The Journal of Biochemistry最新文献

New insights into the regulation and roles of phosphatidylinositol 3,4-bisphosphate 对 3,4-二磷酸磷脂酰肌醇的调节和作用的新认识

The Journal of Biochemistry Pub Date : 2024-09-14 DOI: 10.1093/jb/mvae063

Junya Hasegawa

引用次数: 0

The NRF2 inducer CDDO-2P-Im provokes a reduction in amyloid β levels in Alzheimer’s disease model mice NRF2 诱导剂 CDDO-2P-Im 可降低阿尔茨海默病模型小鼠的淀粉样蛋白 β 水平

The Journal of Biochemistry Pub Date : 2024-09-11 DOI: 10.1093/jb/mvae060

Akira Uruno, Shiori Kadoguchi-Igarashi, Ritsumi Saito, Shohei Koiso, Daisuke Saigusa, Ching-Tung Chu, Takafumi Suzuki, Takashi Saito, Takaomi C Saido, Antonio Cuadrado, Masayuki Yamamoto

{"title":"The NRF2 inducer CDDO-2P-Im provokes a reduction in amyloid β levels in Alzheimer’s disease model mice","authors":"Akira Uruno, Shiori Kadoguchi-Igarashi, Ritsumi Saito, Shohei Koiso, Daisuke Saigusa, Ching-Tung Chu, Takafumi Suzuki, Takashi Saito, Takaomi C Saido, Antonio Cuadrado, Masayuki Yamamoto","doi":"10.1093/jb/mvae060","DOIUrl":"https://doi.org/10.1093/jb/mvae060","url":null,"abstract":"Alzheimer’s disease (AD) is the most common etiology of dementia. The transcription factor NF-E2-related factor 2 (NRF2) induces the expression of genes encoding phase II detoxification and antioxidant genes. NRF2 is regulated by Kelch-like ECH-associated protein 1 (KEAP1), and the KEAP1-NRF2 system is the key regulatory system involved in cytoprotection. To examine whether pharmacological induction of NRF2 expression alleviates AD phenotypes in vivo, we employed two AD mouse models, i.e., App NL-G-F/NL-G-F (AppNLGF) and APPV717I::TAUP301L (APP/TAU) mice. As the synthetic oleanane triterpenoid 1-[2-cyano-3,12-dioxooleana-1,9(11-dien-28-oyl)] (CDDO)-4(-pyridin-2-yl)-imidazole (CDDO-2P-Im) exhibits strong NRF2-inducing activity, we treated AD model mice with CDDO-2P-Im. We found that Aβ42 levels were markedly greater in the brains of AppNLGF mice than in those of APP/TAU mice. CDDO-2P-Im treatment significantly decreased Aβ42 levels, but not Aβ40 levels, in APP/TAU mice. Consequently, CDDO-2P-Im also decreased the ratio of Aβ42/Aβ40, a vital marker of amyloid plaque formation. LC–MS/MS analyses revealed that CDDO-2P-Im was delivered to the brains of the APP/TAU mice. CDDO-2P-Im induced the expression of detoxification and antioxidant gene targets of NRF2 and elevated reduced glutathione (GSH) levels in the mouse brain. These results support the notion that CDDO-2P-Im ameliorates AD-related pathologic changes.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142207457","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Cancer-associated SF3B1 Mutations Inhibit mRNA Nuclear Export by Disrupting SF3B1–THOC5 Interactions 癌症相关 SF3B1 突变通过破坏 SF3B1-THOC5 相互作用抑制 mRNA 核输出

The Journal of Biochemistry Pub Date : 2024-09-11 DOI: 10.1093/jb/mvae061

Gang Liu, Bo Zhao, Yueru Shi, Youzhong Wan

引用次数: 0

Mtc6/Ehg2 is a novel endoplasmic reticulum-resident glycoprotein essential for high-pressure tolerance Mtc6/Ehg2是一种新型内质网驻留糖蛋白，对耐受高压至关重要

The Journal of Biochemistry Pub Date : 2024-04-15 DOI: 10.1093/jb/mvae035

Satoshi Uemura, Takahiro Mochizuki, Yusuke Kato, Tetsuo Mioka, Riseko Watanabe, Mai Fuchita, Mao Yamada, Yoichi Noda, Takashi Moriguchi, Fumiyoshi Abe

