Padmini Ekambaram, Lavanya Srinivasan, Uthra Venkatraman
P.G. Department of Biochemistry, Bharathi Women's College, Affiliated to University of Madras, Chennai, Tamilnadu, India.
Clin Chem Lab Med. 2009;47(9):1073-80. doi: 10.1515/CCLM.2009.247.
Evidence is accumulating that mitochondrial (Mt) oxidative stress plays a role in the pathogenesis of preeclampsia. The current study analyzes the stress levels, energy status and associated enzymatic alteration in placental mitochondria of preeclamptic (n=30) and normotensive (n=35) subjects.
Total Mt stress was measured using dichlorofluorescin (DCFH) oxidant analysis, malondialdehyde (MDA) concentrations, protein carbonyl (PC) concentrations and measurement of nitrite (NO2(-)) and nitrate (NO3(-)). Activity of antioxidant enzymes including superoxide dismutase (SOD), glutathione peroxidase (GPx) and the glutathione redox ratio (GRR) were measured. The ATP/ADP (adenosine triphosphate/adenosine diphosphate) concentrations and respiratory chain enzyme activities were also analyzed. The expression of heat shock protein 70 (HSP70) was measured in mitochondria.
The DCFH oxidants, MDA, PC concentrations, and concentrations of NO2(-) and NO3(-) were significantly higher in the preeclamptic group (p<0.01) compared with the control group. The activities of SOD, GPx, GRR [glutathione (GSH)/glutathione disulfate (GSSG)] (p<0.01, p<0.001), ATP/ADP and respiratory chain enzyme activities were reduced significantly (p<0.001) in preeclamptic conditions. The placental mitochondrial HSP70 (mtHSP70) showed significant over expression in the preeclamptic group (p<0.001) compared with the control group.
These results provide the first line of evidence for accumulated Mt stress demonstrated by increased stress markers, decreased antioxidants and enhanced mtHSP70. The study illustrates the probable protective mechanism of mtHSP70 against the generated stress. This is primarily to combat the enzymatic and free radical mediated damage produced in preeclampsia.
越来越多的证据表明，线粒体（Mt）氧化应激在先兆子痫的发病机制中起作用。本研究分析了先兆子痫患者（n = 30）和血压正常者（n = 35）胎盘线粒体中的应激水平、能量状态及相关酶的变化。
使用二氯荧光素（DCFH）氧化剂分析、丙二醛（MDA）浓度、蛋白质羰基（PC）浓度以及亚硝酸盐（NO2(-)）和硝酸盐（NO3(-)）的测量来测定总Mt应激。测量抗氧化酶的活性，包括超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和谷胱甘肽氧化还原比（GRR）。还分析了三磷酸腺苷/二磷酸腺苷（ATP/ADP）浓度和呼吸链酶活性。测量线粒体中热休克蛋白70（HSP70）的表达。
与对照组相比，先兆子痫组的DCFH氧化剂、MDA、PC浓度以及NO2(-)和NO3(-)浓度显著更高（p<0.01）。在先兆子痫状态下，SOD、GPx、GRR[谷胱甘肽（GSH）/氧化型谷胱甘肽（GSSG）]的活性（p<0.01，p<0.001）、ATP/ADP和呼吸链酶活性显著降低（p<0.001）。与对照组相比，先兆子痫组胎盘线粒体HSP70（mtHSP70）显著过度表达（p<0.001）。
这些结果为Mt应激积累提供了首个证据，表现为应激标志物增加、抗氧化剂减少和mtHSP70增强。该研究阐明了mtHSP70对抗所产生应激的可能保护机制。这主要是为了对抗先兆子痫中由酶和自由基介导的损伤。
