Year 2011, Volume 28 , Issue 4, Pages 162 - 167 2012-01-27

Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması

Ali OKUYUCU [1] , Abdulkerim BEDİR [2] , Zeliha ÖZMEN [3]


ÖZET Roziglitazon; Tip II diabet tedavisinde kullanılan tiazolidinedion grubu bir ilaçtır. Bu grup ilaçlar, karbonhidrat ve lipid metabolizmasını kontrol eden genlerin ekspresyonu¬nun düzenlenmesinde görev alan peroksizom proliferatör aktive reseptör-gama (PPAR-gama)’nın ligandı olarak rol oynarlar. Telomer; kromozom uçlarında bulunan özelleşmiş DNA ve protein kompleksinden oluşmaktadır. Omurgalılarda telomerik DNA, TTAGGG gibi, guaninden zengin dizelerden oluşur. Normal hücrelerde, her DNA replikasyon per¬yodunda, telomer 50–150 baz kısalır. Tamir edilemeyen oksidatif DNA hasarı da bu te¬lomer kısalmasına katkıda bulunabilir. Literatürde, roziglitazonun telomer uzunluğuna etkisini gösteren bir çalışma bulunmamaktadır. Bu nedenle, çalışmamızda roziglitazonun telomer uzunluğuna etkisini araştırmayı amaçladık. Çalışmada 7–8 haftalık, 248-275 g arasında, 16 tane erkek Sprague-Dawley cinsi rat kullanıldı. Ratlar; her grupta dört tane olacak şekilde dört gruba ayrıldı ve 14 gün boyunca 0, 0,5, 1,0 ve 2,0 mg/kg dozlarında roziglitazon oral yoldan uygulandı. Rat karaciğer, ince bağırsak, pankreas dokuları ve lenfositlerinden genomik DNA izolasyonu yapıldı. Numunelerde genom sayısını belir¬leyebilmek için tek kopya gen olarak 36B4 geni seçildi. 36B4 genine spesifik primerle¬rin kullanıldığı Q-PCR ile bir rat dokusundaki genom kopya sayısı bulundu. Rat genom standardı olarak kullanılan bu numune tüm numunelerdeki genom sayısını bulmak için kullanıldı. Tüm numunelerde telomer (T) ve 36B4 (S) için kantitatif PCR yapıldı. İki ça¬lışmada ile elde edilen ürünler birbirine oranlarak her numune için T/S oranı daha sonra da bir kalibratör numune kullanılarak relatif T/S oranı hesaplandı. Ayrıca 10,2 kb telo¬mer standardı kullanarak numunelerin telomer uzunlukları kilobaz olarak da hesaplandı. Farklı roziglitazon dozları verilen numuneleri kontrol grubları ile karşılaştırıldığımızda telomer uzunluğu açısından istatistiksel olarak anlamlı bir fark bulamadık (p>0,05). Bu sonuç, roziglitazonun farklı rat dokularında telomer kısalmasına yol açmadığını göstermektedir. Research on the effect of rosiglitazon on telomere dynamics with molecular methods in rats ABSTRACT Rosiglitazone that is a drug for the treatment of type II diabetes mellitus, belong to the class of thiazolidinediones. Drugs of this class act as ligands for the peroxisome prolif¬erator-activated receptor-gamma (PPAR-gamma), which is involved in the regulation of genes controlling carbohydrate and lipid metabolism. Telomeres are composed of spe¬cialized DNA and protein complexes. Telomeric DNA consist of guanine-rich sequences, such as TTAGGG in vertebrates. In normal cells, telomeres shorten by ~50–150 bp with each round of DNA replication. In addition to this, unrepaired oxidative DNA damage can also contribute to telomere shortening. There is no study that shows the effect of rosiglitazone on telomere length in literature. Because of this, we aimed to research on the effect of rosiglitazone on the telomere length in our study. We used sixteen male Sprague- Dawley rats that at 7-8 weeks of age and weighing 248–275 g in our study. The rats were divided into four groups, four rats in each group, and dosed once a day for 14 days by oral gavage with doses of 0.0, 0.5, 1.0, and 2.0 mg/kg rosiglitazone. Genomic DNA was extracted from rat liver, small intestine, pancreas tissue and lymphocytes. The 36B4 genewas chosen as single copy gene for determine the number of genom in the samples. The number of genome copies were found in a rat tissue by qPCR that is used the 36B4 gene-specific primers. This sample, that is used as rat genom standarts, was used for find the number of genome in all samples. The qPCR was performed for telomere (T) and 36B4 (S) in all samples. The T / S ratio was calculated by the ratio of the products derived from two studies to each other, and then the relative T / S ratio was calculated by using a calibrator sample for each sample. In addition, telomere lengths of the samples were also calculated as kilobase by using 10,2 kb long telomere standard. We did not found statistically any significant difference between doses of rosiglitazone and control groups for telomere length (p>0.05). This result has showed that rosiglitazone doesn’t lead to telomere shortening. J. Exp. Clin. Med., 2011; 28:162-167
PPAR-gama, Thiazolidinedion, Roziglitazon, Telomer, Oksidatif stres, Kantitatif PCR
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Primary Language en
Journal Section Basic Medical Sciences
Authors

