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

Year 2017, Volume: 1 Issue: 3, 112 - 118, 29.12.2017

Gülnur Kızılay Şinasi Bayram Onur Ersoy Yeliz Dönmez Bozdemir

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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