Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage

  • Maria Ekawati Biomedical Sciences Doctoral Program Study, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Ninik Mujihartini Center of Hypoxia and Oxydative Stress Study, Departement of Biochemistry and Molecular Biology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Ahmad A. Jusuf Department of Histology, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Nani Dharmasetiawani Department of Child Health, Budi Kemuliaan Women and Children Hospital, Jakarta
  • Sri W.A. Jusman Department of Biochemistry and Biology Molecular, Faculty of Medicine, Universitas Indonesia, Jakarta
  • Mohamad Sadikin Department of Biochemistry and Biology Molecular, Faculty of Medicine, Universitas Indonesia, Jakarta
Keywords: endothelial junction protein, intraventricular hemorrhage, hypoxia, oxidative stress
Abstract viewed: 1516 times
PDF downloaded: 550 times

Abstract

Background: Placental hypoxia may lead to oxidative stress, which inflicts damage to capillary protein junction. The aim of this study was to evaluate altered expression of endothelial junction protein of capillaries in hypoxia condition and to observe its correlation with the incidence of  intraventricular hemorrhage in premature infants.

Methods: A cross-sectional study was conducted by using placental tissues of premature infants as amodel of capillary integrity (29 hypoxic and 29 non-hypoxic). Hypoxia inducible factor (HIF)-1α was measured to define placental tissue response to hypoxia; malondialdehyde (MDA) and glutathione (GSH) served as markers of oxidative stress. The expressions of junctional proteins, N-cadherin and occludin were analyzed by immunohistochemistry. Intraventricular hemorrhage (IVH) was detected by cranial ultrasound at the third day. Unpaired t test, Mann-Whitney, and Chi-square tests were used to analyze the data.

Results: The HIF-1α and MDA levels were slightly, but not significantly, higher in hypoxia group {13.64±8.70 pg/mg protein and 10.31 pmol/mg tissue (ranged 1.92–93.61), respectively}  compared to non- hypoxia group {10.65±5.35 pg/mg protein and 9.77 pmol/mg tissue (ranged 2.42–93.31)}. GSH levels were not different in both groups (38.14 (ranged 9.44–118.91) and  38.47(ranged 16.49–126.76) ng/mg protein, respectively. mRNA expression of N-cadherin (0.13) and occludin (0.096) were significantly lower in hypoxia comparedto non-hypoxia group (p=0,001), while protein expression of  N-cadherin (3.4; 75.9; 6.9; 13.8%) and occludin  (20.7; 3.4; 69.0; 3.4; 6.9%)  in hypoxia group was not associated with IVH (p=0.783 and p=0.743).

Conclusion: Hypoxia altered expression of endothelial junction protein in placental capillaries, but no association with intraventricular hemorrhage was observed.

References

  1. Belkacemi L, Nelson DM, Desai M, Ross MG. Maternal undernutrition and fetal programming: role of the placenta. In: Kay HH, Nelson DM, Wang Y, editors. The Placenta. Oxford, UK:Wiley-Blackwell; 2011. p. 1–15. http://dx.doi.org/10.1002/9781444393927.ch1

  2. Frank HG. Placenta and Intrauterine Environment. In : Polin RA, Fox WW, Abman SH, editors. Fetal and Neonatal Physiology. 4th ed. Philadelphia. Elsevier Saunders. 2011; p. 108–20. http://dx.doi.org/10.1016/B978-1-4160-3479-7.10011-4

  3. Stolp H, Neuhaus A, Sundramoorthi R, Molnár Z. The long and the short of it: gene and environment interactions during early cortical development and consequences for long-term neurological disease. Front Psychiatry. 2012;3(50):1–22. http://dx.doi.org/10.3389/fpsyt.2012.00050

  4. Bazzoni G, Dejana E. Endothelial cell-to-cell junctions: molecular organization and role in vascular homeostasis. Physiol Rev. 2004;84(3):869–901. http://dx.doi.org/10.1152/physrev.00035.2003

  5. Ballabh P, Braun A, Nedergaard M. The blood-brain barrier: an overview: structure, regulation, and clinical implications. Neurobiol Dis. 2004;16(1):1–13. http://dx.doi.org/10.1016/j.nbd.2003.12.016

