Decreased expression of Fyn protein and disbalanced alternative splicing patterns in platelets from patients with schizophrenia
| Autor: | Kotaro Hattori, Shun Hamada, Tomoko Isosaka, Takeshi Yagi, Hiroshi Fukuzako, Yoji Murata, Tomo Hashiguchi, Shigeki Yuasa |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Blood Platelets Exonucleases Male Transcriptional Activation Psychosis medicine.medical_specialty Blotting Western Down-Regulation Gene Expression Biology Proto-Oncogene Proteins c-fyn environment and public health Inteins Mice Exon FYN Downregulation and upregulation Internal medicine Gene expression medicine Animals Humans Family RNA Messenger Phosphorylation Biological Psychiatry Reverse Transcriptase Polymerase Chain Reaction Kinase Alternative splicing hemic and immune systems medicine.disease Neoplasm Proteins Mice Inbred C57BL Alternative Splicing enzymes and coenzymes (carbohydrates) Psychiatry and Mental health Endocrinology embryonic structures Immunology Schizophrenia Female biological phenomena cell phenomena and immunity Signal transduction |
| Zdroj: | Psychiatry Research. 168:119-128 |
| ISSN: | 0165-1781 |
| DOI: | 10.1016/j.psychres.2008.04.014 |
| Popis: | Fyn, a Src-family kinase, is highly expressed in brain tissue and blood cells. In the mouse brain, Fyn participates in brain development, synaptic transmission through the phosphorylation of N-methyl-d-aspartate (NMDA) receptor subunits, and the regulation of emotional behavior. Recently, we found that Fyn is required for the signal transduction in striatal neurons that is initiated by haloperidol, an antipsychotic drug. To determine whether Fyn abnormalities are present in patients with schizophrenia, we analyzed Fyn expression in platelet samples from 110 patients with schizophrenia, 75 of the patients' first-degree relatives, and 130 control subjects. A Western blot analysis revealed significantly lower levels of Fyn protein among the patients with schizophrenia and their relatives, compared with the level in the control group. At the mRNA level, the splicing patterns of fyn were altered in the patients and their relatives; specifically, the ratio of fynDelta7, in which exon 7 is absent, was elevated. An expression study in HEK293T cells revealed that FynDelta7 had a dominant-negative effect on the phosphorylation of Fyn's substrate. These results suggest novel deficits in Fyn function, manifested as the downregulation of Fyn protein or the altered transcription of the fyn gene, in patients with schizophrenia. |
| Databáze: | OpenAIRE |
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