Preeclamptic placental stress and over expression of mitochondrial HSP70

Abstract

Background: 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. Methods: 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. Results: 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. Conclusions: 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. Clin Chem Lab Med 2009;47:1073–80.