Polistemia Vera Olgularında Thiol-Disülfid Homeostasis

Giriş: Bu çalışmanın amacı, Polistemia Vera (PV) olgularında; hücre siklusunun çeşitli basamaklarında, apoptozis ve hücre proliferasyonunda önemli rol oynadığı bilinen tiyol-disülfid homeostasisini incelemeyi amaçladık. Yöntemler: Kırkiki PV olgusu 43 sağlıklı kontrol grubuyla karşılaştırıldı. Serum total (–SH + –S–S–) ve nativ (-SH) tiyol seviyeleri her iki grupta ölçüldü. Dinamik disülfid bağlarının yüzdesi ve (–S–S–) and (–S–S–) × 100/(–SH), (–S–S–) × 100/(–SH + –S–S–), ve –SH ×100/(–SH + –S–S–) oranları Erel ve arkadaşlarının yeni metodu ile hesaplandı. PV olguları ve sağlıklı kontrol grubunun verileri kıyaslandı. Sonuçlar: Her iki grubun yaş ve cinsiyet dağılımları benzerdi. PV grubunda nativ tiyol, total tiyol ve nativ/total tiyol seviyeleri istatiksel olarak anlamlı artmıştı. Tartışma: PV hastalığının doğasıyla uyumlu olarak, PV olgularında dengenin proliferasyon yönüne kaydığı gözlemlendi. Total tiyol (–SH + –S–S), nativ tiyol (–SH)ve nativ /total tiyol oranındaki artışı PV hastalığındaki kontrolsüz proliferasyonla açıklayabiliriz. PV olgularında tiyol/disülfid dengesinin indirgeyici tiyol tarafında olduğunu gösterdik. Tüm bu değişiklikler PV hastalığının patofizyolojisinde olan kontrolsüz proliferasyonla ilişkili olabilir.

Thiol – Disulphide Homeostasis in Polycythemia Vera

Background: Thiol-disulphide homeostasis has vital role in cell signalling mechanisms, regulation of transcription factors andenzymatic activities, signal transduction and regulation of proliferation rate, apoptosis and detoxification and antioxidantprotective mechanism.Objective: This study aims to demonstrate in Polycythemia Vera (PV) patients the thioldisulphide homeostasis which is known toplay a role in cell proliferation, apoptosis and various steps of cell cycle.Design: Descriptive prospective cross-sectional study.Settings: Yildirim Beyazıt University Hospital Ankara, Turkey between 2016-2018.Method: Forty-two PV patients and 43 healthy controls were included in the study. Serum total (–SH + –S–S–) and native (–SH)thiol levels were measured in all subjects. The amount of dynamic disulphide bonds and, the ratio of (–S–S–) and (–S–S–) × 100/(–SH), (–S–S–) × 100/(–SH + –S–S–), and –SH ×100/(–SH + –S–S–) were calculated with automatic method. The data obtained fromthe patient group were compared with the control group.Main outcome measures: The amount of dynamic disulphide bonds and, the ratio of (–S–S–) and (–S–S–) × 100/(–SH), (–S–S–) ×100/(–SH + –S–S–), and –SH ×100/(–SH + –S–S–) were calculated with automatic method in PV patieint and healthy control group.Results: Both groups were similar in terms of age and gender distribution. Compared with the control group, PV group hadsignificantly higher native thiol, total thiol and nativ/total thiol levels.Limitation: The generalizability of the study's findings were limited by the small sample size.Conclusions: In accordance with the nature of the disease, thiol balance in PV patients was in favor of proliferation. Increased totalthiol (–SH + –S–S), native thiol (–SH) levels and native thiol/total thiol ratio might be associated with uncontrolled proliferation.The balance of the thiol-disulphide homeostasis shifted to reductive thiol side in the PV. This change can provocate proliferationstatus of the disease and/or may be secondary to the disease.Conflict of Interest: No conflict of interest was declared by the authors.

