TY - JOUR
T1 - Carotenoid derived aldehydes-induced oxidative stress causes apoptotic cell death in human retinal pigment epithelial cells
AU - Kalariya, Nilesh M.
AU - Ramana, Kota V.
AU - Srivastava, Satish K.
AU - van Kuijk, Frederik J.G.M.
N1 - Funding Information:
This work was supported by National Institutes of Health (NIH) Grants GM71036 (to K.V.R.), DK36118 (to S.K.S.) and Wilkins AMD Fund (to F.J.G.M.vK.).
PY - 2008/1
Y1 - 2008/1
N2 - 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.
AB - 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.
KW - age-related macular degeneration
KW - aldehydes
KW - antioxidants
KW - carotenoid
KW - oxidative stress
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UR - http://www.scopus.com/inward/citedby.url?scp=36749049202&partnerID=8YFLogxK
U2 - 10.1016/j.exer.2007.09.010
DO - 10.1016/j.exer.2007.09.010
M3 - Article
C2 - 17977529
AN - SCOPUS:36749049202
SN - 0014-4835
VL - 86
SP - 70
EP - 80
JO - Experimental Eye Research
JF - Experimental Eye Research
IS - 1
ER -