Rafael Bueno Orcy

Signalization of Akt/PKB in the Placenta, Skeletal Muscle and Adipose Tissue of Preeclampsia Patients

Preeclampsia (PE) is a significant cause of fetal and maternal mortality around the world and there is evidence that insulin resistance has been implicated in the pathophysiology of PE. The Akt/PKB pathway is stimulated by insulin and performs several vital functions relative to growth, survival and cellular metabolism. Objective: To investigate the basal expression of Akt/PKB, HSP90 expression, proteins that regulate Akt/PKB activity and substrate in the placenta, skeletal muscle and adipocytes of normal and PE parturient. Method: Samples were collected from 17 normal patients and 17 PE patients, and analyzed by Western blot to quantify the protein expression involved in signaling cascade of Akt/PKB. Results: Total Akt/PKB expression for normal placentas was 1.85 (1.07–3.12) and 1.53 (1.27–3.08) in PE (p = 1.00); in the adipose tissue of normal placentas it was 1.10 (0.53–1.73) and 1.66 (0.83–2.00) in PE (p = 0.37). Conclusions: There was no difference in the Akt/PKB pathway, in basal state, in placentas and skeletal muscle of normal and PE patients. However, defects in this signaling pathway as pathophysiology of PE cannot be excluded because it is necessary to analyze this pathway during stimulation.

Insulin stimulation of Akt/PKB phosphorylation in the placenta of preeclampsia patients

CONTEXT AND OBJECTIVE Preeclampsia is a multi-systemic disease and one of the most frequent severe health problems during pregnancy. Binding of insulin triggers phosphorylation and activates cytoplasmic substrates such as phosphatidylinositol 3 kinase (PI3K). Phosphorylation of membrane phosphoinositide 2 (PIP2) to phosphoinositide 3 (PIP3) by PI3K starts Akt/PKB activation. Defects in phosphorylation of the insulin receptor and its substrates have an important role in insulin resistance. Studies have shown that insulin resistance is associated with preeclampsia and its pathophysiology. The aim here was to investigate insulin stimulation of the Akt/PKB pathway in the placenta, in normal and preeclampsia parturients. DESIGN AND SETTING Cross-sectional study in a tertiary public university hospital. METHODS Placentas were collected from 12 normal and 12 preeclampsia patients. These were stimulated and analyzed using Western blot to quantify the Akt/PKB phosphorylation. RESULTS The insulin stimulation was confirmed through comparing the stimulated group (1.14 ± 0.10) with the non-stimulated group (0.91 ± 0.08; P < 0.001). The phosphorylation of Akt/PKB did not differ between the placenta of the normal patients (1.26 ± 0.16) and those of the preeclampsia patients (1.01 ± 0.11; P = 0.237). CONCLUSIONS In vitro insulin stimulation of the human placenta has been well established. There was no difference in Akt/PKB phosphorylation, after stimulation with insulin, between placentas of normal and preeclampsia patients. Nevertheless, it cannot be ruled out that the Akt/PKB signaling pathway may have a role in the pathophysiology of preeclampsia, since the substrates of Akt/PKB still need to be investigated.

Contents Vol. 66, 2008

M.A. Belfort, Provo, Utah J. Bornstein, Nahariya H.L. Brown, Durham, N.C. C. Chapron, Paris P.G. Crosignani, Milan J. de Haan, Maastricht G.A. Dekker, Adelaide J.A. Deprest, Leuven K. Hecher, Hamburg S. Kahhale, São Paulo H. Kliman, New Haven, Conn. T.F. Kruger, Tygerberg J.A. Kuller, Raleigh, N.C. M.J. Kupferminc, Tel Aviv H. Minkoff , Brooklyn, N.Y. J. Moodley, Congella J.M. Mwenda, Nairobi H. Odendaal, Tygerberg J.T. Repke, Hershey, Pa. G.R. Saade, Galveston, Tex. Founded 1895 as ‘Monatsschrift für Geburtshilfe und Gynäkologie’, continued 1946–1969 as ‘Gynaecologia’ and 1970–1977 as ‘Gynecologic Investigation’