{"title":"Mtc6/Ehg2 is a novel endoplasmic reticulum-resident glycoprotein essential for high-pressure tolerance","authors":"Satoshi Uemura, Takahiro Mochizuki, Yusuke Kato, Tetsuo Mioka, Riseko Watanabe, Mai Fuchita, Mao Yamada, Yoichi Noda, Takashi Moriguchi, Fumiyoshi Abe","doi":"10.1093/jb/mvae035","DOIUrl":"https://doi.org/10.1093/jb/mvae035","url":null,"abstract":"Hydrostatic pressure is a common mechanical stressor that modulates metabolism and reduces cell viability. Eukaryotic cells have genetic programs to cope with hydrostatic pressure stress and maintain intracellular homeostasis. However, the mechanism underlying hydrostatic pressure tolerance remains largely unknown. We have recently demonstrated that Maintenance of telomere capping protein 6 (Mtc6) plays a protective role in the survival of the budding yeast Saccharomyces cerevisiae under hydrostatic pressure stress by supporting the integrity of nutrient permeases. The current study demonstrate that Mtc6 acts as an endoplasmic reticulum (ER) membrane protein. Mtc6 comprises two transmembrane domains, a C-terminal cytoplasmic domain, and a luminal region with 12 Asn (N)-linked glycans attached to it. Serial mutational analyses showed that the cytoplasmic C-terminal amino acid residues GVPS are essential for Mtc6 activity. Multiple N-linked glycans in the luminal region are involved in the structural conformation of Mtc6. Moreover, deletion of MTC6 led to increased degradation of the leucine permease Bap2 under hydrostatic pressure, suggesting that Mtc6 facilitates proper folding of nutrient permeases in the ER under the stress condition. We propose a novel model of molecular function in which the glycosylated luminal domain and cytoplasmic GVPS sequences of Mtc6 cooperatively support the nutrient permease activity.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation of the cyclic single-chain Fv antibody derived from nivolumab by biophysical analyses and in vitro cell-based bioassay 通过生物物理分析和体外细胞生物测定评估由 nivolumab 衍生的环状单链 Fv 抗体

The Journal of Biochemistry Pub Date : 2024-04-09 DOI: 10.1093/jb/mvae034

Sena Kamesawa, Mizuki Ogawa, Yoshiki Funakoshi, Masaya Kato, Shosei Kai, Mana Namikawa, Kyo Okazaki, Takashi Sato, Yoshihiro Kobashigawa, Hiroshi Morioka

{"title":"Evaluation of the cyclic single-chain Fv antibody derived from nivolumab by biophysical analyses and in vitro cell-based bioassay","authors":"Sena Kamesawa, Mizuki Ogawa, Yoshiki Funakoshi, Masaya Kato, Shosei Kai, Mana Namikawa, Kyo Okazaki, Takashi Sato, Yoshihiro Kobashigawa, Hiroshi Morioka","doi":"10.1093/jb/mvae034","DOIUrl":"https://doi.org/10.1093/jb/mvae034","url":null,"abstract":"Single-chain Fv (scFv) is a recombinant small antibody in which a polypeptide linker connects the variable regions of the light chain (VL) and the heavy chain (VH). The practical use of scFv, however, has been prevented by its tendency to aggregate due to interchain VL–VH interactions. We recently developed a cyclic scFv whose N-terminus and C-terminus were connected by protein ligation techniques. Biophysical comparisons between cyclic and linear scFv have been conducted, but cell biological evaluations remain unexplored. Here we studied the properties of cyclic and linear scFv derived from nivolumab. Biophysical studies revealed that the thermal stability was not changed but that the antigen-binding activity was approximately 3-fold higher as a result of circularization. A cell-based PD-1/PD-L1 interaction inhibitory assay revealed that the biological activity of scFv was markedly higher in the circularized form. In addition, biophysical analysis of scFv proteins incubated in the presence of serum revealed that circularization suppressed the decrease in antigen-binding activity. It could be assumed that circularization of scFv improved stability in the presence of serum, which in turn would suggest the applicability of cyclic scFv as a biopharmaceutical format.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140598240","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Reflection 反射

The Journal of Biochemistry Pub Date : 2022-09-01 DOI: 10.1093/jb/mvac038

Akira Kikuchi

引用次数: 0

OUP accepted manuscript OUP接受稿件

The Journal of Biochemistry Pub Date : 2021-01-01 DOI: 10.1093/jb/mvab138

引用次数: 0

Crystal structure of metagenomic &bgr;-xylosidase/ &agr;-L-arabinofuranosidase activated by calcium 钙活化的宏基因组&bgr;-木糖苷酶/ &agr;- l -阿拉伯糖醛酸苷酶的晶体结构

The Journal of Biochemistry Pub Date : 2017-09-01 DOI: 10.1093/jb/mvx012

T. Matsuzawa, S. Kaneko, N. Kishine, Z. Fujimoto, K. Yaoi

{"title":"Crystal structure of metagenomic &bgr;-xylosidase/ &agr;-L-arabinofuranosidase activated by calcium","authors":"T. Matsuzawa, S. Kaneko, N. Kishine, Z. Fujimoto, K. Yaoi","doi":"10.1093/jb/mvx012","DOIUrl":"https://doi.org/10.1093/jb/mvx012","url":null,"abstract":"The crystal structure of metagenomic β-xylosidase/α-l-arabinofuranosidase CoXyl43, activated by calcium ions, was determined in its apo and complexed forms with xylotriose or l-arabinose in the presence and absence of calcium. The presence of calcium ions dramatically increases the kcat of CoXyl43 for p-nitrophenyl β-d-xylopyranoside and reduces the Michaelis constant for p-nitrophenyl α-l-arabinofuranoside. CoXyl43 consists of a single catalytic domain comprised of a five-bladed β-propeller. In the presence of calcium, a single calcium ion was observed at the centre of this catalytic domain, behind the catalytic pocket. In the absence of calcium, the calcium ion was replaced with one sodium ion and one water molecule, and the positions of these cations were shifted by 1.3 Å. The histidine-319 side chain, which coordinates to the 2-hydroxyl oxygen atom of the bound xylose molecule in the catalytic pocket, also coordinates to the calcium ion, but not to the sodium ion. The calcium-dependent increase in activity appears to be caused by the structural change in the catalytic pocket induced by the tightly bound calcium ion and coordinating water molecules, and by the protonation state of glutamic acid-268, the catalytic acid of the enzyme. Our findings further elucidate the complex relationship between metal ions and glycosidases.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79373760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 13

