Mitochondrial role in adaptive response to stress conditions in preeclampsia

Abstract

Preeclampsia (PE) is a pregnancy-specific syndrome, characterized in general by hypertension with proteinuria or other systemic disturbances. PE is the major cause of maternal and fetal morbidity and mortality worldwide. However, the etiology of PE still remains unclear. Our study involved 38 patients: 14 with uncomplicated pregnancy; 13 with early-onset PE (eoPE); and 11 with late-onset PE (loPE). We characterized the immunophenotype of cells isolated from the placenta and all biopsy samples were stained positive for Cytokeratin 7, SOX2, Nestin, Vimentin, and CD44. We obtained a significant increase in OPA1 mRNA and protein expression in the eoPE placentas. Moreover, TFAM expression was down-regulated in comparison to the control (p < 0.01). Mitochondrial DNA copy number in eoPE placentas was significantly higher than in samples from normal pregnancies. We observed an increase of maximum coupled state 3 respiration rate in mitochondria isolated from the placenta in the presence of complex I substrates in the eoPE group and an increase of P/O ratio, citrate synthase activity and decrease of Ca2+-induced depolarization rate in both PE groups. Our results suggest an essential role of mitochondrial activity changes in an adaptive response to the development of PE.

Glucose and lipid metabolism disorders in the chickens with dexamethasone‐induced oxidative stress

“…This work observed that the activity of CS in the liver increased with DEX treatment. The result is accorded with the report that OS could increase the activity of citrate synthase in mitochondria (Sheeran & Pepe, ; Vishnyakova et al., ). Also, citrate inhibits phosphofructokinase‐1 (the rate‐limiting enzyme of glycolysis).…”

Reduction of acute mild stress corticosterone response and changes in stress‐responsive gene expression in male Balb/c mice after repeated administration of a Rhodiola rosea L. root extract

“…Other genes were regulated by R. rosea HRE but their modulation depended more strongly on the brain structure considered. In the amygdala, the R. rosea HRE and acute mild stress interaction damped the expression of ND2, a mitochondrial membrane respiratory chain gene, suggesting an essential role of mitochondrial activity as an adaptive response to stress, as previously proposed (Vishnyakova et al, ). In the PFC, BHLHB2, a gene implicated in neurotrophic factor activity and neuronal excitability, was upregulated by R. rosea HRE, suggesting improved communication between neurons.…”

Metformin, the aspirin of the 21st century: its role in gestational diabetes mellitus, prevention of preeclampsia and cancer, and the promotion of longevity

“…Recently, Professor Gennady Sukhikh’s Research Institute in Moscow has reported the following findings, indicating that mitochondrial functional changes in the placenta occur in both early- and late-onset preeclampsia when compared to normal pregnancy(208):…”

“…This gene is involved in mitochondrial fusion and in the cristae structure of the inner mitochondrial membrane, a fine-tuned process crucial for mitochondrial quality control; 2) a five-fold decrease in the mitochondrial transcription factor (TFAM)-A; 3) a 1.5-fold increase of the relative placental mitochondrial DNA copy number; and 4) increased mitochondrial respiration in the presence of Complex I substrates(208). …”

“…Thus, early-onset preeclampsia is associated with mitochondrial activation, up-regulation of OPA-1, active DNA replication (resulting from a high respiration rate), and TFAM down-regulation, while both early and late preeclampsia are associated with an elevated P/O ratio(208). …”