nach oben

Erschienen in:

01.09.2008

Decreased DNA Methyltransferase 3A and 3B mRNA Expression in Peripheral Blood Mononuclear Cells and Increased Plasma SAH Concentration in Adult Patients with Idiopathic Thrombocytopenic Purpura

verfasst von: Jie Tao, Ming Yang, Zhong Chen, Ying Huang, Qinjun Zhao, Jianhui Xu, He Ren, Hui Zhao, Zhenping Chen, Qian Ren, Renchi Yang

Erschienen in: Journal of Clinical Immunology | Ausgabe 5/2008

Einloggen, um Zugang zu erhalten

Abstract

Objective

DNA methylation is known to play an important role in gene transcription and alterations of methylation contribute to the development of certain disorders such as cancer and immunodeficiency. Recent years have found an increasing interest in the role of epigenetic modifications in the etiology of human autoimmune diseases, such as systemic lupus erythromatosus (SLE) and rheumatoid arthritis (RA). DNA methyltransferases (DNMTs) are involved in the epigenetic control of DNA methylation processes. S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), as the substrate and product of essential cellular methyltransferase reactions, have important indicator action of cellular methylation status. The aim of this study is to explore if DNA methylation plays a role in the pathogenesis of idiopathic thrombocytopenic purpura (ITP).

Methods

DNMT1, DNMT3A, and DNMT3B mRNA expression in peripheral blood mononuclear cells (PBMCs) of adult ITP patients were analyzed by real-time quantitative polymerase chain reaction. Plasma SAM and SAH levels were assayed with reversed-phase high performance liquid chromatography (HPLC).

Results

DNMT3A and DNMT3B mRNA expressions were significantly lower in ITP patients than in healthy controls (p < 0.001), while DNMT1 mRNA expression was not significantly different between the two groups (p = 0.774). Plasma SAH concentration was significantly elevated in ITP patients than in healthy controls (p < 0.05), while the plasma SAM and SAM/SAH were not significantly different between the two groups (p = 0.133, p = 0.624 respectively).

Conclusions

Our observations suggest that aberrant DNA methylation status reflected by increased plasma SAH concentration and decreased mRNA expression levels of DNMT3A and 3B are possibly involved in the pathogenesis of ITP although the precise mechanisms need further study.

Yang R, Han ZC. Pathogenesis and management of chronic idiopathic thrombocytopenic purpura: an update. Int J Hematol. 2000;71(1):18–24.PubMed

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med. 2002;346(13):995–1008. doi:10.1056/NEJMra010501.PubMedCrossRef

Chang M, Nakagawa PA, Williams SA, Schwartz MR, Imfeld KL, Buzby JS, et al. Immune thrombocytopenic purpura (ITP) plasma and purified ITP monoclonal autoantibodies inhibit megakaryocytopoiesis in vitro. Blood 2003;102(3):887–95. doi:10.1182/blood-2002-05-1475.PubMedCrossRef

McMillan R, Wang L, Tomer A, Nichol J, Pistillo J. Suppression of in vitro megakaryocyte production by antiplatelet autoantibodies from adult patients with chronic ITP. Blood 2004;103(4):1364–9. doi:10.1182/blood-2003-08-2672.PubMedCrossRef

Olsson B, Andersson PO, Jernas M, Jacobsson S, Carlsson B, Carlsson LM, et al. T-cell-mediated cytotoxicity toward platelets in chronic idiopathic thrombocytopenic purpura. Nat Med. 2003;9(9):1123–4. doi:10.1038/nm921.PubMedCrossRef

Zhou B, Zhao H, Yang RC, Han ZC. Multi-dysfunctional pathophysiology in ITP. Crit Rev Oncol Hematol. 2005;54(2):107–16. doi:10.1016/j.critrevonc.2004.12.004.PubMedCrossRef

Ansel KM, Lee DU, Rao A. An epigenetic view of helper T cell differentiation. Nat Immunol. 2003;4(7):616–23. doi:10.1038/ni0703-616.PubMedCrossRef

Reik W, Walter J. Evolution of imprinting mechanisms: the battle of the sexes begins in the zygote. Nat Genet. 2001;27(3):255–6. doi:10.1038/85804.PubMedCrossRef

Richardson B. DNA methylation and autoimmune disease. Clin Immunol. 2003;109(1):72–9. doi:10.1016/S1521-6616(03)00206-7.PubMedCrossRef

10.

Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002;16(1):6–21. doi:10.1101/gad.947102.PubMedCrossRef

11.

