Association of Neonatal Asphyxia With Serum Levels of Heat Shock Protein 27 in a Small Sample of Newborns

  • Ahmadshah Farhat Neonatal Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Mojtaba Shafiee Department of Nutrition, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Ashraf Mohammadzadeh Neonatal Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Reza Saeidi Neonatal Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Rana Amiri Neonatal Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
  • Majid Ghayour Mobarhan Metabolic Syndrome Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
Keywords: Neonatal asphyxia, Apgar score, Heat shock protein-27


Neonatal asphyxia is a state of hypoxia and hypercapnia caused by failure to breathe spontaneously and regularly soon after birth. Heat shock proteins (HSPs) are a ubiquitous and diverse group of highly conserved proteins which are rapidly up-regulated following periods of cellular stress including exposure to heat, ultraviolet irradiation, or chemical toxicity. The aim of the current study was to explore whether there is a relation between serum levels of HSP27 and neonatal asphyxia in a small sample of newborns. A total of 25 healthy newborns and 25 newborns diagnosed with neonatal asphyxia were recruited form Imam Reza Hospital, Mashhad, Iran. The Apgar score was recorded at one minute after delivery by trained nurses and newborns with the Apgar score of less than 7 were considered to be asphyctic. The mean birth weight of newborns in the case and control groups were 3110.47±613.5 g and 3230.4±584.83 g, respectively (P=0.4). Moreover, the mean maternal age of infants in the case group was higher than the mean maternal age of infants in the control group (31.1±6.1 vs. 30.1±5.0). Although it was marginally significant, the level of HSP27 was higher in the case group than the control group (0.23±0.08 vs. 0.19±0.09; P=0.07). Levels of HSP27 were found to be higher in newborns with neonatal asphyxia compared with healthy controls.



Gomella TL, Cunningham MD, Eyal FG, Zenk KE. Neonatology: management, procedures, on-call problems, diseases, and drugs: McGraw-Hill New York; 2004.

Low JA. Intrapartum fetal asphyxia: definition, diagnosis, and classification. American journal of obstetrics and gynecology. 1997;176(5):957-9.

Wyckoff M, Perlman J. Cardiopulmonary resuscitation in very low birth weight infants. Pediatrics. 2000;106(3):618-20.

Pin TW, Eldridge B, Galea MP. A review of developmental outcomes of term infants with post-asphyxia neonatal encephalopathy. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2009;13(3):224-34.

Gluckman PD, Pinal CS, Gunn AJ. Hypoxic-ischemic brain injury in the newborn: pathophysiology and potential strategies for intervention. Seminars in neonatology : SN. 2001;6(2):109-20.

Shah P, Riphagen S, Beyene J, Perlman M. Multiorgan dysfunction in infants with post-asphyxial hypoxic-ischaemic encephalopathy. Archives of disease in childhood Fetal and neonatal edition. 2004;89(2):F152-5.

Apgar V. A proposal for a new method of evaluation of the newborn infant. Current researches in anesthesia & analgesia. 1953;32(4):260-7.

Leuthner SR, Das UG. Low Apgar scores and the definition of birth asphyxia. Pediatric clinics of North America. 2004;51(3):737-45.

Statistics NCfH. The International Classification of Diseases, 9th Revision, Clinical Modification: Procedures: tabular list and alphabetic index: US Department of Health and Human Services, Public Health Service, Health Care Financing Administration; 1980.

Richter-Landsberg C. Heat Shock Proteins. Heat Shock Proteins in Neural Cells: Springer; 2009. p. 1-12.

Gething MJ, Sambrook J. Protein folding in the cell. Nature. 1992;355(6355):33-45.

Welch WJ. The role of heat-shock proteins as molecular chaperones. Current opinion in cell biology. 1991;3(6):1033-8.

Craig EA. Chaperones: helpers along the pathways to protein folding. Science. 1993;260(5116):1902-3.

Hartl FU, Hayer-Hartl M. Molecular chaperones in the cytosol: from nascent chain to folded protein. Science. 2002;295(5561):1852-8.

Muralidharan S, Mandrekar P. Cellular stress response and innate immune signaling: integrating pathways in host defense and inflammation. Journal of leukocyte biology. 2013;94(6):1167-84.

Willis MS, Patterson C. Hold me tight: Role of the heat shock protein family of chaperones in cardiac disease. Circulation. 2010;122(17):1740-51.

Lanneau D, Wettstein G, Bonniaud P, Garrido C. Heat shock proteins: cell protection through protein triage. TheScientificWorldJournal. 2010;10:1543-52.

Mosser DD, Caron AW, Bourget L, Denis-Larose C, Massie B. Role of the human heat shock protein hsp70 in protection against stress-induced apoptosis. Mol Cell Biol. 1997;17(9):5317-27.

Ghayour-Mobarhan M, Saber H, Ferns GA. The potential role of heat shock protein 27 in cardiovascular disease. Clinica chimica acta; international journal of clinical chemistry. 2012;413(1-2):15-24.

Nakamoto H, Vigh L. The small heat shock proteins and their clients. Cellular and molecular life sciences : CMLS. 2007;64(3):294-306.

