gaziosmanpaşa tıp dergisi

Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi

1309-3320

Tokat Gaziosmanpaşa Üniversitesi

Clinical Sciences

Klinik Tıp Bilimleri

Roziglitazonun Sıçanlarda Mitokondriyal Genom Üzerindeki Etkisinin Moleküler Yöntemlerle Araştırılması

Investigation of Effect of Rosiglitazone on the Mitochondrial Genome in Rats by Molecular Methods

Özmen

Zeliha Cansel

TOKAT GAZİOSMANPAŞA ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, BİYOKİMYA ANABİLİM DALI Alvur

Muhlise

ONDOKUZ MAYIS ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI Bedir

Abdulkerim

ONDOKUZ MAYIS ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI Bilgici

Birşen

ONDOKUZ MAYIS ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ, TIBBİ BİYOKİMYA ANABİLİM DALI Nar

Rukiye

PAMUKKALE ÜNİVERSİTESİ, TIP FAKÜLTESİ, TEMEL TIP BİLİMLERİ BÖLÜMÜ

09 05 2023

15 1 26 44 02 28 2023 09 05 2023

2009

Gaziosmanpaşa Üniversitesi Tıp Fakültesi Dergisi

Amaç: Roziglitazon, Tip II diabetes mellitus tedavisinde kullanılan tiazolidindion sınıfına ait bir ilaçtır. Bu çalışmanın amacı, farklı sıçan dokularında mtDNA4834 delesyon frekansını inceleyerek, roziglitazonun mitokondriyal DNA üzerindeki etkilerini araştırmaktır.Gereç ve Yöntemler: Sprague-Dawley sıçanlarının karaciğer, ince bağırsak, pankreas dokusu ve lenfositlerinden genomik DNA izole edildi. Numunelerin nükleer DNA, mitokondriyal DNA ve mtDNA4834 delesyon kopya sayıları real-time qPCR ile belirlendi. Hücre başına mtDNA kopya sayıları (mtDNA/hücre) ve mtDNA4834 delesyon frekansı (delesyon frekansı (%)) hesaplandı.Bulgular: mtDNA/hücre, roziglitazonun tüm dozlarında ince bağırsak ve pankreas dokusunda kontrol grubuna göre anlamlı derecede düşüktü (p

Objectives: Rosiglitazone is a drug which belongs to tiazolidinedione class used in the treatment of Type II diabetes mellitus. The aim of this study was to investigate the effects of rosiglitazone on the mitochondrial DNA by examining the frequency of the mtDNA4834 deletion in the different rat tissues.Material and Methods: Genomic DNA was extracted from liver, small intestine, pancreas tissue and lymphocytes of male Sprague-Dawley rats. Nuclear DNA, mitochondrial DNA and mtDNA4834 deletion copy numbers of the samples was determined by real-time qPCR. mtDNA copy numbers per cell (mtDNA/cell) and mtDNA4834 deletion frequency (mtDNA4834 deletion frequency (%)) were calculation.Results: The mtDNA/cell in the tissues of small intestine and pancreas were significiantly lower than in all rosiglitazone doses compared to the control group (p

mtDNA4834 deletion mitochondrial DNA oxidative stress rosiglitazone

mtDNA4834 delesyon mitokondriyal DNA oksidatif stres roziglitazon

1. Tack CJ, Smits P. Thiazolidinedione derivatives in type 2 diabetes mellitus. Neth J Med. 2006;64:166-74.

2. Spiegelman BM. PPAR-g adipogenic regulator and thiazolidinedione receptor. Diabetes. 1998; 47:507–14.

3. Da Ros R, Assaloni R, Ceriello A. The preventive anti-oxidant action of thiazolidinediones: a new therapeutic prospect in diabetes and insulin resistance. Diabet Med. 2004;21:1249-52.

4. Calkin AC, Forbes JM, Smith CM, Lassila M, Cooper ME, Jandeleit-Dahm KA et al. Rosiglitazone attenuates atherosclerosis in a model of insulin insufficiency independent of its metabolic effects. Aterioscler Thromb Vasc Biol. 2005;25:1903–9

5. Rong JX, Qiu Y, Hansen MK, Zhu L, Zhang V, Xie M et al. Adipose mitochondrial biogenesis is suppressed in db/db and high-fat diet-fed mice and improved by rosiglitazone. Diabetes. 2007;56:1751-60.

6. Brunmair B, Staniek K, Gras F, Scharf N, Althaym A, Clara R et al. Thiazolidinediones, like metformin, inhibit respiratory complex I: a common mechanism contributing to their antidiabetic actions? Diabetes. 2004;53:1052–9.