  6. González-Mariscal L, Tapia R, Chamorro D. Crosstalk of tight junction components with signaling pathways. Biochim Biophys Acta. 2008;1778(3):729–56. http://dx.doi.org/10.1016/j.bbamem.2007.08.018

  7. Dejana E, Tournier-Lasserve E, Weinstein BM. The control of vascular integrity by endothelial cell junctions: molecular basis and pathological implications. Dev Cell. 2009;16(2):209–21. http://dx.doi.org/10.1016/j.devcel.2009.01.004

  8. Halliwell B, Gutteridge JMC. Free radicals in biology and medicine. 4th ed. New York: Oxf Univ Press; 2007. p.30–337.

  9. Escobar J, Cernada M, Vento M. Oxygen and oxydative stress in the neonatal period. NeoReviews. 2011;12(11):613–24. http://dx.doi.org/10.1542/neo.12-11-e613

  10. Lata H, Ahuja GK, Narang APS, Walia L. Effect of immobilisation stress on lipid peroxidation and lipid profile in rabbits. Indian J Clin Biochem. 2004;19(2):1–4. http://dx.doi.org/10.1007/BF02894248

  11. Ayala A, Mu-oz MF, Argüelles S. Lipid peroxidation: production, metabolism, and signaling mechanisms of malondialdehyde and 4-hydroxy-2-nonenal. Oxid Med Cell Longev. 2014;2014:1–31. http://dx.doi.org/10.1155/2014/360438

  12. Zhang DX, Gutterman DD. Mitochondrial reactive oxygen species-mediated signaling in endothelial cells. Am J Physiol Heart Circ Physiol. 2007;292(5):H2023–31. http://dx.doi.org/10.1152/ajpheart.01283.2006

  13. Wang Y, Lewis DF, Alexander JS, Granger DN. Endothelial barrier function in preeclampsia. Front Biosci. 2007;12:2412–24.http://dx.doi.org/10.2741/2243

  14. Trollmann R, Strasser K, Keller S, Antoniou X, Grenacher B, Ogunshola OO, et al. Placental HIFs as markers of cerebral hypoxic distress in fetal mice. Am J Physiol Regul Integr Comp Physiol. 2008;295(6):R1973–81. http://dx.doi.org/10.1152/ajpregu.00053.2008

  15. Florio P, Perrone S, Luisi S, Vezzosi P, Longini M, Marzocchi B, et al. Increased plasma concentrations of activin a predict intraventricular hemorrhage in preterm newborns. Clin Chem. 2006;52(8):1516–21. http://dx.doi.org/10.1373/clinchem.2005.065979

  16. Volpe JJ. Neurology of the newborn. 5th ed. Philadelphia: Saunders Elsevier; 2008. p. 517–86.

  17. Ballabh P. Intraventricular hemorrhage in premature infants: mechanism of disease. Pediatr Res. 2010;67(1):1–8. http://dx.doi.org/10.1203/PDR.0b013e3181c1b176

  18. Whitelaw A. Core concepts : intraventricular hemorrhage. NeoReviews. 2011;12(2):94–101. http://dx.doi.org/10.1542/neo.12-2-e94

  19. Bassan H. Intracranial hemorrhage in the preterm infant: understanding it, preventing it. Clin Perinatol. 2009;36(4):737–62. http://dx.doi.org/10.1016/j.clp.2009.07.014

  20. Morakami P. Pittfalls in interpreting umbilical cord blood gases and lactate at birth [disertation]. Norway. Oslo University; 2013.p.15–30.

  21. Wills ED. Evaluation of lipid peroxidation in lipids and biological membranes. In: Snell K, Mullock B, editors. Biochemical toxicology: a practical approach. Irlandia Oxford University Press; 1987. p.127–52.

  22. Ellman GL. Tissue sulfhydryl groups. Arch Biochem Biophys. 1959;82(1):70–7. http://dx.doi.org/10.1016/0003-9861(59)90090-6

  23. Jusuf HA. Panduan praktis histoteknik dasar dan pulasan jaringan rutin. Bagian Histologi Universitas Indonesia. 2011. p.1–34. Indonesian.