Mehlen P, Preville X, Chareyron P, Briolay J, Klemenz R, Arrigo AP. Constitutive expression of human hsp27, Drosophila hsp27, or human alpha B-crystallin confers resistance to TNF- and oxidative stress-induced cytotoxicity in stably transfected murine L929 fibroblasts. Journal of immunology (Baltimore, Md : 1950). 1995;154(1):363-74.

Garrido C, Ottavi P, Fromentin A, Hammann A, Arrigo AP, Chauffert B, et al. HSP27 as a mediator of confluence-dependent resistance to cell death induced by anticancer drugs. Cancer Res. 1997;57(13):2661-7.

Mehlen P, Schulze-Osthoff K, Arrigo AP. Small stress proteins as novel regulators of apoptosis. Heat shock protein 27 blocks Fas/APO-1- and staurosporine-induced cell death. The Journal of biological chemistry. 1996;271(28):16510-4.

Child DF, Hudson PR, Hunter-Lavin C, Mukhergee S, China S, Williams CP, et al. Birth defects and anti-heat shock protein 70 antibodies in early pregnancy. Cell Stress Chaperones. 2006;11(1):101-5.

Jiang KW, Yang CW, Shui QX, Xia ZZ, Zhang Y. [Time-course of mu-calpain activation, c-Fos, c-Jun, HSP70 and HSP27 expression in hypoxic-ischemic neonatal rat brain]. Zhonghua er ke za zhi = Chinese journal of pediatrics. 2004;42(6):441-5.

Boskabadi H, Omidian M, Tavallai S, Mohammadi S, Parizadeh M, Ghayour Mobarhan M, et al. Serum Hsp70 Antigen: Early Diagnosis Marker in Perinatal Asphyxia. Iranian journal of pediatrics. 2015;25(2):e381.

Finster M, Wood M. The Apgar score has survived the test of time. Anesthesiology. 2005;102(4):855-7.

Heidari-Bakavoli AR, Sahebkar A, Mobara N, Moohebati M, Tavallaie S, Rahsepar AA, et al. Changes in plasma level of heat shock protein 27 after acute coronary syndrome. Angiology. 2012;63(1):12-6.

Thorat VN, Suryakar AN, Sardeshmukh AS, Sarawade SS. Oxidants and antioxidants in hypoxic ischaemic encephalopathy. Indian journal of clinical biochemistry : IJCB. 2004;19(2):32-5.

Žitňanová I, Šimko M, Sumegová K, Korytár P, Maruniaková A, Demelová D, et al. Markers of oxidative stress in umbilical cord blood in hypoxic newborns. J Pediatr Neonatol. 2004;1.

Bhatia BD, Goel A. Study of free radicals in neonates born through meconium stained amniotic fluid deliveries. Indian pediatrics. 2005;42(9):956-7.

Mondal N, Bhat BV, Banupriya C, Koner BC. Oxidative stress in perinatal asphyxia in relation to outcome. Indian journal of pediatrics. 2010;77(5):515-7.

Kumar A, Ramakrishna SVK, Basu S, Rao GRK. Oxidative stress in perinatal asphyxia. Pediatric neurology. 2008;38(3):181-5.

Fellman V, Raivio KO. Reperfusion injury as the mechanism of brain damage after perinatal asphyxia. Pediatr Res. 1997;41(5):599-606.

Preville X, Salvemini F, Giraud S, Chaufour S, Paul C, Stepien G, et al. Mammalian small stress proteins protect against oxidative stress through their ability to increase glucose-6-phosphate dehydrogenase activity and by maintaining optimal cellular detoxifying machinery. Exp Cell Res. 1999;247(1):61-78.

Arrigo AP, Virot S, Chaufour S, Firdaus W, Kretz-Remy C, Diaz-Latoud C. Hsp27 consolidates intracellular redox homeostasis by upholding glutathione in its reduced form and by decreasing iron intracellular levels. Antioxid Redox Signal. 2005;7(3-4):414-22.

Mehlen P, Kretz-Remy C, Preville X, Arrigo AP. Human hsp27, Drosophila hsp27 and human alphaB-crystallin expression-mediated increase in glutathione is essential for the protective activity of these proteins against TNFalpha-induced cell death. Embo j. 1996;15(11):2695-706.

Kelly S, Zhang ZJ, Zhao H, Xu L, Giffard RG, Sapolsky RM, et al. Gene transfer of HSP72 protects cornu ammonis 1 region of the hippocampus neurons from global ischemia: influence of Bcl-2. Annals of neurology. 2002;52(2):160-7.

David JC, Boelens WC, Grongnet JF. Up-regulation of heat shock protein HSP 20 in the hippocampus as an early response to hypoxia of the newborn. Journal of neurochemistry. 2006;99(2):570-81.

Nakasono I. [Application of immunohistochemistry for forensic pathological diagnosis: finding of human brain in forensic autopsy]. Nihon hoigaku zasshi = The Japanese journal of legal medicine. 2001;55(3):299-309.

How to Cite
Farhat A, Shafiee M, Mohammadzadeh A, Saeidi R, Amiri R, Ghayour Mobarhan M. Association of Neonatal Asphyxia With Serum Levels of Heat Shock Protein 27 in a Small Sample of Newborns. Acta Med Iran. 57(5):303-307.