• The genes expression which is encoding enzyme key reactions of folate-dependent metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy
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The genes expression which is encoding enzyme key reactions of folate-dependent metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy

PERINATOLOGIYA I PEDIATRIYA.2014.4(60):24–30;doi10.15574/PP.2014.60.24

 

The genes expression which is encoding enzyme key reactions of folate-dependent metabolism in human placenta in the first and third trimesters of uncomplicated pregnancy

K.L. Korneyeva1, R.R. Rodriges1, S.V. Ralchenko2, A.V. Vakulenko2, L.V. Manzhula3, V.T. Melnik4, O.Yu. Vereshchak4, M.Yu. Obolenskaya1

 

1Institute of Molecular Biology and Genetics, National Academy of Sciences of Ukraine, Kiev, Ukraine

2Taras Shevchenko Natsionalny University, Kiev, Ukraine

3Maternity Hospital № 3, Kyiv, Ukraine

4Irpin Maternity Hospital, Irpin, Ukraine

 

 

Introduction. Folate-dependent metabolism of one-carbon fragments – is a metabolic system of interconnected reactions responsible for basic biological processes in the cell: development and division, regulation of gene expression by means of methylation. According to the recent studies was found the course of pregnancy and the health of the mother and fetus due to the operation of this system.

 

Purpose — to determine the gene expression of this system responsible for the synthesis of nucleic acid precursors, and accordingly for the proliferation, the expression of genes responsible for the synthesis of the intracellular energy carriers, as well as for the synthesis of methionine and the dependent methylation processes; provide a quantitative characterization of the expression of presented genes at the level of RNA in the placentas of the first and the third trimesters of pregnancy.

 

Method. Polymerase chain reaction method was used in the work.

 

Results. In comparison with the early stages of pregnancy, in the mature placenta was found three_time reduction of RNA containing, encoding the last stage of the purines and methionine synthesis. The reactions of the previous folate-dependent stages of the purine synthesis and cytidine monophashate methylation during the process of thymidylate synthesis hardly changed at the end of pregnancy in comparison with the first trimester.

 

Conclusions. These results can be as a baseline quantitative data for evaluation of changes in the system of folate-dependent metabolism of one-carbon fragments in pathological conditions and during the all period of pregnancy.

 

Key words: folate-dependent metabolism of one-carbon fragments, gene expression, uncomplicated pregnancy.

 

 

REFERENCES

 

 

1. Марценюк ОП, Романець КЛ, Оболенська МЮ, Хупертц Б. 2009. Вплив гомоцистеїну на структуру та функції трофобласта плаценти людини. Український біохімічний журнал. 81,5: 40—49.

2. Оболенська МЮ, Родрігес РР, Марценюк ОП. 2011. Фолатзалежні процеси у плаценті людини: експресія генів, амінотіоли, проліферація і апоптоз. Український біохімічний журнал. 83,1: 5—17.

3. Родрігес РР, Лущик ІС, Оболенська МЮ. 2012. Стехіометрична модель фолатзалежного метаболізму одновуглецевих груп у плаценті людини. Український біохімічний журнал. 84,4: 20—31.

4. Daubner SC, Schrimsher JL, Schendel FJ et al. 1985. A multifunctional protein possessing glycinamide ribonucleotide synthetase, glycinamide ribonucleotide transformylase, and aminoimidazole ribonucleotide synthetase activities in de novo purine biosynthesis. Biochemistry. 24,25: 7059—7062.

5. Muratore CR, Hodgson NW, Trivedi MS et al. 2013. Age-dependent decrease and alternative splicing of methionine synthase mRNA in human cerebral cortex and an accelerated decrease in autism. PloS one. 8,2: 1—15. http://dx.doi.org/10.1371/journal.pone.0056927; PMid:23437274 PMCid:PMC3577685

6. Alexiou M, Leese HJ. 1992. Purine utilisation, de novo synthesis and degradation in mouse preimplantation embryos. Development. 114: 185—192.

7. Blom HJ, Smulders Y. 2011. Overview of homocysteine and folate metabolism. With special references to cardiovascular disease and neural tube defects. J Inherit Metab Dis. 34: 75—81. http://dx.doi.org/10.1007/s10545-010-9177-4; PMid:20814827 PMCid:PMC3026708

8. Bulock KG, Beardsley GP, Anderson KS. 2002. The kinetic mechanism of the human bifunctional enzyme ATIC (5-amino-4-imidazolecarboxamide ribonucleotide transformylase/inosine 5-monophosphate cyclohydrolase). A surprising lack of substrate channeling. J of Biol Chemistry. 277,25: 22168—22174.