7. Scatena R, Bottoni P, Martorana GE, Ferrari F, De Sole P, Rossi C, et al. Mitochondrial respiratory chain dysfunction, a non-receptor-mediated effect of synthetic PPAR-ligands: biochemical and pharmacological implications. Biochem Biophys Res Comm 2004;319:967-73

8. García-Ruiz I, Rodríguez-Juan C, Díaz-Sanjuán T, Martínez MA, Muñoz-Yagüe T, Solís-Herruzol JA. Effects of Rosiglitazone on the Liver Histology and Mitochondrial Function in ob/ob Mice Hepatology. 2007;46:414-23.

9. Richter C. Reactive oxygen and DNA damage in mitochondria. Mutat. Res. 1992;275: 249–55.

10. Lenaz G. The Mitochondrial Production of ReactiveOxygen Species: Mechanisms and Implications in Human Pathology. IUBMB Life. 2001;52: 159–64

11. Sipos I, Tretter L, Adam-Vizi V. Quantitative relationship between inhibition of respiratory complexes and formation of reactive oxygen species in isolated nerve terminals. J. Neurochem. 2003; 84:112-8

12. Narayanan PK, Hart T, Elcock F, Zhang C, Hahn L, McFarland D et al. Troglitazone-induced intracellular oxidative stress in rat hepatoma cells: a ﬂow cytometric assessment. Cytometry A. 2003;52:28–35.

13. Desjardins P, de Muys JM, Morais R. An established avian fibroblast cell line without mitochondrial DNA. Somat Cell Mol Genet. 1986;12:133-9.

14. Sawyer DE, Van Houten B. Repair of DNA damage in mitochondria. Mutat Res. 1999;434:161–76.

15. Cortopassi GA, Shibata DD, Soong NW, Arnheim N. A pattern of accumulation of a somatic deletion of mitochondrial DNA in aging human tissues. Proc Natl Acad Sci USA. 1992;89:7370–4.

16. Filburn CR, Edris W, Tamatani M, Hogue B, Kudryashova I, Hansford RG. Mitochondrial electron transport chain activities and DNA deletions in regions of the rat brain. Mech Ageing Dev. 1996;87:35–46.

17. Gadaleta MN, Rainaldi G, Lezza AM, Milella F, Fracasso F, Cantatore P. Mitochondrial DNA copy number and mitochondrial DNA deletion in adult and senescent rats. Mutat Res. 1992; 275:181–93.

18. Edris W, Burgett B, Stine OC, Filburn CR. Detection and quantitation by competitive PCR of an age-associated increase in a 4.8kb deletion in rat mitochondrial DNA. Mutat Res. 1994; 316:69–78.

19. Nicklas JA, Brooks EM, Hunter TC, Single R, Branda RF. Development of a Quantitative PCR (TaqMan) Assay for Relative Mitochondrial DNA Copy Number and the Common Mitochondrial DNA Deletion in the Rat. Environmental and Molecular Mutagenesis. 2004;44:313–20.

20. Feinstein DL, Spagnolo A, Akar C, Weinberg G, Murphy P, Gavrilyuk V et al. Receptor-Independent Actions of PPAR Thiazolidinedione Agonists: Is Mitochondrial Function the Key? Biochem Pharmacol 2005; 70:177-88.

21. Bedir A, Aliyazicioğlu Y, Kahraman H, Yurdakul Z, Uysal M, Suvaci DE et al. Genotoxicity in rats treated with the antidiabetic agent, rosiglitazone. Environ Mol Mutagen. 2006;47:718-24.

22. Bedir A, Aliyazicioğlu Y, Bilgici B, Yurdakul Z, Uysal M, Suvaci DE et al. Assessment of genotoxicity in rats treated with the antidiabetic agent, pioglitazone. Environ Mol Mutagen. 2008;49:185-91.

23. Inmaculada GR, Rodriguez-Juan C, Diaz-Sanjuan T, Martinez MA, Munoz-Yague T and Solis-Herruzo J.A. Effects of Rosiglitazone on the Liver Histology and Mitochondrial Function in ob/ob Mice. Hepatology. 2007;46:414-23

24. Shiau CW, Yang CC, Kulp SK, Chen KF, Chen CS, Huang JW. Thiazolidenediones mediate apoptosis in prostate cancer cells in part through inhibition of Bcl-xL/Bcl-2 functions independently of PPARγ. Cancer Res. 2005;65:1561–9.

