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(American Journal of Pathology. 2004;165:577-592.)
© 2004 American Society for Investigative Pathology

The 14-3-3 Protein Isoform Expressed in Reactive Astrocytes in Demyelinating Lesions of Multiple Sclerosis Binds to Vimentin and Glial Fibrillary Acidic Protein in Cultured Human Astrocytes

Jun-ichi Satoh^*, Takashi Yamamura^* and Kunimasa Arima

From the Department of Immunology,^* National Institute of Neuroscience, and the Department of Neuropathology, National Center Hospital for Mental, Nervous, and Muscular Disorders, National Center of Neurology and Psychiatry, Tokyo, Japan

The 14-3-3 protein family consists of acidic 30-kd proteins expressed at high levels in neurons of the central nervous system. Seven isoforms form a dimeric complex that acts as a molecular chaperone that interacts with key signaling components. Recent studies indicated that the 14-3-3 protein identified in the cerebrospinal fluid of various neurological diseases including multiple sclerosis (MS) is a marker for extensive brain destruction. However, it remains unknown whether the 14-3-3 protein plays an active role in the pathological process of MS. To investigate the differential expression of seven 14-3-3 isoforms in MS lesions, brain tissues of four progressive cases were immunolabeled with a panel of isoform-specific antibodies. Reactive astrocytes in chronic demyelinating lesions intensely expressed ß, , , , and isoforms, among which the isoform is a highly specific marker for reactive astrocytes. Furthermore, protein overlay, mass spectrometry, immunoprecipitation, and double-immunolabeling analysis showed that the 14-3-3 protein interacts with both vimentin and glial fibrillary acidic protein in cultured human astrocytes. These results suggest that the 14-3-3 protein plays an organizing role in the intermediate filament network in reactive astrocytes at the site of demyelinating lesions in MS.

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