___

  • 1.Ruben A. Mesa, Murray N. Silverstein, et all. Population-based incidence and survival figures in essential thrombocythemia and agnogenic myeloid metaplasia: an Olmsted County Study, 1976-1995. Am J Hematol. 1999; 61: 10-5.
  • 2. Erel O, Neselioglu S. A novel and automated assay for thiol/disulphide homeostasis. Clin Biochem. 2014; 47: 326-32.
  • 3. Turell L, Radi R, Alvarez B. The thiol pool in human plasma: the central contribution of albumin to redox processes. Free Radic Biol Med. 2013; 65: 244-53.
  • 4. Kundi H, Erel Ö, Balun A, et all. Association of thiol/disulfide ratio with syntax score in patients with NSTEMI. Scand Cardiovasc J. 2015; 49: 95-100.
  • 5. Li W, Busu C, Circu ML, Aw TY. Glutathione in cerebral microvascular endothelial biology and pathobiology: implications for brain homeostasis. Int J Cell Biol. 2012: 434971.
  • 6. Wondrak GT. Redox-directed cancer therapeutics: molecular mechanisms and opportunities. Antioxid Redox Signal. 2009; 11: 3013-69.
  • 7. Kundi H, Ates I, Kiziltunc E, et all. A novel oxidative stress marker in acute myocardial infarction; thiol/disulphide homeostasis. Am J Emerg Med. 2015; 33: 1567-71.
  • 8. Ateş İ, Ozkayar N, Altay M, et all. Is disulphide/thiol ratio related to blood pressure in masked hypertension? Clin Exp Hypertens. 2016; 38: 150-4
  • 9. Ates I, Kaplan M, Yuksel M, et all. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine. 2016; 51: 47-51.
  • 10. Korkmaz V, Kurdoglu Z, Alisik M, et all. Impairment of thiol-disulphide homeostasis in preeclampsia. J Matern Fetal Neonatal Med. 2016; 3: 1-6
  • 11. Bektas H, Vural G, Gumusyayla S et all. Dynamic thioldisulphide homeostasis in acute ischemic stroke patients. Acta Neurol Belg. 2016; 116: 489-94.
  • 12. Prabhu A, Sarcar B, Kahali S, et all. Cysteine catabolism: a novel metabolic pathway contributing to glioblastoma growth. Cancer Res. 2014; 74: 787–96.
  • 13. Kirlin WG, Cai J, Thompson SA, et all. Glutathione redox potential in response to differentiation and enzyme inducers. Free Radic Biol Med. 1999; 27: 1208– 18.
  • 14. Nkabyo YS, Ziegler TR, Gu LH, et all. Glutathione and thioredoxin redox during differentiation in human colon epithelial (Caco-2) cells. Am J Physiol Gastrointest Liver Physiol 2002; 283: 1352–9.
  • 15. Michiels J.J.,Berneman Z.,Schroyens W, et all. Changing Concepts of Diagnostic Criteria of Myeloproliferative Disorders and the Molecular Etiology and Classification of Myeloproliferative Neoplasms: From Dameshek 1950 to Vainchenker 2005 and Beyond, Acta Haematologica. 2015; 133: 36-51.
  • 16. Cao HC, Lin J, Qian J, et all. Detection of the JAK2 mutation in myeloproliferative neoplasms by asymmetric PCR with unlabeled probe and highresolution melt analysis. J Clin Lab Anal. 2011; 25: 300- 4. doi: 10.1002/jcla.20474.
  • 17. Andersen CL, Bjørn ME, McMullin MF, et all l. Circulating YKL-40 in patients with essential thrombocythemia and polycythemia vera treated with the novel histone deacetylase inhibitor vorinostat. Leuk Res. 2014; 38: 816-21.
  • 18. Bjørn ME, Andersen CL, Jensen MK, et all. Circulating YKL-40 in myelofibrosis a potential novel biomarker of disease activity and the inflammatory state. Eur J Haematol. 2014; 93: 224-8.
  • 19. Klampfl T, Gisslinger H, Harutyunyan AS, et all. Somatic mutations of calreticulin in myeloproliferative neoplasms. N Engl J Med. 2013; 369: 2379-90.
  • 20. Bruchova H, Yoon D, Agarwal AM, et all. Erythropoiesis in polycythemia vera is hyperproliferative and has accelerated maturation. Blood Cells Mol Dis. 2009; 43: 81-7.
  • 21. Laubach JP, Fu P, Jiang X, et all. Polycythemia vera erythroid precursors exhibit increased proliferation and apoptosis resistance associated with abnormal RAS and PI3K pathway activation. Exp Hematol. 2009; 37: 1411-22.
  • 22. Blume KG, Paniker NV, Beutler E. Enzymes of glutathione synthesis in patients with myeloproliferative disorders. Clin Chim Acta. 1973; 45: 281-5.
  • 23. Ates I, Kaplan M, Yuksel M, et all. Determination of thiol/disulphide homeostasis in type 1 diabetes mellitus and the factors associated with thiol oxidation. Endocrine. 2016; 1: 47-51.
  • 24. Yıldırım F, Sermetow K, Aycicek A, et all. Increased oxidative stress in preschool children exposed to passive smoking. J Pediatr (Rio J). 2011; 87: 523-8.
  • 25. Ozler S, Oztas E, Erel O, et al. Impact of Gestational Diabetes Mellitus and Maternal Obesity on Cord Blood Dynamic Thiol/Disulfide Homeostasis. Fetal Pediatr Pathol. 2017; 36: 8-15. doi: 10.1080/15513815.2016.1223237.
  • 26. Babaoglu E, Kilic H, Hezer H, et all. Comparison of thiol/disulphide homeostasis parameters in patients with COPD, asthma and ACOS. Eur Rev Med Pharmacol Sci. 2016; 20: 1537-43.
  • 27. Hanikoglu F, Hanikoglu A, Kucuksayan E, et al. Dynamic Thiol/Disulphide Homeostasis Before and After Radical Prostatectomy in Patients with Prostate Cancer. Free Radic Res. 2016; 50: S79-S84
  • 28. Dirican N, Dirican A, Sen O, et al. Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer? Redox Rep. 2016; 21: 197-203.
  • 29. Guney T, Kanat IF, Alkan A, et al. Assessment of serum thiol/disulfide homeostasis in multiple myeloma patients by a new method. Redox Report. 2017;22: 246-51. doi: 10.1080/13510002.2016.1180100.
  • 30. Aldemir M, Karaguzel E, Okulu E, et all. Evaluation of oxidative stress status and antioxidant capacity in patients with renal cell carcinoma. Cent European J Urol. 2015; 68: 415-20.
Dicle Tıp Dergisi-Cover
  • ISSN: 1300-2945
  • Yayın Aralığı: Yılda 4 Sayı
  • Başlangıç: 1963
  • Yayıncı: Cahfer GÜLOĞLU
Sayıdaki Diğer Makaleler