25. Ceolotto G, Gallo A, Papparella I, Franco L, Murphy E, Iori E et al. Rosiglitazone reduces glucose-induced oxidative stress mediated by NAD(P)H oxidase via AMPK-dependent mechanism. Arterioscler Thromb Vasc Biol. 2007;27:2627-33.

26. Giannini S, Serio M, Galli A. Pleiotropic effects of thiazolidinediones: taking a look beyond antidiabetic activity. J Endocrinol Invest. 2004;27:982-91.

27. Girnun GD, Domann FE, Moore SA, Robbins ME. Identification of a functional peroxisome proliferator-activated receptor response element in the rat catalase promoter. Mol Endocrinol. 2002;16:2793-801.

28. Suematsu N, Tsutsui H, Wen J, Kang D, Ikeuchi M, Ide T et al. Oxidative stress mediates tumor necrosis factor-alpha-induced mitochondrial DNA damage and dysfunction in cardiac myocytes. Circulation. 2003;107:1418–23.

29. Shigenaga MK, Hagen TM, Ames BN. Oxidative damage and mitochondrial decay in aging. Proc Natl Acad Sci. 1994;91:10771-8.

30. Mandavilli BS, Santos JH, Van Houten B. Mitochondrial DNA repair and aging. Mutat Res. 2002;509:127-51.

31. Bravo-Nuevo A, Williams NK, Valter K, Stone J. Relationship between mitochondrial DNA damage andphotoreceptor death in developing and adult retina, assessed in normal and degenerative rat strains. Mitochondrion. 2007;7:340–6.

32. David LY, Bruce NA. Quantitation of age-related mitochondrial DNA deletions in rat tissues shows that their pattern of accumulation differs from that of humans. Gene. 1998;209:23–30.

33. Filser N, Margue C, and Richter C. Quantification of Wild-Type Mitochondrial DNA and Its 4.8-kb Deletion in Rat Organs. Biochemical and Biophysical Research Communications. 1997;233:102–7.

34. Garg R, Kumbkarni Y, Aljada A, Mohanty P, Ghanim H, Hamouda W. Troglitazone reduces reactive oxygen species generation by leukocytes and lipid peroxidation and improves flow-mediated vasodilatation in obese subjects. Hypertension. 2000;36:430–5.

35. Shay JW, Pierce DJ, Werbin H. Mitochondrial DNA copy number is proportional to total cell DNA under a variety of growth conditions. J. Biol. Chem. 1990;265:14802-7.

36. Lee HC, Wei YH. Mitochondrial biogenesis and mitochondrial DNA maintenance of mammalian cells under oxidative stress. Int J Biochem Cell Biol. 2005;37:822-34.

37. Bogacka I, Ukropcova B, McNeil M, Gimble JM, Smith SR. Structural and functional consequences of mitochondrial biogenesis in human adipocytes in vitro. J Clin Endocrinol Metab. 2005;90:6650-6.

38. Masuyama M, Iida R, Takatsuka H, Yasuda T, Matsuki T. Quantitative change in mitochondrial DNA content in various mouse tissues during aging. Biochimica et Biophysica Acta. 2005;1723:302–8.

39. Short KR, Bigelow ML, Kahl J. Decline in skeletal muscle mitochondrial function with aging in humans. Proc Natl Acad Sci. 2005;102:5618–23.

40. Menshikova EV, Ritov VB, Fairfull L, Ferrell RE, Kelley DE, Goodpaster BH. Effects of exercise on mitochondrial content function in aging human skeletal muscle. J Gerontol. 2006;61:534–40.

41. Lynn S, Borthwick GM, Charnley RM, Walker M, Turnbull DM. Heteroplasmic ratio of the A3243G mitochondrial DNA mutation in single pancreatic beta cells. Diabetologia. 2003;46:296–9. 93, 183, 212, 294, 315

42. Lenzen S, Drinkgern J, Tiedge M. Low antioxidant enzyme gene expression in pancreatic islets compared with various other mouse tissues. Free Radic. Biol. Med. 1996;20: 463–6.

43. Moghadasian MH, Godin DV. Gender-related regional antioxidant profiles in the gastrointestinal tract of the rat. Mol Cell Biochem. 1996;155:43–9.

44. Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005;1:361–70

45. St. Pierre J, Lin J, Krauss S, Tarr PT, Yang R, Newgard CB et al. Bioenergetic analysis of peroxisome proliferator-activated receptör gamma coactivators 1alpha and 1beta (PGC-1alpha and PGC-1beta) in muscle cells. J Biol Chem. 2003;278:26597–603.