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

Department of Ophthalmology and Visual Sciences, University of Texas Medical Branch, Room 2.100, 700 University Boulevard, Galveston, TX 77555-1106, USA.
Experimental Eye Research (Impact Factor: 3.02). 02/2008; 86(1):70-80. DOI: 10.1016/j.exer.2007.09.010
Source: PubMed

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 beta-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-kappaB 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-kappaB 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.

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    • "Some of those products are involved in plant defense or architecture (Gomez-Roldan et al., 2008; Tsuchiya et al., 2010; Dor et al., 2011). In animals, ROSinduced oxidized carotenoid derivatives have been reported to be biologically active, playing a role in enzyme inhibition, changes in gene expression, transcription activation, or apoptosis (Siems et al., 2000; Sharoni et al., 2004; Kuntz et al., 2006; Lindshield et al., 2007; Kalariya et al., 2008). Although a signaling function of oxidized carotenoids has not been reported Figure 10. "
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    Plant physiology 03/2012; 158(3):1267-78. DOI:10.1104/pp.111.182394 · 7.39 Impact Factor
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    • "The serum starved RAW cells were washed with PBS and incubated with LPS without or with Benfotamine for 4 h. MMP was determined essentially as described by us earlier [31]. "
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    Free Radical Biology and Medicine 02/2010; 48(10):1423-34. DOI:10.1016/j.freeradbiomed.2010.02.031 · 5.71 Impact Factor
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    • "They observed lower lutein and zeaxanthin concentrations in the peripheral retina of autopsy eyes from persons with AMD, relative to controls, suggesting that pathology in the central macular did not explain their finding that AMD eyes have significantly less macular pigment than healthy eyes (Bone et al., 2001). It has been suggested that metabolism of lutein and zeaxanthin into various secondary products may account for the changes in MPOD in AMD (Kalariya, et al., 2008). This hypothesis is not widely accepted and requires further investigation. "
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    Vision research 10/2009; 50(7):716-28. DOI:10.1016/j.visres.2009.10.014 · 2.38 Impact Factor
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