Mutations in the glycosyltransferase genes involved in glycolipid synthesis and disorders of the biosynthesis

Glycosphingolipids are composed of a hydrophobic ceramide portion, in which a fatty acid is bound to a long-chain base called sphingosine, and a hydrophilic sugar portion. Sialic acid-containing glycosphingolipids, called gangliosides, are abundant in the central nervous system, and four species GM1, GD1a, GD1b, and GT1b are predominant in mammalian brains. Both GM3 synthase and GM2/GD2 synthase are essential for the biosynthesis of these four major species. Pathogenic mutations in the genes encoding GM3 synthase（ST3GAL5）and GM2/GD2 synthase（B4GALNT1）are the cause of infantile-onset epilepsy syndrome associated with developmental regression as well as abnormal movements and blindness, and SPG26, a complicated form of hereditary spastic paraplegia associated with intellectual disability and peripheral neuropathy, respectively. In this review, the author summarizes the current understanding of the pathophysiology of glycolipid biosynthesis disorders based on the results of studies using gene knockout mice, and introduces the first cases of ST3GAL5 and B4GALNT1 gene mutations in Japan that have recently been identified in patients with neurological disorders.departmental bulletin pape

Summaries of Doctoral Theses

departmental bulletin pape

Bag1 protein loss sensitizes mouse embryonic fibroblasts to glutathione depletion

Bcl2-associated athanogene-1 protein (Bag1) acts as a co-chaperone of heat shock protein 70 and heat shock cognate 70 (HSP70/HSC70) and regulates multiple cellular processes, including cell proliferation, apoptosis, environmental stress response, and drug resistance. Since Bag1 knockout mice exhibited fetal lethality, the in vivo function of Bag1 remains unclear. In this study, we established a mouse line expressing Bag1 gene missing exon 5, which corresponds to an encoding region for the interface of HSP70/HSC70. Despite mice carrying homoalleles of the Bag1 mutant (Bag1Δex5) expressing undetectable levels of Bag1, Bag1Δex5 homozygous mice developed without abnormalities. Bag1Δex5 protein was found to be highly unstable in cells and in vitro. We found that the growth of mouse embryonic fibroblasts (MEFs) derived from Bag1Δex5-homo mice was attenuated by doxorubicin and a glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO). In response to BSO, Bag1Δex5-MEFs exhibited a higher dropping rate of GSH relative to the oxidized glutathione level. In addition, Bag1 might mitigate cellular hydrogen peroxide levels. Taken together, our results demonstrate that the loss of Bag1 did not affect mouse development and that Bag1 is involved in intracellular GSH homeostasis, namely redox homeostasis.journal articl

中表紙・目次

departmental bulletin pape

Regulatory mechanism of Focal-adhesion kinase on sialylation of N-glycans

東北医科薬科大学博士（薬科学）令和5年度doctoral thesi

Examining community-centred disaster trauma support and brainspotting

Thirteen years have passed since the Great East Japan Earthquake. The area around the Tohoku Medical and Pharmaceutical University Hospital has changed, showing that it is still in the process of reconstruction. The experience of the disaster is being passed on to the next generation. The psychological trauma of the disaster exists in the area. The author conducted research on visual psychological trauma and visual memory in the affected areas. The author also discussed ways to adapt psychological trauma support to the culture of the Tohoku region. Based on these findings, the author used brain spotting as a treatment for visual psychological trauma. In some cases, talk therapy cannot be adapted to local psychological trauma. Brain spotting as a treatment method for visual psychological trauma has the advantage of reassuring people living in the area.departmental bulletin pape

Deubiquitinase BRCC36 associates with FLT3-ITD to regulate its protein stability and intracellular signaling in acute myeloid leukemia

東北医科薬科大学博士（薬科学）令和5年度doctoral thesi

教育理念・奥付

departmental bulletin pape

The epidemiology of post-COVID-19 condition: a Japanese claim database study

Coronavirus disease 2019（COVID-19）is an ongoing pandemic, and COVID-19 infection has led to post-COVID-19 conditions. However, an analysis of post-COVID-19 conditions using a real-world database has not yet been reported in Japan. Using Japanese inpatient and outpatient claims databases, we evaluated patients with an ICD-10-CM code for post-COVID-19 condition（U09.9）between November 1, 2021, and May 31, 2023. The main outcome of this study was the symptoms in the same month after post-COVID-19 condition diagnosis. Of the 8,069 included outpatients with post-COVID-19 conditions, the median age of these patients was 54.0 years（interquartile range: 36.0−76.0 years）, with males including 50.1%. The patients were divided into three groups according to age: 486 patients aged 0−17 years, 4,512 patients aged 18−64 years, and 3,071 patients aged >65 years. The rates of post-COVID-19 conditions diagnosed in outpatient department were 72.6%. Among complications, respiratory complications（40.7%）were the largest number of complications in the same month of post-COVID-19 diagnosis, followed by sleep disorders（15.8%）, malaise and fatigue（7.3%）, and headache（7.1%）. In conclusion, we assessed the symptoms of post-COVID-19 conditions using a Japanese claims database. Additional follow-up studies using other data sources as databases are required.departmental bulletin pape

生体内分子の効率的な測定法の開発に関する研究

東北医科薬科大学博士（薬科学）令和5年度doctoral thesi