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  3. Aldehyde dehydrogenase 3A1 confers oxidative stress resistance accompanied by altered DNA damage response in human corneal epithelial cells

Aldehyde dehydrogenase 3A1 confers oxidative stress resistance accompanied by altered DNA damage response in human corneal epithelial cells

  • Free Radic Biol Med. 2020 Apr:150:66-74. doi: 10.1016/j.freeradbiomed.2020.01.183.
Georgia-Persephoni Voulgaridou 1,  Ilias Tsochantaridis 1,  Christos Tolkas 1,  Rodrigo Franco 2,  Alexandra Giatromanolaki 3,  Mihalis I Panayiotidis 4,  Aglaia Pappa 5
Affiliations

Affiliations

  • 1 Department of Molecular Biology & Genetics, Democritus University of Thrace, University Campus Dragana, 68100, Alexandroupolis, Greece.
  • 2 Redox Biology Center, 114 VBS 0905, University of Nebraska-Lincoln, Lincoln, NE, 68588, USA; School of Veterinary Medicine and Biomedical Sciences, University of Nebraska-Lincoln, Lincoln, NE, 68583, USA.
  • 3 Department of Pathology, Democritus University of Thrace, University General Hospital of Alexandroupolis, Alexandroupolis, Greece.
  • 4 Department of Electron Microscopy & Molecular Pathology, The Cyprus Institute of Neurology & Genetics, Nicosia, 2371, Cyprus.
  • 5 Department of Molecular Biology & Genetics, Democritus University of Thrace, University Campus Dragana, 68100, Alexandroupolis, Greece. Electronic address: [email protected].
PMID: 32006654 DOI: 10.1016/j.freeradbiomed.2020.01.183
Abstract

Aldehyde dehydrogenase 3A1 is constitutively expressed in a taxon-specific manner in the cornea, where, due to its high abundance, it has been characterized as a corneal crystallin. ALDH3A1 has been proposed to be a multifaceted protein that protects cellular homeostasis through several modes of action. The present study examines the mechanisms by which ALDH3A1 exerts its cytoprotective role under conditions of oxidative stress. To this end, we have utilized an isogenic HCE-2 (human corneal epithelium) cell line pair differing in the expression of ALDH3A1. Single cell gel electrophoresis assay and H2DCFDA analysis revealed that the expression of ALDH3A1 protected HCE-2 cells from H2O2-, tert-butyl peroxide- and etoposide-induced oxidative and genotoxic effects. Furthermore, comparative qPCR analysis revealed that a panel of cell cycle (Cyclins B1, B2, D, E), Apoptosis (p53, Bax, Bcl-2, Bcl-xL) and DNA damage response (DNA-PK, NBS1) genes were up-regulated in the ALDH3A1 expressing HCE-2 cells. Moreover, the expression profile of a variety of DNA damage signaling (DDS)-related genes, was investigated (under normal and oxidative stress conditions) by utilizing the RT2 profiler™ PCR array in both isogenic HCE-2 cell lines. Our results demonstrated that several genes associated with ATM/ATR signaling, cell cycle regulation, Apoptosis and DNA damage repair were differentially expressed under all conditions tested. In conclusion, this study suggests that ALDH3A1 significantly contributes to the antioxidant defense of corneal homeostasis by maintaining DNA integrity possibly through altering the expression of specific DDS-related genes. Further studies will shed light on the precise role(s) of this multifunctional protein.

Keywords

ALDH3A1; ALDHs; Aldehyde dehydrogenase 3A1; Antioxidant; Corneal homeostasis; DDR; DDS; DNA damage; DNA damage response; DNA damage signaling; Oxidative stress.

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