Jnk İnhibisyonunun Diyabetik Testis Dokusundaki Fas/Fasl Sinyal Yolağına Etkileri
Çalışmamızın amacı, diyabetik erkek sıçanlarda c-Jun N-terminal
kinaz (JNK) inhibisyonunun, apoptotik bir yolak olan Fas/FasL
sinyal yolağına olası etkilerini ortaya koymaktır. Otuz adet Sprague
Dawley erkek sıçandan rastgele beş grup oluşturuldu. Birinci grup:
Kontrol grubu (sadece çözücü verilen grup, n=6), 2. grup: Tek doz
60 mg/kg streptozotosin (STZ) i.p., 15 gün (n=6), 3. grup: 60 mg/kg
STZ, 30 gün (n=6), 4. grup: 60 mg/kg STZ + 15 mg/kg SP600125
(JNK inhibitörü) i.p., 15 gün (n=6), 5. grup: 60 mg/kg (STZ) + 15
mg/kg SP600125, 30 gün (n=6). Deney sonunda, deneklerden alınan
testis doku örnekleri rutin takibe alındı ve parafine gömüldü. Fas,
FasL ve kaspaz 8 proteinleri immünohistokimyal olarak
değerlendirildi. Fas ve kaspaz 8 immünpozitif hücre sayısı tüm
deney gruplarında kontrol grubuna göre, FasL immünpozitif hücre
sayısının ise 4. grup hariç, diğer tüm gruplarda kontrol grubuna göre
anlamlı şekilde arttığı saptanmıştır. Ayrıca Fas, FasL ve kaspaz 8
immünpozitif hücre sayılarının 2. gruba kıyasla 4. grupta, 3. gruba
kıyasla da 5. grupta anlamlı şekilde azaldığı gözlenmiştir. Sonuçta;
diyabetik testis dokusunda meydana gelen apoptoziste, Fas/FasL
sinyal yolağının önemli etkilerinin olduğu ve JNK inhibitörü olan
SP600125’in, JNK ile birlikte Fas/FasL sinyal yolağı üzerinden de,
diyabetik testiküler apoptozisi önlemede önemli bir rol
üstlenebileceği kanısındayız.
The Role of Fas/Fasl Signaling Pathway In Diabetic Testicular Tissue by Administered Jnk Inhibition
We investigated the possible role of the c-Jun N-terminal kinase
(JNK) inhibition on Fas/FasL signaling pathway in diabetes-induced
testicular apoptosis. Thirty Sprague-Dawley male rats, weighing
250–350 g, were randomly divided into five groups. First group:
Control (animals received only vehicle, n=6 ), II. group: single dose
60 mg/kg streptozotocin (STZ) i.p., 15 days (n=6), III. group: 60
mg/kg (STZ), 30 days (n=6), IV. group: 60 mg/kg (STZ) + 15mg/kg
SP600125 (JNK inhibitor) i.p., 15 days (n=6), V. group: 60 mg/kg
(STZ) + 15 mg/kg SP600125, 30 days (n=6). At the end of the
experiments, rats were sacrificed, testis tissue samples were
harvested and there were routinely processed for light microscopy.
Fas, FasL and caspase 8 expressions were evaluated
immunohistochemically. Fas and caspase 8 immunpositive cells
count was significantly increased in all experiment groups compared
with control group. FasL immunpositive cells count was
significantly increased, compared with control, in all groups except
for the fifth group. On the other hand; Fas, FasL and caspase 8
immunpositive cells count was significantly decreased in the fourth
group compared with the second group. Fas, FasL and caspase 8
immunpositive cells count was significantly decreased in the fifth
group compared with the third group. We conclude that Fas / FasL
signaling pathway has significant effects on apoptosis in diabetic
testis and SP600125 may play an important role in preventing
diabetic testicular apoptosis via JNK and Fas / FasL.
___
- 1. Donmez YB, Kizilay G, Topcu-Tarladacalisir Y. MAPK immunoreactivity in streptozotocin-induced diabetic rat testis. Acta Cir Bras. 2014; 29(10): 644- 50.
