一般ポスター

一般ポスターストレス応答

7月8日（土）　12:50-13:50　ポスター会場① 3P①-1 グリア細胞におけるER-Golgi SNAREの発現とβAPPのプロセシングに対するER/ゴルジストレスの影響 Effect of ER/Golgi stress on the expression of ER-Golgi SNARE proteins and βAPP processing in glial cells 須賀　圭^1,2, 山本－土方　幸子¹, 寺尾　安生², 丑丸　真¹ 1. 杏林大　医　化学, 2. 杏林大　医　病態生理 Kei Suga^1,2, Sachiko Yamamoto-Hijikata¹, Yasuo Terao², Makoto Ushimaru¹ 1. Dept. Chem. Kyorin Univ., Faculty of Med., Tokyo, Japan, 2. Dept. Med. Physiol. Kyorin Univ., Faculty of Med., Tokyo, Japan Involvement of the dysfunction of neuronal cells caused by ER/Golgi stress in neurodegenerative diseases such as Alzheimer’s disease (AD) is poorly understood. We have been focusing on the function of ER-Golgi SNAREs in βAPP processing under cellular stress. We previously showed that ER/Golgi stress upregulate de novo synthesis of ER-Golgi SNAREs, and the reduction of β-amyloid peptide (Aβ peptide) secretion in neuronal cells. Conversely, down regulation of Syx5 protein was observed upon apoptosis which was due to the degradation by activated Caspase3. We have been utilizing primary cultured neurons and neuroblastoma cell lines to see whether the organelle stress-induced changes in neurons are responsible for the aberrant processing of βAPP under the pathogenesis of sporadic type of AD. Our results implicated that the upregulation of ER-Golgi SNARE was associated with the protective effect on altered processing of βAPP under organelle stress and also on the subsequent apoptotic cell death caused by sustained stress. However, we did not know whether glial cells also respond to ER/Golgi stress and affect the expression of ER-Golgi SNARE and modify the βAPP processing. To understand the protective mechanism of ER-Golgi SNAREs in CNS, we performed western blotting, and ELISA analyses in stress-induced glial cells. We will present these data and would like to discuss the results.		7月8日（土）　12:50-13:50　ポスター会場① 3P①-2 小胞体タンパク質Derlin-1は成体海馬の神経幹細胞集団を維持する An endoplasmic reticulum protein Derlin-1 maintains neural stem cell populations in the adult hippocampus 村尾　直哉, 西頭　英起宮崎大学　医学部　機能生化学 Naoya Murao, Hideki Nishitoh Lab. of Biochem. and Mol. Biol., Fac. of Med., Univ. of Miyazaki, Japan An endoplasmic reticulum (ER) has a quality control mechanism that ER resident stress sensors recognize unfolded or misfolded proteins and trigger the unfolded protein response. A collapse of the ER quality control mechanism contributes to the onset and deterioration of several neurological disorders associated with impaired learning and memory. Adult neurogenesis in the hippocampal dentate gyrus plays an important role in learning and memory formation, and its homeostasis is disrupted in several neurological disorders associated with memory impairment. An ER membrane protein Derlin-1 is known to be important for ER quality control mechanisms. In this study, we show that disruption of ER homeostasis in adult neural stem cells (aNSCs) by loss of Derlin-1 results in abnormal adult neurogenesis and depletion of the NSC pool. Furthermore, as a candidate factor causing depletion of NSC pool due to deficiency of Derlin-1, we found that the protein expression of signal transducer and activator of transcription 5b (Stat5b) was decreased in Derlin-1-deficient aNSCs. In addition, disruption of aNSC homeostasis due to Derlin-1 deficiency was rescued by Stat5b expression in the dentate gyrus. In this presentation, we will discuss the detail of homeostatic abnormalities of aNSCs and their mechanisms.

