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Dysregulated ubiquitin proteasome system leads to neurodegeneration in a spontaneous obese rat model (559.1)
Author(s) -
Reddy G,
Reddy S,
Reddy V,
Raghu G,
Giridharan N
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.559.1
Subject(s) - neurodegeneration , proteasome , endoplasmic reticulum , ubiquitin , apoptosis , microbiology and biotechnology , endocrinology , biology , medicine , neuroscience , disease , biochemistry , gene
Objective: A spontaneously developed obese rat (WNIN/Ob) was established from the existing WNIN rats by selective breeding. The WNIN/Ob rats show accelerated aging and develop age related diseases including neurodegeneration. The main aim is to investigate the role of ubiquitin proteasome system (UPS) in obesity‐associated neurodegeneration in WNIN/Ob rat model. Methods: Various components of UPS like ubiquitin, UCHs (ubiquitin C‐terminal hydrolases), proteasomal sub‐units and endoplasmic reticulum (ER) stress markers were analysed by qRT‐PCR and immunoblotting. Chymotrypsin‐like activity of proteasome was assayed by fluorometric method. Apoptotis and morphology of neurons in the cerebral cortex was assessed by immunohistochemistry and transmission electron microscopy, respectively. Results: The results indicated dysregulated UPS, increased ER stress and up‐regulation of apoptotic regulators in obese rats. Neurons in the cerebral cortex of obese rats showed swollen mitochondria, disrupted ER and degenerating axons, nucleus and finally neurons. It appears UCHL‐1 mediated apoptosis through stabilizing p53 as a key factor of neurodegeneration. Conclusion: Alterations in the UPS may be causally related to neurodegeneration in WNIN‐obese rat. Further this rat model could be a suitable animal model for investigating the role of UPS in age related neurodegenerative diseases.