- 2. Oridupa OA, Folasire OF, Owolabi AJ, Aina O. Effect of Traditional Treatment of Diabetes Mellitus with Xanthosoma sagittifolium on the Male Reproductive System of Alloxan-Induced Diabetic Wistar Rats. Drug Res. 2017; 67(6): 337-42.
- 3. Koh PO. Streptozotocin-induced diabetes increases apoptosis through JNK phosphorylation and Bax activation in rat testes. J Vet Med Sci. 2007; 69(9): 969-71.
- 4. Koh PO. Streptozotocin-induced diabetes increases the interaction of Bad/Bcl-XL and decreases the binding of pBad/14-3-3 in rat testis. Life Sci. 2007; 81(13): 1079-84.
- 5. Yigitturk G, Acara AC, Erbas O, Oltulu F, Yavasoglu NUK, Uysal A, et al. The antioxidant role of agomelatine and gallic acid on oxidative stress in STZ induced type I diabetic rat testes. Biomed Pharmacother. 2017; 87: 240-6.
- 6. Alves MG, Martins AD, Rato L, Moreira PI, Socorro S, Oliveira PF. Molecular mechanisms beyond glucose transport in diabetes-related male infertility. Biochim Biophys Acta. 2013; 1832(5): 626-35.
- 7. Li CL, Chang L, Guo L, Zhao D, Liu HB, Wang QS, et al. β-elemene induces caspase-dependent apoptosis in human glioma cells in vitro through the upregulation of Bax and Fas/ FasL and downregulation of Bcl-2. Asian Pac J Cancer Prev. 2014; 15(23): 10407-12.
- 8. Sehgal V, Ram PT. Network Motifs in JNK Signaling. Genes Cancer. 2013; 4(9-10): 409-13.
- 9. Faid I, Al-Hussaini H, Kilarkaje N. Resveratrol alleviates diabetes-induced testicular dysfunction by inhibiting oxidative stress and c-Jun N-terminal kinase signaling in rats. Toxicol Appl Pharmacol. 2015; 289(3): 482-94.
- 10. Li J, Chen F, Chen Y, Wang Z. Mitochondrialand Fas-L-mediated pathways involved in quinestrol induced spermatogenic apoptosis in adult rat testes. Toxicol Mech Methods. 2014; 24(9): 609-15.
- 11. Bogoyevitch MA, Arthur PG. Inhibitors of c-Jun N-terminal kinases: JNK no more? Biochim Biophys Acta. 2008; 1784(1): 76-93.
- 12. Bennett BL, Sasaki DT, Murray BW, O'Leary EC, Sakata ST, Xu W, et al. SP600125, an anthrapyrazolone inhibitor of Jun N-terminal kinase. Proc Natl Acad Sci U S A. 2001; 98(24): 13681-6.
- 13. Zhou L, Yang Z, Lu X, Li X, An X, Chai J, Yang Q, Yan S, Li Y. JNK inhibitor alleviates apoptosis of fetal neural stem cells induced by emulsified isoflurane. Oncotarget. 2017; 8(55): 94009-19.
- 14. Shen H, Wu N, Wang Y, Han X, Zheng Q, Cai X, Zhang H, Zhao M. JNK inhibitor SP600125 attenuates paraquat-induced acute lung injury: an in vivo and in vitro study. Inflammation. 2017; 40(4): 1319-30.
- 15. Hong Z, Hong Z, Wu D, Nie H. Specific MAPK inhibitors prevent hyperglycemia-induced renal diseases in type 1 diabetic mouse model. Mol Cell Biochem. 2016; 419(1-2): 1-9.
- 16. Mili D, Abid K, Rjiba I, Kenani A. Effect of SP600125 on the mitotic spindle in HeLa Cells, leading to mitotic arrest, endoreduplication and apoptosis. Mol Cytogenet. 2016; 9: 86.
- 17. Al-Roujeaie AS, Abuohashish HM, Ahmed MM, Alkhamees OA. Effect of rutin on diabetic-induced erectile dysfunction: Possible involvement of testicular biomarkers in male rats. Andrologia. 2016; doi: 10.1111/and.12737.
- 18. Amaral S, Oliveira PJ, Ramalho-Santos J. Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species. Curr Diabetes Rev 2008;4(1):46-54.