Januchowski R, Prokop J, Jagodzinski PP. Role of epigenetic DNA alterations in the pathogenesis of systemic lupus erythematosus. J Appl Genet. 2004;45(2):237–48.PubMed

12.

Fitzpatrick DR, Wilson CB. Methylation and demethylation in the regulation of genes, cells, and responses in the immune system. Clin Immunol. 2003;109(1):37–45. doi:10.1016/S1521-6616(03)00205-5.PubMedCrossRef

13.

Fatemi M, Hermann A, Gowher H, Jeltsch A. Dnmt3a and Dnmt1 functionally cooperate during de novo methylation of DNA. Eur J Biochem. 2002;269(20):4981–4. doi:10.1046/j.1432-1033.2002.03198.x.PubMedCrossRef

14.

Bourc’his D, Xu GL, Lin CS, Bollman B, Bestor TH. Dnmt3L and the establishment of maternal genomic imprints. Science 2001;294(5551):2536–9. doi:10.1126/science.1065848.PubMedCrossRef

15.

Chedin F, Lieber MR, Hsieh CL. The DNA methyltransferase-like protein DNMT3L stimulates de novo methylation by Dnmt3a. Proc Natl Acad Sci USA. 2002;99(26):16916–21. doi:10.1073/pnas.262443999.PubMedCrossRef

16.

Sekigawa I, Kawasaki M, Ogasawara H, Kaneda K, Kaneko H, Takasaki Y, et al. DNA methylation: its contribution to systemic lupus erythematosus. Clin Exp Med. 2006;6(3):99–106. doi:10.1007/s10238-006-0103-x.PubMedCrossRef

17.

Lu Q, Kaplan M, Ray D, Ray D, Zacharek S, Gutsch D, et al. Demethylation of ITGAL (CD11a) regulatory sequences in systemic lupus erythematosus. Arthritis Rheum. 2002;46(5):1282–91. doi:10.1002/art.10234.PubMedCrossRef

18.

Yung R, Chang S, Hemati N, Johnson K, Richardson B. Mechanisms of drug-induced lupus. IV. Comparison of procainamide and hydralazine with analogs in vitro and in vivo. Arthritis Rheum. 1997;40(8):1436–43. doi:10.1002/art.1780400811.PubMedCrossRef

19.

Cornacchia E, Golbus J, Maybaum J, Strahler J, Hanash S, Richardson B. Hydralazine and procainamide inhibit T cell DNA methylation and induce autoreactivity. J Immunol. 1988;140(7):2197–000.PubMed

20.

Deng C, Lu Q, Zhang Z, Rao T, Attwood J, Yung R, et al. Hydralazine may induce autoimmunity by inhibiting extracellular signal-regulated kinase pathway signaling. Arthritis Rheum. 2003;48(3):746–56. doi:10.1002/art.10833.PubMedCrossRef

21.

Richardson BC, Strahler JR, Pivirotto TS, Quddus J, Bayliss GE, Gross LA, et al. Phenotypic and functional similarities between 5-azacytidine-treated T cells and a T cell subset in patients with active systemic lupus erythematosus. Arthritis Rheum. 1992;35(6):647–62. doi:10.1002/art.1780350608.PubMedCrossRef

22.

Richardson B, Scheinbart L, Strahler J, Gross L, Hanash S, Johnson M. Evidence for impaired T cell DNA methylation in systemic lupus erythematosus and rheumatoid arthritis. Arthritis Rheum. 1990;33(11):1665–73. doi:10.1002/art.1780331109.PubMedCrossRef

23.

Deng C, Kaplan MJ, Yang J, Ray D, Zhang Z, McCune WJ, et al. Decreased Ras-mitogen-activated protein kinase signaling may cause DNA hypomethylation in T lymphocytes from lupus patients. Arthritis Rheum. 2001;44(2):397–407. doi:10.1002/1529-0131(200102)44:2<397::AID-ANR59>3.0.CO;2-N.PubMedCrossRef

24.

Wang T, Zhao H, Ren H, Guo J, Xu M, Yang R, et al. Type 1 and type 2 T-cell profiles in idiopathic thrombocytopenic purpura. Haematologica 2005;90(7):914–23.PubMed

25.

Melnyk S, Pogribna M, Pogribny IP, Yi P, James SJ. Measurement of plasma and intracellular S-adenosylmethionine and S-adenosylhomocysteine utilizing coulometric electrochemical detection: alterations with plasma homocysteine and pyridoxal 5′-phosphate concentrations. Clin Chem. 2000;46(2):265–72.PubMed

26.

