Abstract
Objective
Alpha hemoglobin-stabilizing protein (AHSP) inhibits the production of reactive oxygen species in various cells, including erythrocytes. Reduced AHSP can mean reduced protection from stressors. Our objective was to investigate whether AHSP is involved in the response to stress in pregnancy.
Study design
Placentas were collected from normal term pregnancies (n = 10) and pregnancies complicated by HELLP (n = 10), intrauterine growth restriction (IUGR; n = 10) or fetal death (IUFD; n = 6). AHSP messenger RNA (mRNA) and protein were determined using real time quantitative polymerase chain reaction (PCR) and Western blot, respectively. All statistical analyses were performed by using the GraphPad Prism Software. Differences were considered significant at p < 0.05.
Results
Placental AHSP mRNA level in HELLP (4.16E10−4 ± 1.77) and IUFD (4.19E10−4 ± 3.37) were significantly decreased compared with controls (28.47E10−4 ± 14.86; p < 0.01), whereas levels in the IUGR group (7.55E10−4 ± 6.4) showed a trend toward being lower but the difference did not reach statistical significance. Western blot analysis results indicate a no significant increase of ASHP protein in the HELLP syndrome group and a significant decrease in the IUFD group compared with controls. There was no significant difference between the IUGR and control groups.
Conclusion
ASHP mRNA expression in the placenta is decreased in complicated pregnancies, and it may be involved in the pathogenic mechanisms leading to the adverse pregnancy outcome.
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References
al-Eissa YA, Ba’Aqeel HS, Haque KN, AboBakr AM, al-Kharfy TM, Khashoggi TY, al-Husain MA (1995) Determinants of term intrauterine growth retardation: the Saudi experience. Am J Perinatol 12:278–281
Betten A, Dahlgren C, Mellqvist UH, Hermodsson S, Hellstrand K (2004) Oxygen radical-induced natural killer cell dysfunction: role of myeloperoxidase and regulation by serotonin. J Leukoc Biol 75:1111–1115
Chen G, Wilson R, Cumming G, Walker JJ, Smith WE, McKillop JH (1994) Intracellular and extracellular antioxidant buffering levels in erythrocytes from pregnancy-induced hypertension. J Hum Hypertens 8:37–42
Cunningham FG, Lowe T, Guss S, Mason R (1985) Erythrocyte morphology in women with severe preeclampsia and eclampsia. Preliminary observations with scanning electron microscopy. Am J Obstet Gynecol 153:358–363
Dos Santos CO, Costa FF (2005) ASHP and beta-thalassemia: a possible genetic modifier. Hematology 10:157–161
Ferns G, Shams S, Shafi S (2006) Heat shock protein 27: its potential role in vascular disease. Int J Exp Pathol 87:253–274
Gareskog M, Eriksson UJ, Wentzel P (2006) Combined supplementation of folic acid and vitamin E diminishes diabetes-induced embryotoxicity in rats. Birth Defects Res A Clin Mol Teratol 76:483–490
Garzetti GG, Tranquilli AL, Cugini AM, Mazzanti L, Cester N, Romanini C (1993) Altered lipid composition, increased lipid peroxidation, and altered fluidity of the membrane as evidence of platelet damage in preeclampsia. Obstet Gynecol 81:337–340
Gell D, Kong Y, Eaton SA, Weiss MJ, Mackay JP (2002) Biophysical characterization of the alpha-globulin binding protein ASPH. J Biol Chem 277:40602–40609
Herrmann W, Hubner U, Koch I, Obeid R, Retzke U, Geisel J (2004) Alteration of homocysteine catabolism in pre-eclampsia, HELLP syndrome and placental insufficiency. Clin Chem Lab Med 42:1109–1111
Kaul DK, Liu XD, Chang HY, Nagel RL, Fabry ME (2004) Effect of fetal hemoglobin on microvascular regulation in sickle transgenic-knockout mice. J Clin Invest 114:1136–1145
Kihm AJ, Kong W, Russel JE et al (2002) An abundant erythroid protein that stabilizes free alpha-hemoglobin. Nature 417:758–763
Kong Y, Katein AM, Louden CS, Weiss MJ (2003) Loss of alpha hemoglobin stabilizing protein exacerbates thalassemia phenotypes in mice. Blood 102:46a
Miele G, Manson J, Clinton M (2001) A novel erythroid-specific marker of transmissible spongiform encephalopathies. Nat Med 7:361–364
Myatt L (2006) Placental adaptive responses and fetal programming. J Physiol 572:25–30
Papp E, Nardai G, Soti C, Csermely P (2003) Molecular chaperones, stress proteins and redox homeostasis. Biofactors 17:249–257
Rehberg JF, Briery CM, Hudson WT, Bofill JA, Martin JN (2006) Thrombotic thrombocytopenic purpura masquerading as hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome in late pregnancy. Obstet Gynecol 108:817–820
Rodgers GM, Taylor RN, Roberts GM (1988) Preeclampsia is associated with a serum factor cytotoxic to human endothelial cells. Am J Obstet Gynecol 159:908–914
Spickett CM, Reglinski J, Smith WE, Wilson R, Walker JJ, McKillop J (1998) Erythrocyte glutathione balance and membrane stability during preeclampsia. Free Radic Biol Med 24:1049–1055
Uotila JT, Tuimala RJ, Aarnio TM, Pyykkö KA, Ahotupa MO (1993) Findings on lipid peroxidation and antioxidant function in hypertensive complications of pregnancy. Br J Obstet Gynaecol 100:270–276
Walsh SW, Wang Y (1993) Deficient glutathione peroxidase activity in preeclampsia is associated with increased placental production of thromboxane and lipid peroxides. Am J Obstet Gynecol 169:1456–1461
Wang G, Guo X, Floros J (2005) Differences in the translation efficiency and mRNA stability mediated by 5′-UTR splice variants of human SP-A1 and SP-A2 genes. Am J Physiol Lung Cell Mol Physiol 289:497–508
Wisdom SJ, Wilson SR, McKillop JH, Walker JJ (1991) Antioxidant systems in normal pregnancy and pregnancy-induced hypertension. Am J Obstet Gynecol 165:1701–1704
Acknowledgment
We are indebted to Dr. Mitchell Weiss (Children’s Hospital of Philadelphia) for providing AHSP antibody. This work was supported by the Italian Ministry for University and Scientific Research through PRIN 2004-068971-007.
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Monica Emanuelli and Davide Sartini contributed equally to this paper.
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Emanuelli, M., Sartini, D., Rossi, V. et al. Alpha-hemoglobin-stabilizing protein (AHSP) in hemolysis, elevated liver enzyme, and low platelet (HELLP) syndrome, intrauterine growth restriction (IUGR) and fetal death. Cell Stress and Chaperones 13, 67–71 (2008). https://doi.org/10.1007/s12192-008-0009-5
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DOI: https://doi.org/10.1007/s12192-008-0009-5