The Role of Fas/Fasl Signaling Pathway In Diabetic Testicular Tissue by Administered Jnk Inhibition

Abstract

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.

Keywords

• Diabetes mellitus,Testis,SP600125,Fas,FasL,Caspase 8

Jnk İnhibisyonunun Diyabetik Testis Dokusundaki Fas/Fasl Sinyal Yolağına Etkileri

Abstract

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.

Keywords

• Diabetes mellitus,Testis,SP600125,Fas,FasL,Kaspaz 8

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