7月8日（土）　12:50-13:50　ポスター会場① 3P①-3 コレステロール合成に着目した神経変性に対するケミカルシャペロンの作用メカニズム Chemical chaperones ameliorate neurodegeneration via improvement of cholesterol biosynthesis 杉山　崇史^1,2, 村尾　直哉², 西頭　英起² 1. 宮崎大学医学部附属病院　脳神経内科, 2. 宮崎大学医学部　機能制御学講座機能生化学分野 Takashi Sugiyama^1,2, Naoya Murao², Hideki Nishitoh² 1. Dept. of Neurology, Fac. of Med., Univ. of Miyazaki Hosp., Miyazaki, Japan There are no available therapies targeting the underlying molecular mechanisms of neurodegenerative diseases. Although chaperone therapies that alleviate endoplasmic reticulum (ER) stress recently showed promise in the treatment of neurodegenerative diseases, the detailed mechanisms remain unclear. We previously reported that mice with central nervous system-specific deletion of Derlin-1, which encodes an essential component for ER quality control, are useful as models of neurodegenerative diseases such as spinocerebellar degeneration. Cholesterol biosynthesis is essential for brain development, and its disruption inhibits neurite outgrowth, causing brain atrophy. In this study, we report a novel mechanism by which chemical chaperones ameliorate brain atrophy and motor dysfunction. ER stress was induced in the cerebella of Derlin-1 deficiency mice, whereas the administration of a chemical chaperone did not alleviate ER stress. However, chemical chaperone treatment ameliorated cholesterol biosynthesis impairment through SREBP-2 activation and simultaneously relieved brain atrophy and motor dysfunction. Altogether, these findings demonstrate that ER stress may not be the target of action of chaperone therapies and that chemical chaperone-mediated improvement of brain cholesterol biosynthesis is a promising novel therapeutic strategy for neurodegenerative diseases.		7月8日（土）　12:50-13:50　ポスター会場① 3P①-4 膠芽腫における核膜ストレス応答制御の分子機構 Molecular mechanism that drives differential response to Nuclear Envelope Stress in Glioblastoma Cell Lines 呉　祖倩, 上川　泰直, 齋藤　敦, 今泉　和則広島大学大学院医系科学研究科分子細胞情報学 Zuqian Wu, Yasunao Kamikawa, Atsushi Saito, Kazunori Imaizumi Department of Biochemistry, Institute of Biomedical & Health Sciences, Hiroshima University The nuclear envelope (NE) separates the nucleus from the cytoplasm. The NE is damaged by various cellular stresses such as constricted migration through narrow space, leading to the rupture of the NE. The cellular stresses that disrupt structure and function of the NE is known as NE stress. Recent studies have reported that NE stress is involved in some neurodegenerative disorders. It has also been suggested that NE stress is related to cancer malignancy by inducing DNA damage. However, the molecular mechanism underlying NE stress response remains unclear. Here, we investigated NE stress response in several cell lines derived from different types of cancers. A cell line derived from glioblastoma (GBM), U251MG exhibited severe nuclear deformation and DNA damage upon mechanical NE stress. In contrast, U87MG, another cell line derived from GBM showed neither severe nuclear deformation nor DNA damage. Previous studies have revealed that most NE rupture is repaired by the factors involved in the regulation of NE structure. We found that amount of a NE repair factor VPS4B is significantly lower in U251MG than in U87MG. In addition, the post-translational modification (PTM) of emerin, which is also involved in NE repair, is observed only in U251MG. These results indicate that differential expression of VPS4B and PTM of emerin contribute to cell type-specific NE stress response.

7月8日（土）　12:50-13:50　ポスター会場① 3P①-5 前障ストレス応答性神経細胞のマーカー遺伝子の同定 Identification of marker genes for claustral stress-responsive neurons 大久保　仁¹, 田沼　将人¹, 横山　泰久¹, 橋本　均^1,2,3,4, 笠井　淳司¹ 1. 大阪大院・薬・神経薬理, 2. 大阪大院・連合小児, 3. 大阪大・データビリティフロンティア機構, 4. 大阪大・先導的学際研究機構 Jin Ohkubo¹, Masato Tanuma¹, Yoshihisa Yokoyama¹, Hitoshi Hashimoto^1,2,3,4, Atsushi Kasai¹ 1. Lab. Mol. Neuropharmacol., Grad. Sch. Pharmaceut. Sci., Osaka Univ., 2. United Grad. Sch. Child Dev., Osaka Univ., 3. Inst. Datability Sci., Osaka Univ., 4. Inst. for Open Transdisciplinary Res. Initiatives, Osaka Univ. The claustrum (CLA) is a subcortical thin sheet structure, whose function is proposed to regulate saliency detection and attention allocation. A recent study shows that CLA neurons can be classified into core and shell subtypes with different gene expression patterns. We have previously shown that an excitatory CLA ensemble mediates stress-induced anxiety responses. However, the molecular definition of the stress-responsive CLA ensemble remains unknown. To address this, here we first performed single-cell RNA sequencing analysis of stress-responsive or non-responsive excitatory neurons in the CLA. By performing clustering analysis of all the collected neurons, two clusters with gene expression patterns corresponding to core and shell subtypes were obtained. Differential gene expression analysis revealed that Car12 expression was significantly upregulated in stress-responsive neurons in both clusters. In addition, to determine whether Car12-positive cells in the CLA are activated after exposure to stress, we performed double-color fluorescence in situ hybridization for Car12 and either a CLA marker Gnb4 or an immediate early gene Arc. More than three-quarters of Car12-positive cells expressed Gnb4 mRNA; over 80% of Car12-positive cells expressed Arc mRNA one hour after stress exposure. These findings suggest that Car12 is a marker gene for stress-responsive CLA neurons.