Prognostic importance of primary tumor location in RAS mutant metastatic colorectal cancer

Nadiye AKDENİZ, MUHAMMET ALİ KAPLAN, Mehmet KÜÇÜKÖNER, Zuhat URAKÇI, Yasin SEZGİN, Senar EBİNÇ, Erkan BİLEN, Oğur KARHAN, Şahin LAÇİN, HÜSEYİN BÜYÜKBAYRAM, Abdurrahman IŞIKDOĞAN

Thiol – Disulphide Homeostasis in Polycythemia Vera

Aysun ŞENTÜRK YIKILMAZ, Şule Mine BAKANAY, Sema AKINCI, Senem MARAl, Fuad MUSTAFAYEV, Murat ALIŞIK, Özcan EREL, İmdat DİLEK

Oral mikronize progesteronun ilk trimester tarama belirteçlerine ve yeni doğan sonuçlarına etkisi

Yusuf MADENDAĞ, Mefküre ERASLAN ŞAHİN, Erdem ŞAHİN, İlknur ÇÖL MADENDAĞ, Mehmet AK

Hemoglobinopati Prevelansı- Bir Üçüncü Basamak Merkez Deneyimi

Promil JAIN, Monika GUPTA, Shivani DUA, Nisha MARWAH, Meenu GILL, Rajeev SEN

Helikobakter Pilori Pozitifliği İle Nötrofil Lenfosit Oranı ve Mpv İlişkisi

Murat AKARSU, Okan DİKKER

A Case Report: Acute Myopia and Angle-Closure Glaucoma Attack after Topiramate use

Adar ASLAN, Uğur KEKLİKÇİ, Kadir BİLGEN

Çocuk Kardiyoloji Polikliniğine Göğüs Ağrısı Şikayeti ile Başvuran Hastaların Etyolojik Değerlendirilmesi

Pınar ÇİÇEK, ALPER AKIN, Meki BİLİCİ, Mehmet TÜRE, Hasan BALIK, KAMİL YILMAZ

Acil Servise Başvuran İskemik İnme Hastalarında Gama Glutamil Transferaz, Ortalama Trombosit Hacmi, Nötrofil Lenfosit Oranı ve Eritrosit Dağılım Genişliği Değerlerinin Prognoz ve Mortalite ile İlişkileri

Nazlı GÖRMELİ KURT, Cahfer GÜLOĞLU, Yusuf TAMAM, Mehmet ÜSTÜNDAĞ, Murat ORAK

Diyabetik Makula Ödeminde Bevacizumab Tedavisi: Gerçek Bir Yaşam Çalışması

Yasin Şakir GÖKER, Kemal TEKİN, Hasan KIZILTOPRAK, Cemile ÜÇGÜL ATILGAN, Pınar KÖSEKAHYA

Güneydoğu Anadolu Bölgesine Hızmet Sunan Bir Hastanenin Sağlık Kuruluna Başvuran Hastalarda Körlük Sebeplerinin Değerlendirilmesi

Seyfettin ERDEM