- 19. Wada T, Penninger JM. Mitogen-activated protein kinases in apoptosis regulation. Oncogene. 2004; 23(16): 2838-49.
- 20. Qi S, Fu W, Wang C, Liu C, Quan C, Kourouma A, et al. BPA-induced apoptosis of rat Sertoli cells through Fas/FasL and JNKs/p38 MAPK pathways. Reprod Toxicol. 2014; 50: 108-16.
- 21. Aggarwal A, Misro MM, Maheshwari A, Sehgal N, Nandan D. N-acetylcysteine counteracts oxidative stress and prevents hCG-induced apoptosis in rat Leydig cells through down regulation of caspase-8 and JNK. Mol Reprod Dev. 2010; 77(10): 900-9.
- 22. Lee J, Richburg JH, Younkin SC, Boekelheide K. The Fas system is a key regulator of germ cell apoptosis in the testis. Endocrinology. 1997; 138(5): 2081-8.
- 23. Celik-Ozenci C, Sahin Z, Ustunel I, Akkoyunlu G, Erdogru T, Korgun ET, et al. The Fas system may have a role in male reproduction. Fertil Steril. 2006; 85: 1168-78.
- 24. Bayram S, Kizilay G, Topcu-Tarladacalisir Y. Evaluation of the Fas/FasL signaling pathway in diabetic rat testis. Biotech Histochem. 2016; 91(3): 204-11.
- 25. Shi Y, Song Y, Wang Y, Wang Y, Liang X, Hu Y, et al. beta-Benzene hexachloride induces apoptosis of rat Sertoli cells through generation of reactive oxygen species and activation of JNKs and FasL. Environ Toxicol. 2011; 26(2): 124-35.
- 26. Munshi A, Ramesh R. Mitogen-activated protein kinases and their role in radiation response. Genes Cancer. 2013; 4(9-10): 401-8.
- 27. Li LM, Liu QH, Qiao JT, Zhang C. Abeta(31- 35)-induced neuronal apoptosis is mediated by JNKdependent extrinsic apoptosis pathway. Neurosci Bull. 2009; 25(6): 361-6.
- 28. Bai M, Liu Y, Yin D, Zhang M, Wang Y, Ma X, et al. Inhibition of c-Jun N-terminal kinase signaling suppresses skin flap apoptosis in a rat ischemia and/or reperfusion model. J Surg Res. 2016; 206(2): 337-46.
- 29. Bao L, Zu J, He Q, Zhao H, Zhou S, Ye X, et al. Thrombin-induced apoptosis in neurons through activation of c-Jun-N-terminal kinase. Toxicol Mech Methods. 2017; 27(1): 18-23.
- 30. Moon DO, Kim MO, Kang CH, Lee JD, Choi YH, Kim GY. JNK inhibitor SP600125 promotes the formation of polymerized tubulin, leading to G2/M phase arrest, endoreduplication, and delayed apoptosis. Exp Mol Med.
- ISSN: 2822-4302
- Yayın Aralığı: Yılda 3 Sayı
- Başlangıç: 2017
- Yayıncı: -
Sayıdaki Diğer Makaleler
Hiperemezis Gravidarumlu Gebelerde Psikolojik Belirti Taraması
İsa Şükrü ÖZ, Ahmet Birtan BORAN, Güler ATEŞER, Besim Haluk BACANAKGİL, Sezgi Güllü YILDIRIM
Periferik Arter Hastalığında Asetilsalisilik Asit ve Klopidogrel Cevapsızlığı
Elif COŞKUN, Veli Yıldırım İMREN
Eren Göktuğ CEYLAN, Nur Şeyma BORAZAN, Ali CAN, Emre ÇALIŞKAN, Ömer Emre DOLU, Yasemin YAVUZ
İnci TURAN, Hale SAYAN ÖZAÇMAK, Figen BARUT, Veysel Haktan ÖZAÇMAK, Bülent UÇAN
Jnk İnhibisyonunun Diyabetik Testis Dokusundaki Fas/Fasl Sinyal Yolağına Etkileri
Gülnur KIZILAY, Şinasi BAYRAM, Onur ERSOY, Yeliz DÖNMEZ BOZDEMİR