Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells

Nilesh M. Kalariya, Kota Ramana, Satish Srivastava, Frederik J G M van Kuijk

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Carotenoids have been advocated as potential therapeutic agents in treating age-related macular degeneration (AMD). In ocular tissues carotenoids may undergo oxidation and form carotenoid-derived aldehydes (CDA), which would be toxic to tissues. We have investigated the cytotoxic effects of CDA from β-carotene, Lutein and Zeaxanthin on human retinal pigment epithelial cells (ARPE-19). The serum-starved ARPE-19 cells were treated with CDA without or with antioxidant, N-acetylcysteine (NAC) and cell viability, apoptosis, reactive oxygen species (ROS) levels, nuclear chromatin condensation as well as fragmentation, change in mitochondrial membrane potential (MMP) and activation of transcription factors NF-κB and AP-1 were determined. We observed a dose and time-dependent decline in cell viability upon incubation of ARPE-19 cells with CDA. The CDA treatment also led to elevation in ROS levels in a dose-dependent manner. Upon CDA treatment a significant number of apoptotic cells were observed. Also early apoptotic changes in ARPE-19 cells induced by CDA were associated with change in MMP. Increased nuclear chromatin condensation and fragmentation were also observed in cells treated with CDA. The cytotoxicity of CDA in ARPE-19 cells was significantly ameliorated by the antioxidant, NAC. Furthermore, CDA induced the activation of NF-κB and AP-1 which was significantly inhibited by NAC. Thus our results demonstrate that CDA could increase the oxidative stress in ARPE-19 cells by elevating ROS levels that would cause imbalance in cellular redox status, which could lead to cell death. This would suggest that high carotenoid supplementation for treatment of AMD should be used cautiously.

Original languageEnglish (US)
Pages (from-to)70-80
Number of pages11
JournalExperimental Eye Research
Volume86
Issue number1
DOIs
StatePublished - Jan 2008

Fingerprint

Retinal Pigments
Carotenoids
Aldehydes
Oxidative Stress
Cell Death
Epithelial Cells
Acetylcysteine
Reactive Oxygen Species
Mitochondrial Membrane Potential
Transcription Factor AP-1
Macular Degeneration
Chromatin
Cell Survival
Antioxidants
Lutein
Poisons
Oxidation-Reduction

Keywords

  • age-related macular degeneration
  • aldehydes
  • antioxidants
  • carotenoid
  • oxidative stress

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems

Cite this

Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells. / Kalariya, Nilesh M.; Ramana, Kota; Srivastava, Satish; van Kuijk, Frederik J G M.

In: Experimental Eye Research, Vol. 86, No. 1, 01.2008, p. 70-80.

Research output: Contribution to journalArticle

Kalariya, Nilesh M. ; Ramana, Kota ; Srivastava, Satish ; van Kuijk, Frederik J G M. / Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells. In: Experimental Eye Research. 2008 ; Vol. 86, No. 1. pp. 70-80.
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