Author: Ali OKUYUCU

Author: Abdulkerim BEDİR

Author: Zeliha ÖZMEN

Dates

Acceptance Date : May 26, 2020
Publication Date : January 27, 2012

Bibtex @ { omujecm217024, journal = {Journal of Experimental and Clinical Medicine}, issn = {1309-4483}, eissn = {1309-5129}, address = {}, publisher = {Ondokuz Mayıs University}, year = {2012}, volume = {28}, pages = {162 - 167}, doi = {10.5835/jecm.omu.28.04.008}, title = {Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması}, key = {cite}, author = {OKUYUCU, Ali and BEDİR, Abdulkerim and ÖZMEN, Zeliha} }
APA OKUYUCU, A , BEDİR, A , ÖZMEN, Z . (2012). Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması. Journal of Experimental and Clinical Medicine , 28 (4) , 162-167 . Retrieved from https://dergipark.org.tr/en/pub/omujecm/issue/20423/217024
MLA OKUYUCU, A , BEDİR, A , ÖZMEN, Z . "Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması". Journal of Experimental and Clinical Medicine 28 (2012 ): 162-167 <https://dergipark.org.tr/en/pub/omujecm/issue/20423/217024>
Chicago OKUYUCU, A , BEDİR, A , ÖZMEN, Z . "Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması". Journal of Experimental and Clinical Medicine 28 (2012 ): 162-167
RIS TY - JOUR T1 - Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması AU - Ali OKUYUCU , Abdulkerim BEDİR , Zeliha ÖZMEN Y1 - 2012 PY - 2012 N1 - DO - T2 - Journal of Experimental and Clinical Medicine JF - Journal JO - JOR SP - 162 EP - 167 VL - 28 IS - 4 SN - 1309-4483-1309-5129 M3 - UR - Y2 - 2020 ER -
EndNote %0 Journal of Experimental and Clinical Medicine Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması %A Ali OKUYUCU , Abdulkerim BEDİR , Zeliha ÖZMEN %T Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması %D 2012 %J Journal of Experimental and Clinical Medicine %P 1309-4483-1309-5129 %V 28 %N 4 %R %U
ISNAD OKUYUCU, Ali , BEDİR, Abdulkerim , ÖZMEN, Zeliha . "Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması". Journal of Experimental and Clinical Medicine 28 / 4 (January 2012): 162-167 .
AMA OKUYUCU A , BEDİR A , ÖZMEN Z . Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması. J. Exp. Clin. Med.. 2012; 28(4): 162-167.
Vancouver OKUYUCU A , BEDİR A , ÖZMEN Z . Ratlarda roziglitazon’un telomer dinamiğine etkisinin moleküler yöntemlerle araştırılması. Journal of Experimental and Clinical Medicine. 2012; 28(4): 167-162.