9. Caperelli CA, Giroux EL. 1997. The human glycinamide ribonucleotide transformylase domain: purification, characterization, and kinetic mechanism. Archives of biochemistry and biophysics. 341,1: 98—103.

10. Sugita T, Aya H, Ueno M et al. 1997. Characterization of molecularly cloned human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase. J Biochem. 122,2: 309—313.

11. Constancia M, Kelsey G, Reik W. 2004. Resourceful imprinting. Nature. 432,7013: 53—57.

12. Aimi J, Qiu H, Illiams J et al. 1990. De novo purine nucleotide biosynthesis: cloning of human and avian cDNAs encoding the trifunctional glycinamide ribonucleotide synthetase-aminoimidazole ribonucleotide synthetase-glycinamide ribonucleotide transformylase by functional complementation in E. Coli. Nucl Acids Res. 18(22): 6665—6672.

13. Solanky N, Requena A Jimenez, D'Souza SW et al. 2010. Expression of folate transporters in human placenta and implications for homocysteine metabolism. Placenta. 31: 134—143. http://dx.doi.org/10.1016/j.placenta.2009.11.017; PMid:20036773

14. Finkelstein JD. 2000. Pathways and regulation of homocysteine metabolism in mammals. Semin Thromb Hemost. 26,3: 219—225.

15. Finkelstein JD. 1990. Methionine metabolism in mammals. J Nutr Biochem. 1,5: 228—237.

16. Gueant JL, Namour F, Gueant-Rodriguez RM et al. 2013. Folate and fetal programming: a play in epigenomics? Trends Endocrinol Metab. 24,6: 279—289. http://dx.doi.org/10.1016/j.tem.2013.01.010; PMid:23474063

17. Fox JT, Stover PJ. 2008. Folate-mediated one-carbon metabolism. Vitam Horm. 79: 1—44. http://dx.doi.org/10.1016/S0083-6729(08)00401-9

18. Gabaldon M. 2004. Oxidation of cysteine and homocysteine by bovine albumin. Arch Biochem Biophys. 431,2: 178—188.

19. Schwanhausser B, Busse D, Li N et al. 2011. Global quantification of mammalian gene expression control. Nature. 473,7347: 337—342. http://dx.doi.org/10.1038/nature10098; PMid:21593866

20. Ching YH, Munroe RJ, Moran JL et al. 2010. High resolution mapping and positional cloning of ENU-induced mutations in the Rw region of mouse chromosome 5. BMC Genet. 411: 106. http://dx.doi.org/10.1186/1471-2156-11-106; PMid:21118569 PMCid:PMC3009607

21. Vergis JM, Bulock KG, Fleming KG, Beardsley GP. 2001. Human 5-aminoimidazole-4-carboxamide ribonucleotide transformylase/inosine 5'-monophosphate cyclohydrolase. A bifunctional protein requiring dimerization for transformylase activity but not for cyclohydrolase activity. J of Biol Chemistry. 276,11: 7727—7733.

22. Huppertz B. 2008. Placental origins of preeclampsia: challenging the current hypothesis. Hypertension. 51: 970—975. http://dx.doi.org/10.1161/HYPERTENSIONAHA.107.107607; PMid:18259009

23. Banister CE, Koestler DC, Maccani MA et al. 2011. Infant growth restriction is associated with distinct patterns of DNA methylation in human placentas. Epigenetics. 6: 920—927. http://dx.doi.org/10.4161/epi.6.7.16079; PMid:21758004 PMCid:PMC3154432

24. Koukoura O, Sifakis S, Spandidos DA. 2012. DNA methylation in the human placenta and fetal growth (review). Mol Med Rep. 5,4: 883—889. PMid:22294146 PMCid:PMC3493070

25. Stipanuk MH, Dominy JE, Lee JI, Coloso RM. 2006. Mammalian cysteine metabolism: new insights into regulation of cysteine metabolism. J Nutr. 136 (Suppl 6): 1652S—1659S. PMid:16702335

