Study of the relationship between AGEs and oxidative stress damage to trophoblast cell mitochondria
Abstract
Objectives: To study the influence of AGEs on placental trophoblast mitochondria oxidative stress, and to explore the possible pathogenesis which may participate in pre-eclampsia.
Material and methods: Human trophoblast cells from early pregnancy were cultured by an enzyme-digestion method. When trophoblast cells reached approximately 70–80% after passages, they were incubated with pre-eclampsia serum for 24 hours. A fluorescent dye assay was applied to measure the mitochondrial membrane potential; ELISA was used to measure the activity of the mitochondrial permeability transition pore. mtDNA was detected by Real-time fluorescence quantitative Reverse Transcription-Polymerase Chain Reaction (RT-PCR). We continued to culture one group of cells with pre-eclampsia maternal serum, and other cells were pulsed with 600 mg/L AGEs. Cells were incubated for 16 hours before assaying the levels of mitochondrial oxidative stress damage.
Results: The levels of mitochondria oxidative stress damage in the AGEs group were higher than in the pre-eclampsia group 1 and pre-eclampsia group 2. There was no statistically significant difference in mitochondrial oxidative stress damage between the pre-eclampsia group 1 and group 2.
Conclusions: The AGEs are involved in the pathogenesis of pre-eclampsia, possibly through the enhancement of mitochondrial oxidative stress damage.
Keywords: pre-eclampsiaadvanced glycation end productsoxidative stresstrophoblast cell
References
- Chekir C, Nakatsuka M, Noguchi S, et al. Accumulation of advanced glycation end products in women with preeclampsia: possible involvement of placental oxidative and nitrative stress. Placenta. 2006; 27(2-3): 225–233.
- Remor AP, de Matos FJ, Ghisoni K, et al. Differential effects of insulin on peripheral diabetes-related changes in mitochondrial bioenergetics: involvement of advanced glycosylated end products. Biochim Biophys Acta. 2011; 1812(11): 1460–1471.
- Yoshimaru T, Suzuki Y, Inoue T, et al. Extracellular superoxide released from mitochondria mediates mast cell death by advanced glycation end products. Biochim Biophys Acta. 2008; 1783(12): 2332–2343.
- Zusterzeel PL, Rütten H, Roelofs HM, et al. Protein carbonyls in decidua and placenta of pre-eclamptic women as markers for oxidative stress. Placenta. 2001; 22(2-3): 213–219.
- Leveno KJ, Cunningham FG, Gant NF. Williams manual of obstetrics, 21st edition. McGraw-Hill 2003.
- Bierhaus A, Illmer T, Kasper M, et al. Advanced glycation end product (AGE)-mediated induction of tissue factor in cultured endothelial cells is dependent on RAGE. Circulation. 1997; 96(7): 2262–2271.
- Liu HP, Wang RG, Li CM. Establishment of in vitro culture system of human archae-generation trophoblasts. Practical Preventive Medicine. 2006; 13(5): 1109–1111.
- Cha KY, Lee SH, Chung HM, et al. Quantification of mitochondrial DNA using real-time polymerase chain reaction in patients with premature ovarian failure. Fertil Steril. 2005; 84(6): 1712–1718.
- Oliver EA, Buhimschi CS, Dulay AT, et al. Activation of the receptor for advanced glycation end products system in women with severe preeclampsia. J Clin Endocrinol Metab. 2011; 96(3): 689–698.
- Guedes-Martins L, Matos L, Soares A, et al. AGEs, contributors to placental bed vascular changes leading to preeclampsia. Free Radic Res. 2013; 47 Suppl 1: 70–80.
- Loor G, Kondapalli J, Iwase H, et al. Mitochondrial oxidant stress triggers cell death in simulated ischemia-reperfusion. Biochim Biophys Acta. 2011; 1813(7): 1382–1394.
- Fang XY, Li YG, Lin NY. Mitochondrial permeability transition pore and its mechanism of influence by the mitochondrial ATP-sensitive potassium channel opening. Journal of Shantou University Medical College. 2012; 25(1): 61–64.
- Yan Jy, Xu X. [Relationships between concentrations of free fatty acid in serum and oxidative-damage levels in placental mitochondria and preeclampsia]. Zhonghua Fu Chan Ke Za Zhi. 2012; 47(6): 412–417.
- Yu SY, Huang L, Song MB. Increased reactive oxygen species in endothelial cells stimulated by advanced glycation end products mediated by NADPH oxidase. Chinese Journal of Arteriosclerosis. 2008; 16(11): 857–860.
- Huang QT, Zhang M, Zhong M, et al. Advanced glycation end products as an upstream molecule triggers ROS-induced sFlt-1 production in extravillous trophoblasts: a novel bridge between oxidative stress and preeclampsia. Placenta. 2013; 34(12): 1177–1182.
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