Induction of oxidative and nitrosative stresses in human retinal pigment epithelial cells by all-trans-retinal

Journal Article · Sat Oct 15 04:00:00 EDT 2016 · Experimental Cell Research

DOI:https://doi.org/10.1016/J.YEXCR.2016.09.002· OSTI ID:22649773

Zhu, Xue ^[1]; Wang, Ke ^[1]; Zhang, Kai ^[1]; Zhou, Fanfan ^[2]; Zhu, Ling ^[3]

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1. Key Laboratory of Nuclear Medicine, Ministry of Health, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, Jiangsu Province (China)
2. Faculty of Pharmacy, University of Sydney, New South Wales 2006 (Australia)
3. Save Sight Institute, University of Sydney, New South Wales 2000 (Australia)

Delayed clearance of free form all-trans-retinal (atRAL) is estimated be the key cause of retinal pigment epithelium (RPE) cells injury during the pathogenesis of retinopathies such as age-related macular degeneration (AMD), however, the underlying molecular mechanisms are far from clear. In this study, we investigated the cytotoxicity effect and underlying molecular mechanism of atRAL on human retinal pigment epithelium ARPE-19 cells. The results indicated that atRAL could cause cell dysfunction by inducing oxidative and nitrosative stresses in ARPE-19 cells. The oxidative stress induced by atRAL was mediated through up-regulation of reactive oxygen species (ROS) generation, activating mitochondrial-dependent and MAPKs signaling pathways, and finally resulting in apoptosis of ARPE-19 cells. The NADPH oxidase inhibitor apocynin could partly attenuated ROS generation, indicating that NADPH oxidase activity was involved in atRAL-induced oxidative stress in ARPE-19 cells. The nitrosative stress induced by atRAL was mainly reflected in increasing nitric oxide (NO) production, enhancing iNOS, ICAM-1 and VCAM-1 expressions, and promoting monocyte adhesion. Furthermore, above effects could be dramatically blocked by using a nuclear factor kappa B (NF-κB) inhibitor SN50, indicated that atRAL-induced oxidative and nitrosative stresses were mediated by NF-κB. The results provide better understanding of atRAL-induced toxicity in human RPE cells. - Highlights: • atRAL induces oxidative stress-mediated apoptosis in ARPE-19 cells. • atRAL induces oxidative stress-mediated inflammation in ARPE-19 cells. • NF-κB is involved in atRAL-induced oxidative and nitrosative stresses.

• OSTI ID: 22649773
• Journal Information: Experimental Cell Research, Journal Name: Experimental Cell Research Journal Issue: 1 Vol. 348; ISSN 0014-4827; ISSN ECREAL
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
APOPTOSIS
CLEARANCE
EPITHELIUM
INDUCTION
INFLAMMATION
INJURIES
MITOCHONDRIA
MONOCYTES
NITRIC OXIDE
OXIDASES
OXIDATION
PATHOGENESIS
RHODOPSIN
STRESSES
TOXICITY