1.
Zinc Protects Oxidative Stress-Induced RPE Death by Reducing Mitochondrial Damage and Preventing Lysosome Rupture.
Rajapakse, D, Curtis, T, Chen, M, Xu, H
Oxidative medicine and cellular longevity. 2017;:6926485
Abstract
Zinc deficiency is known to increase the risk of the development of age-related macular degeneration (AMD), although the underlying mechanism remains poorly defined. In this study, we investigated the effect of zinc on retinal pigment epithelium (RPE) survival and function under oxidative conditions. Zinc level was 5.4 μM in normal culture conditions (DMEM/F12 with 10% FCS) and 1.5 μM in serum-free medium (DMEM/F12). Under serum-free culture conditions, the treatment of RPE cells with oxidized photoreceptor outer segment (oxPOS) significantly increased intracellular ROS production, reduced ATP production, and promoted RPE death compared to oxPOS-treated RPE under normal culture condition. Serum deprivation also reduced RPE phagocytosis of oxPOS and exacerbated oxidative insult-induced cathepsin B release from lysosome, an indicator of lysosome rupture. The addition of zinc in the serum-free culture system dose dependently reduced ROS production, recovered ATP production, and reduced oxidative stress- (oxPOS- or 4-HNE) induced cell death. Zinc supplementation also reduced oxidative stress-mediated cathepsin B release in RPE cells. Our results suggest that zinc deficiency sensitizes RPE cells to oxidative damage, and zinc supplementation protects RPE cells from oxidative stress-induced death by improving mitochondrial function and preventing lysosome rupture.
2.
Bioaccumulation and tolerance characteristics of a submerged plant (Ceratophyllum demersum L.) exposed to toxic metal lead.
Chen, M, Zhang, LL, Li, J, He, XJ, Cai, JC
Ecotoxicology and environmental safety. 2015;:313-21
Abstract
A hydroponic study was conducted to investigate the lead bioaccumulation and tolerance characteristics of Ceratophyllum demersum L. exposed to various lead concentrations (5-80 μM) for 7, 14 or 21 days. Lead accumulation increased with increasing concentrations of metal in the solution, to a maximum accumulation of 4016.4 mg kg(-1) dw. Unexpectedly, the release of accumulated lead from the plants into solution was observed for all experimental groups except those exposed to 5 μM. Both the biomass and protein content of the plants responded significantly to lead stress. Malondialdehyde (MDA) levels increased substantially at lead concentrations below 20 μM, further indicating that this metal is toxic to the plants. To reveal the mechanism underlying the defense against lead stress, plants were also assayed for the activities of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD), as well as other relevant enzymes such as phenylalanine ammonia-lyase (PAL) and polyphenol oxidase (PPO). The activities of both SOD and CAT increased at lower lead concentrations and with shorter exposure times, followed by a decline, but the activities of POD and its isoenzymes continued to increase under all conditions. Moreover, increases in the activities of PAL and PPO were observed only for the 14-day treatment, and these two enzymes were not sensitive to lead concentration. These results suggest that C. demersum exhibits strong tolerance within a specific concentration range of lead in solution; according to regression analysis, 40 μM is suggested to be this plant's tolerance threshold for lead in water. Furthermore, the malfunction of this tolerance mechanism might accelerate the metal-release process. These attributes are likely to be beneficial for utilizing C. demersum in phytoremediation applications.
3.
Protective efficacy of vitamins C and E on p,p'-DDT-induced cytotoxicity via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.
Jin, X, Song, L, Liu, X, Chen, M, Li, Z, Cheng, L, Ren, H
PloS one. 2014;(12):e113257
Abstract
Dichlorodiphenoxytrichloroethane (DDT) is a known persistent organic pollutant and liver damage toxicant. However, there has been little emphasis on the mechanism underlying liver damage toxicity of DDT and the relevant effective inhibitors. Hence, the present study was conducted to explore the protective effects of vitamin C (VC) and vitamin E (VE) on the cytotoxicity of DDT in HL-7702 cells and elaborate the specific molecular mechanisms. The results demonstrated that p,p'-DDT exposure at over 10 µM depleted cell viability of HL-7702 cells and led to cell apoptotic. p,p'-DDT treatment elevated the level of reactive oxygen species (ROS) generation, induced mitochondrial membrane potential, and released cytochrome c into the cytosol, with subsequent elevations of Bax and p53, along with suppression of Bcl-2. In addition, the activations of caspase-3 and -8 were triggered. Furthermore, p,p'-DDT promoted the expressions of NF-κB and FasL. When the cells were exposed to the NF-κB inhibitor (PDTC), the up-regulated expression of FasL was attenuated. Strikingly, these alterations caused by DDT treatment were prevented or reversed by the addition of VC or VE, and the protective effects of co-treatment with VC and VE were higher than the single supplement with p,p'-DDT. Taken together, these findings provide novel experimental evidences supporting that VC or/and VE could reduce p,p'-DDT-induced cytotoxicity of HL-7702 cells via the ROS-mediated mitochondrial pathway and NF-κB/FasL pathway.