Roles of interferon‐gamma and its target genes in schizophrenia: Proteomics‐based reverse genetics from mouse to human

Abstract

A decreased production of interferon gamma (IFNG) has been observed in acute schizophrenia. In order to explore the possible relationship between IFNG and schizophrenia, we attempted to analyze the differentially expressed proteins in the brains of interferon-gamma knockout (Ifng-KO) mice. Five upregulated and five downregulated proteins were identified with 2D gels and MALDI-TOF/TOF MS analyses in Ifng-KO mouse brain. Of the identified proteins, we focused on creatine kinase brain (CKB) and triose phosphate isomerase 1 (TPI1). Consistent with the proteomic data, reverse transcriptase-mediated PCR, immunoblotting, and immunohistochemistry analyses confirmed that the levels of gene expressions of Ckb and Tpi1 were downregulated and upregulated, respectively. When we analyzed the genetic polymorphisms of the single nucleotide polymorphisms (SNPs) of their human orthologous genes in a Korean population, the promoter SNPs of CKB and TPI1 were weakly associated with schizophrenia. In addition, IFNG polymorphisms were associated with schizophrenia. These results suggest that IFNG and proteins affected by IFNG may play a role in the pathogenesis of schizophrenia.

Cellular compartmentation of energy metabolism: creatine kinase microcompartments and recruitment of B-type creatine kinase to specific subcellular sites

“…Hearing loss in Huntington's disease may be directly related to dysfunctional Ca 2+ handling due to reduced BCK activity, resulting from either ROS-induced BCK damage or inhibition of BCK promoters by Huntingtin in the elderly (Lin et al 2011b;Lin et al 2013). BCK expression is highly regulated by various signals, including estrogens (Reiss and Kaye 1981), p53 (Zhao et al 1994), or interferon gamma (Kim et al 2012), and dysregulation is often seen in various pathologies, with cancer probably being the best studied (see the contribution by Yan 2016 in this issue). Although it remains a challenge to describe the molecular topology and function of microcompartments, including those of BCK, this will be essential to address the outstanding questions on their contribution to normal and pathological physiology and to envisage pharmacological interventions at a defined subcellular level.…”

Brain interference: Revisiting the role of IFNγ in the central nervous system

“…Accordingly, the potential neuropathological contributions of IFNg have not escaped attention. Polymorphisms in the IFNg gene and its receptor were recently associated with the development of schizophrenia (Jemli et al, 2016;H.J. Kim et al, 2012;Paul-Samojedny et al, 2011) and acute manifestations of the disease have been correlated with decreased levels of IFNg (Arolt et al, 2000).…”

15-Hydroxyprostaglandin dehydrogenase is upregulated by hydroxychloroquine in rheumatoid arthritis fibroblast-like synoviocytes

“…The tissue sections were then incubated with 3,3′-diaminobenzidine tetrahydro-chloride, containing 0.05% H 2 O 2 for 3 min and counterstained with hematoxylin. Image quantification was performed with Image J software (NIH, Bethesda, MD, USA), as previously described, with minor modifications ( 17 ). Briefly, the pixel intensities in the enlarged images (magnification, x200) were calibrated by setting the display value range from 0 (black) to 255 (red).…”