Prenatal Hypoxia Reduces Mitochondrial Protein Levels and Cytochrome C Oxidase Activity in Offspring Guinea Pig Hearts

Overview

Journal Reprod Sci

Publisher Springer

Specialty Reproductive Medicine

Date 2014 Jan 11

PMID 24406790

Citations 16

Authors

Yazan M Al-Hasan

Gerard A Pinkas

Loren P Thompson

Affiliations

Soon will be listed here.

Abstract

Prenatal hypoxia (HPX) reduces mitochondrial cytochrome c oxidase (CCO and COX) activity in fetal guinea pig (GP) hearts. The aim of this study was to quantify the lasting effects of chronic prenatal HPX on cardiac mitochondrial enzyme activity and protein expression in offspring hearts. Pregnant GPs were exposed to either normoxia (NMX) or HPX (10.5%O) during the last 14 days of pregnancy. Both NMX and HPX fetuses, delivered vaginally, were housed under NMX conditions until 90 days of age. Total RNA and mitochondrial fractions were isolated from hearts of anesthetized NMX and HPX offspring and showed decreased levels of CCO but not medium-chain acyl dehydrogenase activity, protein levels of nuclear- and mitochondrial-encoded COX4 and COX1, respectively, and messenger RNA expression of peroxisome proliferator-activated receptor gamma coactivator 1-alpha, COX5b, and 4.1 compared to NMX controls. Prenatal HPX may alter mitochondrial function in the offspring by disrupting protein expression associated with the respiratory chain.

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References

Hanson M, Gluckman P . Developmental origins of health and disease: new insights. Basic Clin Pharmacol Toxicol. 2008; 102(2):90-3. DOI: 10.1111/j.1742-7843.2007.00186.x. View

Feige J, Auwerx J . Transcriptional coregulators in the control of energy homeostasis. Trends Cell Biol. 2007; 17(6):292-301. DOI: 10.1016/j.tcb.2007.04.001. View

Nouette-Gaulain K, Malgat M, Rocher C, Savineau J, Marthan R, Mazat J . Time course of differential mitochondrial energy metabolism adaptation to chronic hypoxia in right and left ventricles. Cardiovasc Res. 2005; 66(1):132-40. DOI: 10.1016/j.cardiores.2004.12.023. View

Andersson U, Scarpulla R . Pgc-1-related coactivator, a novel, serum-inducible coactivator of nuclear respiratory factor 1-dependent transcription in mammalian cells. Mol Cell Biol. 2001; 21(11):3738-49. PMC: 87014. DOI: 10.1128/MCB.21.11.3738-3749.2001. View

Zhang L . Prenatal hypoxia and cardiac programming. J Soc Gynecol Investig. 2005; 12(1):2-13. DOI: 10.1016/j.jsgi.2004.09.004. View

Barnes S, Ozanne S . Pathways linking the early environment to long-term health and lifespan. Prog Biophys Mol Biol. 2010; 106(1):323-36. DOI: 10.1016/j.pbiomolbio.2010.12.005. View

Finck B, Kelly D . PGC-1 coactivators: inducible regulators of energy metabolism in health and disease. J Clin Invest. 2006; 116(3):615-22. PMC: 1386111. DOI: 10.1172/JCI27794. View

Hashimoto K, Pinkas G, Evans L, Liu H, Al-Hasan Y, Thompson L . Protective effect of N-acetylcysteine on liver damage during chronic intrauterine hypoxia in fetal guinea pig. Reprod Sci. 2012; 19(9):1001-9. PMC: 4046312. DOI: 10.1177/1933719112440052. View

Yang W, Iacono L, Tang W, Chin K . Novel function of the regulatory subunit of protein kinase A: regulation of cytochrome c oxidase activity and cytochrome c release. Biochemistry. 1998; 37(40):14175-80. DOI: 10.1021/bi981402a. View

10.

Ongwijitwat S, Wong-Riley M . Is nuclear respiratory factor 2 a master transcriptional coordinator for all ten nuclear-encoded cytochrome c oxidase subunits in neurons?. Gene. 2005; 360(1):65-77. DOI: 10.1016/j.gene.2005.06.015. View

11.

Dong Y, Hou W, Wei J, Weiner C . Chronic hypoxemia absent bacterial infection is one cause of the fetal inflammatory response syndrome (FIRS). Reprod Sci. 2009; 16(7):650-6. DOI: 10.1177/1933719109333662. View

12.

Kane A, Herrera E, Camm E, Giussani D . Vitamin C prevents intrauterine programming of in vivo cardiovascular dysfunction in the rat. Circ J. 2013; 77(10):2604-11. DOI: 10.1253/circj.cj-13-0311. View

13.

Camm E, Martin-Gronert M, Wright N, Hansell J, Ozanne S, Giussani D . Prenatal hypoxia independent of undernutrition promotes molecular markers of insulin resistance in adult offspring. FASEB J. 2010; 25(1):420-7. DOI: 10.1096/fj.10-158188. View

14.

Patterson A, Chen M, Xue Q, Xiao D, Zhang L . Chronic prenatal hypoxia induces epigenetic programming of PKC{epsilon} gene repression in rat hearts. Circ Res. 2010; 107(3):365-73. PMC: 2919213. DOI: 10.1161/CIRCRESAHA.110.221259. View

15.

Levett D, Radford E, Menassa D, Graber E, Morash A, Hoppeler H . Acclimatization of skeletal muscle mitochondria to high-altitude hypoxia during an ascent of Everest. FASEB J. 2011; 26(4):1431-41. DOI: 10.1096/fj.11-197772. View

16.

Scarpulla R . Nuclear control of respiratory chain expression by nuclear respiratory factors and PGC-1-related coactivator. Ann N Y Acad Sci. 2008; 1147:321-34. PMC: 2853241. DOI: 10.1196/annals.1427.006. View

17.

Prabhakar N . Sensing hypoxia: physiology, genetics and epigenetics. J Physiol. 2013; 591(9):2245-57. PMC: 3650692. DOI: 10.1113/jphysiol.2012.247759. View

18.

Virbasius J, Virbasius C, Scarpulla R . Identity of GABP with NRF-2, a multisubunit activator of cytochrome oxidase expression, reveals a cellular role for an ETS domain activator of viral promoters. Genes Dev. 1993; 7(3):380-92. DOI: 10.1101/gad.7.3.380. View

19.

Jones P, Takai D . The role of DNA methylation in mammalian epigenetics. Science. 2001; 293(5532):1068-70. DOI: 10.1126/science.1063852. View

20.

Thorn S, Regnault T, Brown L, Rozance P, Keng J, Roper M . Intrauterine growth restriction increases fetal hepatic gluconeogenic capacity and reduces messenger ribonucleic acid translation initiation and nutrient sensing in fetal liver and skeletal muscle. Endocrinology. 2009; 150(7):3021-30. PMC: 2703533. DOI: 10.1210/en.2008-1789. View