Bestor TH. The DNA methyltransferases of mammals. Hum Mol Genet. 2000;9(16):2395–402. doi:10.1093/hmg/9.16.2395.PubMedCrossRef

27.

Nakao M. Epigenetics: interaction of DNA methylation and chromatin. Gene 2001;278(1–2):25–31. doi:10.1016/S0378-1119(01)00721-1.PubMedCrossRef

28.

Januchowski R, Prokop J, Jagodzinski PP. Role of epigenetic DNA alterations in the pathogenesis of systemic lupus erythematosus. J Appl Genet. 2004;45(2):237–48.PubMed

29.

Okada M, Ogasawara H, Kaneko H, Hishikawa T, Sekigawa I, Hashimoto H, et al. Role of DNA methylation in transcription of human endogenous retrovirus in the pathogenesis of systemic lupus erythematosus. J Rheumatol. 2002;29(8):1678–82.PubMed

30.

Sekigawa I, Okada M, Ogasawara H, Kaneko H, Hishikawa T, Hashimoto H. DNA methylation in systemic lupus erythematosus. Lupus 2003;12(2):79–85. doi:10.1191/0961203303lu321oa.PubMedCrossRef

31.

Yung RL, Richardson BC. Role of T cell DNA methylation in lupus syndromes. Lupus 1994;3(6):487–91. doi:10.1177/096120339400300611.PubMedCrossRef

32.

Yung R, Powers D, Johnson K, Amento E, Carr D, Laing T, et al. Mechanisms of drug-induced lupus. II. T cells overexpressing lymphocyte function-associated antigen 1 become autoreactive and cause a lupuslike disease in syngeneic mice. J Clin Invest. 1996;97(12):2866–71. doi:10.1172/JCI118743.PubMedCrossRef

33.

Quddus J, Johnson KJ, Gavalchin J, Amento EP, Chrisp CE, Yung RL, et al. Treating activated CD4+ T cells with either of two distinct DNA methyltransferase inhibitors, 5-azacytidine or procainamide, is sufficient to cause a lupus-like disease in syngeneic mice. J Clin Invest. 1993;92(1):38–53. doi:10.1172/JCI116576.PubMedCrossRef

34.

Zhang Z, Deng C, Lu Q, Richardson B. Age-dependent DNA methylation changes in the ITGAL (CD11a) promoter. Mech Ageing Dev. 2002;123(9):1257–68.PubMed

35.

Yang J, Deng C, Hemati N, Hanash SM, Richardson BC. Effect of mitogenic stimulation and DNA methylation on human T cell DNA methyltransferase expression and activity. J Immunol. 1997;159(3):1303–9.PubMed

36.

Shivapurkar N, Poirier LA. Tissue levels of S-adenosylmethionine and S-adenosylhomocysteine in rats fed methyl-deficient, amino acid-defined diets for one to five weeks. Carcinogenesis 1983;4(8):1051–7. doi:10.1093/carcin/4.8.1051.PubMedCrossRef

37.

Loehrer FM, Angst CP, Haefeli WE, Jordan PP, Ritz R, Fowler B. Low whole-blood S-adenosylmethionine and correlation between 5-methyltetrahydrofolate and homocysteine in coronary artery disease. Arterioscler Thromb Vasc Biol. 1996;16(6):727–33.PubMed

38.

Yi P, Melnyk S, Pogribna M, Pogribny IP, Hine RJ, James SJ. Increase in plasma homocysteine associated with parallel increases in plasma S-adenosylhomocysteine and lymphocyte DNA hypomethylation. J Biol Chem. 2000;275(38):29318–23. doi:10.1074/jbc.M002725200.PubMedCrossRef

39.

Geisel J, Schorr H, Bodis M, Isber S, Hübner U, Knapp JP, et al. The vegetarian lifestyle and DNA methylation. Clin Chem Lab Med. 2005;43(10):1164–9. doi:10.1515/CCLM.2005.202.PubMedCrossRef

40.

Hoffman DR, Cornatzer WE, Duerre JA. Relationship between tissue levels of S-adenosylmethionine, S-adenylhomocysteine, and transmethylation reactions. Can J Biochem. 1979;57(1):56–65.PubMedCrossRef

41.

De Cabo SF, Santos J, Fernández-Piqueras J. Molecular and cytological evidence of S-adenosyl-L-homocysteine as an innocuous undermethylating agent in vivo. Cytogenet Cell Genet. 1995;71(2):187–92. doi:10.1159/000134104.PubMedCrossRef

42.

