title: Increased expression of phosphorylated c-Jun and phosphorylated c-Jun N-terminal kinase associated with neuronal cell death in diabetic and high glucose exposed rat retinas.
abstract: The aim of this study is to examine whether the increased expression of phosphorylated c-Jun (p-c-Jun) and phosphorylated c-Jun N-terminal kinase (p-JNK) are significantly associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Retinas isolated from six adult male Sprague-Dawley rats and six streptozotocin-induced diabetic rats (DM) were cultured in serum-free medium. The explants from non-diabetic controls were cultured in normal-glucose (N) or high-glucose (HG) medium. Furthermore, neurotrophin-4 (NT-4) and Taurine-conjugated ursodeoxycholic acid (TUDCA) were incubated in HG medium. After 7 days, the numbers of regenerating neurites were counted per explant. After counting, the explants were fixed, cryosectioned, and stained by TUNEL, and also immunostained for p-c-Jun and p-JNK. The numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells in the GCL were significantly higher and the numbers of regenerating neurites were significantly lower in the HG and the DM groups than in the N groups. In the HG groups supplemented with NT-4 and TUDCA, the numbers of TUNEL-positive, p-c-Jun- and p-JNK-immunopositive cells were significantly lower and the numbers of neurites were significantly higher than in the HG group without NT-4 and TUDCA. Increased expression of p-c-Jun and p-JNK is associated with neuronal cell death in diabetic rat retinas and retinas exposed to high glucose. Neuroprotective effect of TUDCA and NT-4 is correlated with the suppression of p-c-Jun and p-JNK expression. These results provide a better understanding of the neurodegenerative process underlying DR.
authors: Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan. Electronic address: Tarii@aol.com.
authors: Toshiyuki
authors: T
authors: Oshitari
authors: Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Guzel
authors: G
authors: Bikbova
authors: Department of Ophthalmology and Visual Science, Chiba University Graduate School of Medicine, Chiba, Japan.
authors: Shuichi
authors: S
authors: Yamamoto
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D016923:Cell Death / Q000187:drug effects / Q000502:physiology*; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology*; D003930:Diabetic Retinopathy / Q000473:pathology / Q000503:physiopathology*; D005947:Glucose / Q000633:toxicity*; D066298:In Vitro Techniques; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D009414:Nerve Growth Factors / Q000494:pharmacology; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology; D016501:Neurites / Q000473:pathology / Q000502:physiology; D009474:Neurons / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010766:Phosphorylation; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D013311:Streptozocin; D013655:Taurochenodeoxycholic Acid / Q000494:pharmacology
chemical_list: D009414:Nerve Growth Factors; D018696:Neuroprotective Agents; D016755:Proto-Oncogene Proteins c-jun; D013655:Taurochenodeoxycholic Acid; D013311:Streptozocin; C031655:ursodoxicoltaurine; D048031:JNK Mitogen-Activated Protein Kinases; D005947:Glucose; C073922:neurotrophin 4
keywords: Diabetic retinas; Endoplasmic reticulum stress; High glucose; Neurotrophin-4; c-Jun; c-Jun N-terminal kinase