Investigating the Functional Roles of Aldehyde Dehydrogenase 3A1 in Human Corneal Epithelial Cells

• Published in: International journal of molecular sciences Vol. 24; no. 6; p. 5845
• Main Authors: Voulgaridou, Georgia-Persephoni, Theologidis, Vasileios, Venetikidou, Maria, Tsochantaridis, Ilias, Tsolou, Avgi, Koffa, Maria, Panayiotidis, Mihalis I, Pappa, Aglaia
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 01-03-2023; MDPI
• Subjects: Aldehyde dehydrogenase; Aldehyde Dehydrogenase - genetics; Aldehyde Dehydrogenase - metabolism; aldehyde dehydrogenase 3A1; Aldehydes; antioxidant; Antioxidants; Apoptosis; Carboxylic acids; Cell cycle; Cell proliferation; Cornea; Cornea - metabolism; corneal epithelium; corneal homeostasis; Cytology; Cytoplasm; Cytotoxicity; Dehydrogenases; DNA damage; E-cadherin; Epithelial cells; Epithelial Cells - metabolism; Epithelium; Etoposide; Flow cytometry; Genotoxicity; Humans; Hydrogen peroxide; Hydrogen Peroxide - metabolism; Hydrogen Peroxide - pharmacology; Investigations; Molecular modelling; Morphology; Nuclei (cytology); Oxidants; Oxidative stress; Oxidizing agents; p53 Protein; Proteins; Tumor proteins; Wound healing; United Kingdom; Germany; antioxidant; wound healing; DNA damage response; cornea; DNA damage; aldehyde dehydrogenase 3A1; nuclear localization; cell cycle regulation; corneal homeostasis; corneal epithelium; oxidative stress
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms24065845

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
. Similarly, the ALDH3A1/HCE-2 cells demonstrated higher mobility, reduced proliferation, upregulation of
and downregulation of
and
. 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
O
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.