Chiang PK, Gordon RK, Tal J, Zeng GC, Doctor BP, Pardhasaradhi K, et al. S-Adenosylmethionine and methylation. FASEB J. 1996;10(4):471–80.PubMed

43.

Loehrer FM, Angst CP, Brunner FP, Haefeli WE, Fowler B. Evidence for disturbed S-adenosylmethionine: S-adenosylhomocysteine ratio in patients with end-stage renal failure: a cause for disturbed methylation reactions? Nephrol Dial Transplant. 1998;13(3):656–61. doi:10.1093/ndt/13.3.656.PubMedCrossRef

44.

Jacob RA, Gretz DM, Taylor PC, James SJ, Pogribny IP, Miller BJ, et al. Moderate folate depletion increases plasma homocysteine and decreases lymphocyte DNA methylation in postmenopausal women. J Nutr. 1998;128(7):1204–12.PubMed

45.

Finkelstein JD. Methionine metabolism in mammals. J Nutr Biochem. 1990;1(5):228–37. doi:10.1016/0955-2863(90)90070-2.PubMedCrossRef

46.

Kredich NM, Martin DW. Role of S-adenosylhomocysteine in adenosine-mediated toxicity in cultured mouse T lymphoma cells. Cell 1977;12(4):931–8. doi:10.1016/0092-8674(77)90157-X.PubMedCrossRef

47.

Cantoni GL. The role of S-adenosylhomocysteine in the biological utilization of S-adenosylmethionine. Prog Clin Biol Res. 1985;198:47–65.PubMed

48.

Wainfan E, Poirier LA. Methyl groups in carcinogenesis: effects on DNA methylation and gene expression. Cancer Res. 1992;52(Suppl 7):2071s–7s.PubMed

49.

Chiang PK, Cantoni GL. Perturbation of biochemical transmethylations by 3-deazaadenosine in vivo. Biochem Pharmacol. 1979;28(12):1897–902. doi:10.1016/0006-2952(79)90642-7.PubMedCrossRef

Titel: Decreased DNA Methyltransferase 3A and 3B mRNA Expression in Peripheral Blood Mononuclear Cells and Increased Plasma SAH Concentration in Adult Patients with Idiopathic Thrombocytopenic Purpura
verfasst von: Jie Tao
Ming Yang
Zhong Chen
Ying Huang
Qinjun Zhao
Jianhui Xu
He Ren
Hui Zhao
Zhenping Chen
Qian Ren
Renchi Yang
Publikationsdatum: 01.09.2008
Verlag: Springer US
Erschienen in: Journal of Clinical Immunology / Ausgabe 5/2008
Print ISSN: 0271-9142
Elektronische ISSN: 1573-2592
DOI: https://doi.org/10.1007/s10875-008-9223-2

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Niedriger diastolischer Blutdruck erhöht Risiko für schwere kardiovaskuläre Komplikationen

25.04.2024 Hypotonie Nachrichten

Wenn unter einer medikamentösen Hochdrucktherapie der diastolische Blutdruck in den Keller geht, steigt das Risiko für schwere kardiovaskuläre Ereignisse: Darauf deutet eine Sekundäranalyse der SPRINT-Studie hin.

Bei schweren Reaktionen auf Insektenstiche empfiehlt sich eine spezifische Immuntherapie

25.04.2024 Allergien und Intoleranzreaktionen Nachrichten

Insektenstiche sind bei Erwachsenen die häufigsten Auslöser einer Anaphylaxie. Einen wirksamen Schutz vor schweren anaphylaktischen Reaktionen bietet die allergenspezifische Immuntherapie. Jedoch kommt sie noch viel zu selten zum Einsatz.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Abstract

Objective

Methods

Results

Conclusions

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2008

Association of Graves’ Disease and Prevalence of Circulating IFN-γ-producing CD28− T Cells

IL1 Gene Cluster Polymorphisms and Its Haplotypes may Predict the Risk to Develop Invasive Pulmonary Aspergillosis and Modulate C-reactive Protein Level

Long-Term Immunological Study in Graves’ Disease Treated with Thyroid Arterial Embolization

Expression of Cytokine mRNA in Lymphocytes of Malnourished Children

Lack of Nonfunctional B-cell Receptor Rearrangements in a Patient with Normal B Cell Numbers Despite Partial RAG1 Deficiency and Atypical SCID/Omenn Syndrome