Giardia duodenalis Rad52 protein: biochemical characterization and response upon DNA damage 十二指肠贾第虫Rad52蛋白的生化特性及其对DNA损伤的响应

The Journal of Biochemistry Pub Date : 2017-08-01 DOI: 10.1093/jb/mvx009

Rosa María Martínez-Miguel, Antonio Sandoval-Cabrera, M. L. Bazán-Tejeda, A. L. Torres-Huerta, Diego A. Martínez-Reyes, R. Bermúdez-Cruz

{"title":"Giardia duodenalis Rad52 protein: biochemical characterization and response upon DNA damage","authors":"Rosa María Martínez-Miguel, Antonio Sandoval-Cabrera, M. L. Bazán-Tejeda, A. L. Torres-Huerta, Diego A. Martínez-Reyes, R. Bermúdez-Cruz","doi":"10.1093/jb/mvx009","DOIUrl":"https://doi.org/10.1093/jb/mvx009","url":null,"abstract":"Giardia duodenalis is a flagellated binucleated protozoan that colonizes the small intestine in mammals, causing giardiasis, acute or chronic diarrhea. DNA double strand break either endogenously or exogenously generated is a major insult to DNA and its repair by homologous recombination (HR) is crucial for genomic stability. During HR, Rad52 plays key roles in the loading of the Rad51 recombinase, and the annealing of the second double-strand break end to the displaced strand of the D-loop structure. Among the functions found in vitro in yeast and human Rad52 protein are: ssDNA or dsDNA binding activity, ability to anneal bare or RPA coated-ssDNA, as well as multimeric ring formation. In this work, we searched for conserved domains in a putative Rad52 protein from G. duodenalis (GdRad52). Its coding sequence was cloned, expressed and purified to study its biochemical properties. rGdRad52 binds to dsDNA and ssDNA, with greater affinity for the latter. Likewise, rGdRad52 promotes annealing of DNA uncoated and coated with GdRPA1. rGdRad52 interacts with GdDMC1B and with GdRPA1 protein as shown in far western blotting assay. Additionally, rGdRad52 formed multimeric rings as observed by electronic microscopy. Finally, GdRad52 is over expressed in response upon DNA damage inflicted on trophozoites.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87154861","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 4

GPNMB promotes proliferation of developing eosinophils GPNMB促进发育中的嗜酸性粒细胞增殖

The Journal of Biochemistry Pub Date : 2017-08-01 DOI: 10.1093/jb/mvx002

S. Hwang, J. Kang, B. K. Kim, Tae Gi Uhm, Hye Jeong Kim, Hyune-Hwan Lee, B. Binas, I. Chung

{"title":"GPNMB promotes proliferation of developing eosinophils","authors":"S. Hwang, J. Kang, B. K. Kim, Tae Gi Uhm, Hye Jeong Kim, Hyune-Hwan Lee, B. Binas, I. Chung","doi":"10.1093/jb/mvx002","DOIUrl":"https://doi.org/10.1093/jb/mvx002","url":null,"abstract":"Glycoprotein non-metastatic melanoma protein B (GPNMB) is a type I transmembrane protein that is expressed in a wide variety of cell types, including haematopoietic lineages. We previously demonstrated that GPNMB is one of the most highly expressed genes at an early and intermediate stage of eosinophil development. We herein examined GPNMB expression and its possible functional effect using cord blood (CB) CD34+ haematopoietic stem cells differentiating toward eosinophils during a 24-day culture period. Western blot and confocal microscopy analyses showed that GPNMB reached its highest levels at day 12 with most GPNMB-positive cells also expressing major basic protein 1 (MBP1), an eosinophil granule protein. GPNMB declined thereafter, but was still present at an appreciable level at day 24, the time when CB eosinophils most abundantly expressed MBP1 and were thus considered fully differentiated. When the developing CB cells were cultured in the presence of a blocking anti-GPNMB antibody, cell proliferation was significantly reduced. In agreement, ectopic expression of GPNMB in heterologous cells resulted in a significant increase in cell proliferation, while small interfering RNA of GPNMB inhibited the GPNMB-mediated proliferation. Thus, GPNMB is expressed in a temporal manner during eosinophil development and delivers a proliferative signal upon activation.","PeriodicalId":22605,"journal":{"name":"The Journal of Biochemistry","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2017-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75881387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 2