Proteomic analysis of lymphoblastoid cell lines from schizophrenic patients

Akira Yoshimi, Shinnosuke Yamada, Shohko Kunimoto, Branko Aleksic, Akihiro Hirakawa, Mitsuki Ohashi, Yurie Matsumoto, Kazuhiro Hada, Norimichi Itoh, Yuko Arioka, Hiroki Kiumura, Itaru Kushima, Yukako Nakamura, Tomoko Shiino, Daisuke Mori, Satoshi Tanaka, Shuko Hamada, Yukihiro Noda, Taku Nagai, Kiyofumi YamadaNorio Ozaki

Research output: Contribution to journalArticle

Abstract

Although a number of studies have identified several convincing candidate genes or molecules, the pathophysiology of schizophrenia (SCZ) has not been completely elucidated. Therapeutic optimization based on pathophysiology should be performed as early as possible to improve functional outcomes and prognosis; to detect useful biomarkers for SCZ, which reflect pathophysiology and can be utilized for timely diagnosis and effective therapy. To explore biomarkers for SCZ, we employed fluorescence two-dimensional differential gel electrophoresis (2D-DIGE) of lymphoblastoid cell lines (LCLs) (1st sample set: 30 SCZ and 30 CON). Differentially expressed proteins were sequenced by liquid chromatography tandem-mass spectrometry (LC-MS/MS) and identified proteins were confirmed by western blotting (WB) (1st and 2nd sample set: 60 SCZ and 60 CON). Multivariate logistic regression analysis was performed to identify an optimal combination of biomarkers to create a prediction model for SCZ. Twenty protein spots were differentially expressed between SCZ and CON in 2D-DIGE analysis and 22 unique proteins were identified by LC-MS/MS. Differential expression of eight of 22 proteins was confirmed by WB. Among the eight candidate proteins (HSPA4L, MX1, GLRX3, UROD, MAPRE1, TBCB, IGHM, and GART), we successfully constructed logistic regression models comprised of 4- and 6-markers with good discriminative ability between SCZ and CON. In both WB and gene expression analysis of LCL, MX1 showed reproducibly significant associations. Moreover, Mx1 and its related proinflamatory genes (Mx2, Il1b, and Tnf) were also up-regulated in poly I:C-treated mice. Differentially expressed proteins might be associated with molecular pathophysiology of SCZ, including dysregulation of immunological reactions and potentially provide diagnostic and prognostic biomarkers.

Original languageEnglish
Article number126
JournalTranslational psychiatry
Volume9
Issue number1
DOIs
Publication statusPublished - 01-12-2019
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Cellular and Molecular Neuroscience
  • Biological Psychiatry

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  • Cite this

    Yoshimi, A., Yamada, S., Kunimoto, S., Aleksic, B., Hirakawa, A., Ohashi, M., Matsumoto, Y., Hada, K., Itoh, N., Arioka, Y., Kiumura, H., Kushima, I., Nakamura, Y., Shiino, T., Mori, D., Tanaka, S., Hamada, S., Noda, Y., Nagai, T., ... Ozaki, N. (2019). Proteomic analysis of lymphoblastoid cell lines from schizophrenic patients. Translational psychiatry, 9(1), [126]. https://doi.org/10.1038/s41398-019-0461-2