Georgia-Persephoni Voulgaridou |
| collection | DOAJ |
| description | Aldehyde dehydrogenase 3A1 (ALDH3A1) oxidizes medium-chain aldehydes to their corresponding carboxylic acids. It is expressed at high rates in the human cornea, where it has been characterized as a multi-functional protein displaying various cytoprotective modes of action. Previous studies identified its association with the DNA damage response (DDR) pathway. Here, we utilized a stable transfected HCE-2 (human corneal epithelium) cell line expressing ALDH3A1, to investigate the molecular mechanisms underlying the cytoprotective role(s) of ALDH3A1. Our data revealed morphological differences among the ALDH3A1-expressing and the mock-transfected HCE-2 cells accompanied by differential expression of <i>E-cadherin</i>. Similarly, the ALDH3A1/HCE-2 cells demonstrated higher mobility, reduced proliferation, upregulation of <i>ZEB1,</i> and downregulation of <i>CDK3,</i> and <i>p57</i>. The expression of ALDH3A1 also affected cell cycle progression by inducing the sequestration of HCE-2 cells at the G2/M phase. Following 16 h cell treatments with either H<sub>2</sub>O<sub>2</sub> or etoposide, a significantly lower percentage of ALDH3A1/HCE-2 cells were apoptotic compared to the respective treated mock/HCE-2 cells. Interestingly, the protective effect of ALDH3A1 expression under these oxidative and genotoxic conditions was accompanied by a reduced formation of γ-H2AX foci and higher levels of total and phospho (Ser15) p53. Finally, ALDH3A1 was found to be localized both in the cytoplasm and the nucleus of transfected HCE-2 cells. Its cellular compartmentalization was not affected by oxidant treatment, while the mechanism by which ALDH3A1 translocates to the nucleus remains unknown. In conclusion, ALDH3A1 protects cells from both apoptosis and DNA damage by interacting with key homeostatic mechanisms associated with cellular morphology, cell cycle, and DDR. |
| first_indexed | 2024-03-11T06:25:13Z |
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| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T06:25:13Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-9cb5a1eaf63c4469b7ffd411adcf5c6c2023-11-17T11:39:51ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-03-01246584510.3390/ijms24065845Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial CellsGeorgia-Persephoni Voulgaridou0Vasileios Theologidis1Maria Venetikidou2Ilias Tsochantaridis3Avgi Tsolou4Maria Koffa5Mihalis I. Panayiotidis6Aglaia Pappa7Department of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceDepartment of Cancer Genetics, Therapeutics & Ultrastructural Pathology, The Cyprus Institute of Neurology & Genetics, Ayios Dometios, Nicosia 2371, CyprusDepartment of Molecular Biology and Genetics, School of Health Sciences, Democritus University of Thrace, 68100 Alexandroupolis, GreeceAldehyde dehydrogenase 3A1 (ALDH3A1) oxidizes medium-chain aldehydes to their corresponding carboxylic acids. It is expressed at high rates in the human cornea, where it has been characterized as a multi-functional protein displaying various cytoprotective modes of action. Previous studies identified its association with the DNA damage response (DDR) pathway. Here, we utilized a stable transfected HCE-2 (human corneal epithelium) cell line expressing ALDH3A1, to investigate the molecular mechanisms underlying the cytoprotective role(s) of ALDH3A1. Our data revealed morphological differences among the ALDH3A1-expressing and the mock-transfected HCE-2 cells accompanied by differential expression of <i>E-cadherin</i>. Similarly, the ALDH3A1/HCE-2 cells demonstrated higher mobility, reduced proliferation, upregulation of <i>ZEB1,</i> and downregulation of <i>CDK3,</i> and <i>p57</i>. The expression of ALDH3A1 also affected cell cycle progression by inducing the sequestration of HCE-2 cells at the G2/M phase. Following 16 h cell treatments with either H<sub>2</sub>O<sub>2</sub> or etoposide, a significantly lower percentage of ALDH3A1/HCE-2 cells were apoptotic compared to the respective treated mock/HCE-2 cells. Interestingly, the protective effect of ALDH3A1 expression under these oxidative and genotoxic conditions was accompanied by a reduced formation of γ-H2AX foci and higher levels of total and phospho (Ser15) p53. Finally, ALDH3A1 was found to be localized both in the cytoplasm and the nucleus of transfected HCE-2 cells. Its cellular compartmentalization was not affected by oxidant treatment, while the mechanism by which ALDH3A1 translocates to the nucleus remains unknown. In conclusion, ALDH3A1 protects cells from both apoptosis and DNA damage by interacting with key homeostatic mechanisms associated with cellular morphology, cell cycle, and DDR.https://www.mdpi.com/1422-0067/24/6/5845aldehyde dehydrogenase 3A1corneacorneal epitheliumcorneal homeostasisantioxidantoxidative stress |
| spellingShingle | Georgia-Persephoni Voulgaridou Vasileios Theologidis Maria Venetikidou Ilias Tsochantaridis Avgi Tsolou Maria Koffa Mihalis I. Panayiotidis Aglaia Pappa Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells International Journal of Molecular Sciences aldehyde dehydrogenase 3A1 cornea corneal epithelium corneal homeostasis antioxidant oxidative stress |
| title | Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells |
| title_full | Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells |
| title_fullStr | Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells |
| title_full_unstemmed | Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells |
| title_short | Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells |
| title_sort | investigating the functional roles of aldehyde dehydrogenase 3a1 in human corneal epithelial cells |
| topic | aldehyde dehydrogenase 3A1 cornea corneal epithelium corneal homeostasis antioxidant oxidative stress |
| url | https://www.mdpi.com/1422-0067/24/6/5845 |
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