The oxidant role of 4-hydroxynonenal in corneal epithelium.

Longlong Chen,Zuguo Liu,Jing Zhou,Rongrong Zong,Tong Zhou,Yueping Zhou,Lianping Ge,Jian-Xing Ma

doi:10.1038/srep10630

Abstract

4-Hydroxynonenal (4-HNE or HNE) is a main endogenous product of cellular lipid peroxidation in tissues and is reported to play pathogenic roles in eye diseases. Here we investigated the association between 4-HNE and oxidative stress in the corneal epithelium. 4-HNE suppressed the cell viability of human corneal epithelial cells (HCE) in a concentration dependent manner. 4-HNE significantly increased the level of 3-Nitrotyrosine (3-NT), a marker of oxidative stress, in HCE cells and corneal epithelium of rats by immunofluorescent staining and Western blot analysis. To its underlying mechanistic on ROS system, 4-HNE elevated the ROS generation enzyme NADPH oxidase 4 (NOX4) and induced the activation of NF-E2–related factor-2 (NRF2) and its downstream effectors: NAD(P)H dehydrogenase (quinone 1) (NQO1) and glutathione S-transferase P (GSTP). Furthermore, N-acetylcysteine (NAC), an antioxidant and ROS scavenger, antagonized the inhibitory and oxidant effects of 4-HNE on the corneal epithelial cells. In conclusion, 4-HNE plays an oxidant role in the corneal epithelium and this work provides a new strategy for the pathogenesis and treatment of corneal diseases.

Highlights

Oxidative stress refers to an imbalance between oxidation and antioxidation in the cells, which is considered to be an important factor leading to aging and diseases
These results suggested that 4-HNE plays oxidant role in the corneal epithelium through upregulating the reactive oxygen species (ROS) generation
We provided novel evidence that 4-Hydroxynonenal serves as an inducer to oxidative stress in the corneal epithelium via regulating the reactive oxygen species (ROS) system

Summary

Introduction

Oxidative stress refers to an imbalance between oxidation and antioxidation in the cells, which is considered to be an important factor leading to aging and diseases. Ocular surface diseases, including granular corneal dystrophy, atopic keratoconjunctivitis, pterygium, and dry eye[9,10,11,12], as well as cataract[13], age related macular degeneration (AMD)[14] and diabetic retinopathy[15], while the role and the underlying mechanism of 4-HNE in the eyes remain largely unknown. The aim of this present study was to focus on and investigate the association between 4-HNE and oxidative stress in the corneal epithelium and explore the underlying mechanistic

Objectives

Methods

Findings

Conclusion