  24. Moenadjat Y. Disfungsi endotel dan penguraian endothelial junction pada luka bakar kritis dan luka bakar non kritis [disertasi]. Jakarta: Universitas Indonesia; 2012. p. 68–83. Indonesian.

  25. Jung SN, Yang WK, Kim J, Kim HS, Kim EJ, Yun H, et al. Reactive oxygen species stabilize hypoxia-inducible factor-1 alpha protein and stimulate transcriptional activity via AMP-activated protein kinase in DU145 human prostate cancer cells. Carcinogenesis. 2008;29(4):713–21. http://dx.doi.org/10.1093/carcin/bgn032

  26. Wanandi SI, Dewi S, Paramita R. Ekspresi relatif mRNA HIF-1α pada jantung, otak dan darah tikus selama hipoksia sitemik. Makara Sains. 2009;13(2):185–8. Indonesian.

  27. Jusman SW. Respon jaringan hati terhadap hipoksia sistemik kronik: regulasi ekspresi gen sitoglobin oleh hypoxia-inducible factor-1α [disertation]. Jakarta. Universitas Indonesia; 2010. p. 38–107. Indonesian.

  28. Conde E, Alegre L, Blanco-Sánchez I, Sáenz-Morales D, Aguado-Fraile E, Ponte B, et al. Hypoxia inducible factor 1-alpha (HIF-1 alpha) is induced during reperfusion after renal ischemia and is critical for proximal tubule cell survival. PloS One. 2012;7(3):e33258. http://dx.doi.org/10.1371/journal.pone.0033258

  29. Davis JM, Auten RL. Maturation of the antioxidant system and the effects on preterm birth. Semin Fetal Neonatal Med. 2010;15(4):191–5. http://dx.doi.org/10.1016/j.siny.2010.04.001

  30. Lee JW, Davis JM. Future applications of antioxidants in premature infants. Curr Opin Pediatr. 2011;23(2):161–6. http://dx.doi.org/10.1097/MOP.0b013e3283423e51

  31. Lum H, Roebuck KA. Oxidant stress and endothelial cell dysfunction. Am J Physiol Cell Physiol. 2001;280(4):C719–41.

  32. Dalle-Donne I, Rossi R, Giustarini D, Milzani A, Colombo R. Protein carbonyl groups as biomarkers of oxidative stress. Clin Chim Acta. 2003;329(1–2):23–38. http://dx.doi.org/10.1016/S0009-8981(03)00003-2

  33. Kevil CG, Ohno N, Gute DC, Okayama N, Robinson SA, Chaney E, Alexander JS. Role of cadherin internalization in hidrogen peroxidase-mediated endothelial permeability. Free Radic Biol Med. 1998;24(6):1015–22. http://dx.doi.org/10.1016/S0891-5849(97)00433-4

  34. Hirata J, Ko JA, Mochizuki H, Funaishi K, Yamane K, Sonoda KH, et al. Oxidative stress regulates expression of claudin-1 in human RPE cells. Cent Eur J Biol. 2014;9(5):461–8. http://dx.doi.org/10.2478/s11535-014-0287-0

  35. Haorah J, Knipe B, Leibhart J, Ghorpade A, Persidsky Y. Alcohol-induced oxidative stress in brain endothelial cells causes blood-brain barrier dysfunction. J Leukoc Biol. 2005;78(6):1223–32. http://dx.doi.org/10.1189/jlb.0605340

  36. Wang YL, Hui JN, Guo B, Ma JX. Strengthening tight junctions of retinal microvascular endothelial cells by pericytes under normoxia involving angiopoietin-1 signal way. Eye (Lond). 2007;21(12):1501–10. http://dx.doi.org/10.1038/sj.eye.6702716

Published
2016-10-14
How to Cite
1.
Ekawati M, Mujihartini N, Jusuf AA, Dharmasetiawani N, Jusman SW, Sadikin M. Altered expressions of endothelial junction protein of placental capillaries in premature infants with intraventricular hemorrhage. Med J Indones [Internet]. 2016Oct.14 [cited 2019Dec.15];25(3):143-50. Available from: http://mji.ui.ac.id/journal/index.php/mji/article/view/1287
Section
Clinical Research

Most read articles by the same author(s)