RGD Reference Report - Involvement of Src-suppressed C kinase substrate in experimental autoimmune encephalomyelitis: a link between release of astrocyte proinflammatory factor and oligodendrocyte apoptosis. - Rat Genome Database

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Involvement of Src-suppressed C kinase substrate in experimental autoimmune encephalomyelitis: a link between release of astrocyte proinflammatory factor and oligodendrocyte apoptosis.

Authors: Li, Xiaohong  Yan, Meijuan  Hu, Ling  Sun, Linlin  Zhang, Fupeng  Ji, Huoyan  Jiang, Jing  Wang, Ping  Liu, Haiou  Gao, Ying  Tao, Tao  He, Xingxin  Cheng, Chun  Shen, Aiguo 
Citation: Li X, etal., J Neurosci Res. 2010 Jul;88(9):1858-71. doi: 10.1002/jnr.22355.
RGD ID: 14348972
Pubmed: (View Article at PubMed) PMID:20155814
DOI: Full-text: DOI:10.1002/jnr.22355

Src-suppressed C kinase substrate (SSeCKS) is involved in inflammation in the central nervous system (CNS), and plays a role in control of cell signaling and cytoskeletal arrangement. However, the expression and function of SSeCKS and its function in multiple sclerosis (MS) and its common animal model, experimental autoimmune encephalomyelitis (EAE) remained to be elucidated. In the present study, we first reported that SSeCKS was remarkably increased in astrocytes of EAE rats in vivo. TNF-alpha and NO were significantly induced in astrocytes stimulated with LPS/IFN-gamma in vitro, which was blocked in astrocytes transfected with SSeCKS siRNA. These results indicated that SSeCKS played a role in the production of TNF-alpha and NO in astrocytes with inflammatory stimulation. As excessive release of TNF-alpha and NO were major mediators in autoimmune diseases and correlated with oligodendrocyte cell death, we further investigated whether SSeCKS participated in oligodendrocyte apoptosis. Conditioned media (CM) from astrocytes treated with LPS/IFN-gamma decreased oligodendrocyte cell viability, while siRNA targeted to SSeCKS in astrocytes inhibited oligodendrocyte cell death. The results from antibody neutralization and NO inhibition suggested that the oligodendrocyte apoptosis may be due to the production of astrocyte-derived proinflammatory factors (TNF-alpha and NO). These findings revealed that there was a pathogenic interaction between SSeCKS expression in astrocytes and oligodendrocyte apoptosis. Understanding the mechanism of SSeCKS in the pathogenesis of EAE may contribute to the development of new therapeutic strategies against EAE and MS.



Disease Annotations    

Gene Ontology Annotations    

Biological Process

Objects Annotated

Genes (Rattus norvegicus)
Akap12  (A-kinase anchoring protein 12)

Genes (Mus musculus)
Akap12  (A kinase (PRKA) anchor protein (gravin) 12)

Genes (Homo sapiens)
AKAP12  (A-kinase anchoring protein 12)


Additional Information