26. Houseman EA, Christensen BC, Yeh RF et al. 2008. Model-based clustering of DNA methylation array data: a recursive-partitioning algorithm for high-dimensional data arising as a mixture of beta distributions. BMC Bioinformatics. 9: 365—380. http://dx.doi.org/10.1186/1471-2105-9-365; PMid:18782434 PMCid:PMC2553421

27. Scotti M, Stella L, Shearer EJ, Stover PJ. 2013. Modeling cellular compartmentation in one-carbon metabolism. Wiley Interdiscip Rev Syst Biol Med. 5,3: 343—365. http://dx.doi.org/10.1002/wsbm.1209; PMid:23408533

28. Kan JL, Jannatipour M, Taylor SM, Moran RG. 1993. Mouse cDNAs encoding a trifunctional protein of de novo purine synthesis and a related single-domain glycinamide ribonucleotide synthetase. Gene. 137,2: 195—202.

29. Mudd SH., Levy HL. 1989. Disorders of transsulfuration. The Metabolic Basis of Inherited Diseases. 4: 693—734.

30. Henikoff S, Keene MA, Sloan JS et al. 1986. Multiple purine pathway enzyme activities are encoded at a single genetic locus in Drosophila. Proc Natl Acad Sci. 83: 720—724.

31. Mislanova C, Martsenyuk O, Huppertz B, Obolenskaya M. 2011. Placental markers of folate-related metabolism in preeclampsia. Reproduction. 142,3: 467—476. http://dx.doi.org/10.1530/REP-10-0484; PMid:21690209

32. Mikheev AM, Nabekura T, Kaddoumi A et al. 2008. Profiling gene expression in human placentae of different gestational ages: an OPRU Network and UW SCOR Study. Reprod Sci. 15,9: 866—877. http://dx.doi.org/10.1177/1933719108322425; PMid:19050320 PMCid:PMC2702165

33. Arnholdt H, Meisel F, Fandrey K, Lohrs U. 1991. Proliferation of villous trophoblast of the human placenta in normal and abnormal pregnancies. Virchows Arch B Cell Pathol Incl Mol Pathol. 60(6): 365—372.

34. Shlomi T, Fan J, Tang B et al. 2014. Quantitation of cellular metabolic fluxes of methionine. Anal Chem. 86,3: 1583—1591. http://dx.doi.org/10.1021/ac4032093; PMid:24397525 PMCid:PMC4060246

35. Roberts JM, Hubel CA. 2009. The two stage model of preeclampsia: variations on the theme. Placenta 30 (Suppl A): 32—37. http://dx.doi.org/10.1016/j.placenta.2008.11.009; PMid:19070896 PMCid:PMC2680383

36. Chiang PK, Gordon RK, Ta LJ et al. 1996. S-Adenosylmethionine and methylation. FASEBJ. 10,4: 471—480.

37. Stipanuk MH, Ueki I. 2011. Dealing with methionine/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur. J of Inherited Metabolic Disease. 34: 17—32. http://dx.doi.org/10.1007/s10545-009-9006-9; PMid:20162368 PMCid:PMC2901774

38. Stover PJ. 2009. One-carbon metabolism-genome interactions in folate-associated pathologies. J Nutr. 139,12: 2402—2405. http://dx.doi.org/10.3945/jn.109.113670; PMid:19812215 PMCid:PMC2777484

39. Stover PJ, Field MS. 2011. Trafficking of intracellular folates. Adv Nutr. 2,4: 325—331. http://dx.doi.org/10.3945/an.111.000596; PMid:22332074 PMCid:PMC3125682

40. Tarver H, Schmidt CLA. The conversion of methionine to cysteine: experiments with radioactive sulfur. 1939. J of Biol Chemistry. 130: 67—80.

41. Brodsky G, Barnes T, Bleskan J et al. 1997. The human GARS-AIRS-GART gene encodes two proteins which are differentially expressed during human brain development and temporally overexpressed in cerebellum of individuals with Down syndrome. Hum Mol Genet. 6,12: 2043—2050.

42. Tibbetts AS, Appling DR. 2010. Compartmentalization of mammalian folate-mediated one-carbon metabolism. Annu Rev Nutr. 30: 57—81. http://dx.doi.org/10.1146/annurev.nutr.012809.104810; PMid:20645850