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

被引：29

作者：

Voulgaridou, Georgia-Persephoni ^{[1
]}

Tsochantaridis, Ilias ^{[1
]}

Tolkas, Christos ^{[1
]}

Franco, Rodrigo ^{[2
,3
]}

Giatromanolaki, Alexandra ^{[4
]}

Panayiotidis, Mihalis, I ^{[5
]}

Pappa, Aglaia ^{[1
]}

机构：

[1] Democritus Univ Thrace, Dept Mol Biol & Genet, Univ Campus, Dragana 68100, Alexandroupolis, Greece

[2] Univ Nebraska Lincoln, Redox Biol Ctr, 114 VBS 0905, Lincoln, NE 68588 USA

[3] Univ Nebraska Lincoln, Sch Vet Med & Biomed Sci, Lincoln, NE 68583 USA

[4] Democritus Univ Thrace, Univ Gen Hosp Alexandroupolis, Dept Pathol, Alexandroupolis, Greece

[5] Cyprus Inst Neurol & Genet, Dept Electron Microscopy & Mol Pathol, CY-2371 Nicosia, Cyprus

来源：

FREE RADICAL BIOLOGY AND MEDICINE | 2020年 / 150卷

关键词：

ALDH3A1; Aldehyde dehydrogenase 3A1; ALDHs; Corneal homeostasis; DNA damage response; DDR; DNA damage signaling; DDS; Oxidative stress; DNA damage; Antioxidant; MOLECULAR-MECHANISMS; GENE-EXPRESSION; MULTIPLE FUNCTIONS; HYDROGEN-PEROXIDE; ALDH3A1; CYCLE; ENDONUCLEASE; LOCALIZATION; BINDING; SINGLE;

D O I：

10.1016/j.freeradbiomed.2020.01.183

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 (TM) 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.

引用

页码：66 / 74

页数：9

共 39 条

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