{"title":"Biochemical characterizations of the central fragment of human Reelin and identification of amino acid residues involved in its secretion.","authors":"Takao Kohno, Ikuma Nakagawa, Airi Taniguchi, Fang Heng, Mitsuharu Hattori","doi":"10.1093/jb/mvae058","DOIUrl":"10.1093/jb/mvae058","url":null,"abstract":"<p><p>Secreted protein Reelin is implicated in neuropsychiatric disorders and its supplementation ameliorates neurological symptoms in mouse disease models. Recombinant human Reelin protein may be useful for the treatment of human diseases, but its properties remain uncharacterized. Here, we report that full-length human Reelin was well secreted from transfected cells and was able to induce Dab1 phosphorylation. Unexpectedly, the central fragment of human Reelin was much less secreted than that of mouse Reelin. Three residues in the sixth Reelin repeat contributed to the secretion inefficiency, and their substitutions with mouse residues increased the secretion without affecting its biological activity. Our findings help efficient production of human Reelin protein for the supplementation therapy.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"385-393"},"PeriodicalIF":2.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142017584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Dietary methionine functions in proliferative zone maintenance and egg production via sams-1 in Caenorhabditis elegans.","authors":"Keiko Hirota, Rieko Yamauchi, Mai Miyata, Mariko Kojima, Koichiro Kako, Akiyoshi Fukamizu","doi":"10.1093/jb/mvae054","DOIUrl":"10.1093/jb/mvae054","url":null,"abstract":"<p><p>The maintenance of germ cells is critical for the prosperity of offspring. The amount of food consumption is known to be closely related to reproduction, i.e. the number of eggs decreases under calorie-restricted conditions in various organisms. Previous studies in Caenorhabditis elegans have reported that calorie restriction reduces the number of eggs and the reduction can be rescued by methionine. However, the effect of methionine on the reproductive process has not been fully understood. In this study, to assess the gonadal function of methionine metabolism, we firstly demonstrated that a depletion in dietary methionine resulted in reduced levels of S-adenosyl-l-methionine (SAM) and S-adenosyl homocysteine in wild-type N2, but not in glp-1 mutants, which possess only a few germ cells. Second, we found no recovery in egg numbers upon methionine administration in SAM synthase (sams)-1 mutants. Furthermore, a reduced number of proliferative zone nuclei exhibited in the sams-1 mutants was not rescued via methionine. Thus, our results have shown that dietary methionine is required for the normal establishment of both the germline progenitor pool and fecundity, mediated by sams-1.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"359-367"},"PeriodicalIF":2.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141751760","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomoki Ishiguro, Mariko Noda, Masashi Nishikawa, Koh-Ichi Nagata, Hidenori Ito
{"title":"Variations associated with neurodevelopmental disorders affect ARF1 function and cortical development.","authors":"Tomoki Ishiguro, Mariko Noda, Masashi Nishikawa, Koh-Ichi Nagata, Hidenori Ito","doi":"10.1093/jb/mvae053","DOIUrl":"10.1093/jb/mvae053","url":null,"abstract":"<p><p>ADP-ribosylation factors (ARFs) are a family of small GTPases that regulate vesicle trafficking and actin dynamics in cells. Recent genetic analyses have revealed associations between variations in ARF genes and neurodevelopmental disorders, although their pathophysiological significance remains unclear. In this study, we conducted biochemical, cell biological and in vivo analyses of ARF1 variants linked to neurodevelopmental disorders. The mant-GDP dissociation assay revealed that ARF1-p.R19C, -p.F51L, -p.R99C and -p.R99H exhibit higher GDP/GTP exchange activity compared to ARF1 wild type (WT). The GTPase-activating protein (GAP) increased the GTPase activity of WT, p.R19C, p.Y35H, p.F51L, p.P131L and p.P131R, but not of p.Y35D, p.T48I, p.R99C and p.R99H. The transient expression of p.R99C, p.R99H and p.K127E in mammalian cells resulted in the disruption of the Golgi apparatus. In utero electroporation-mediated gene transfer into the cortical neurons of embryonic mice demonstrated that p.R99C, p.R99H and p.K127E cause a migration defect. Expression of these variants resulted in the expansion of the Golgi apparatus in migrating cortical neurons. These findings suggest that the ARF1 variants linked to neurodevelopmental disorders, specifically p.R99C, p.R99H and p.K127E, disrupt the structure of the Golgi apparatus, thereby leading to a developmental defect of cortical neurons.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"347-357"},"PeriodicalIF":2.1,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141758961","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Molecular mechanisms of mechanosensing and plasticity of tendons and ligaments.","authors":"Takahide Matsushima, Asahara Hiroshi","doi":"10.1093/jb/mvae039","DOIUrl":"10.1093/jb/mvae039","url":null,"abstract":"<p><p>Tendons and ligaments, crucial components of the musculoskeletal system, connect muscles to bones. In the realm of sports, tendons and ligaments are vulnerable tissues, with injuries such as Achilles tendon rupture and anterior cruciate ligament tears directly impacting an athlete's career. Furthermore, repetitive trauma and tissue degeneration can lead to conditions like secondary osteoarthritis, ultimately affecting the overall quality of life. Recent research highlights the pivotal role of mechanical stress in maintaining homeostasis within tendons and ligaments. This review delves into the latest insights on the structure of tendons and ligaments and the plasticity of tendon tissue in response to mechanical loads.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"263-269"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11444931/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140903924","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Smitha Honnalagere Mallanna, Rajesh K Thimmulappa, Nandini D Chilkunda
{"title":"Dyslipidemia and hyperglycemia induce overexpression of Syndecan-3 in erythrocytes and modulate erythrocyte adhesion.","authors":"Smitha Honnalagere Mallanna, Rajesh K Thimmulappa, Nandini D Chilkunda","doi":"10.1093/jb/mvae050","DOIUrl":"10.1093/jb/mvae050","url":null,"abstract":"<p><p>Erythrocytes are important vascular components that play vital roles in maintaining vascular homeostasis, in addition to carrying oxygen. Previously, we reported that the changes in the internal milieu (e.g. hyperglycemia or hypercholesterolemia) increase erythrocyte adhesion to various extracellular matrix components, potentially through altering glycosaminoglycans (GAGs). In this study, we have investigated the expression of syndecan (Sdc) family members that could be involved in mediating cytoadherence under conditions of dyslipidemia and hyperglycemia. Among the Sdc family members analysed, we found significant overexpression of Sdc-3 in erythrocyte membranes harvested from high-fat-fed control and diabetic animals. Animal studies revealed a positive correlation between Sdc-3 expression, blood sugar levels and erythrocyte adhesion. In the human study, diabetic cohorts with body mass index >24.9 showed significantly increased expression of Sdc-3. Interestingly, blocking the Sdc-3 moiety with an anti-Sdc-3 antibody revealed that the core protein might not be directly involved in erythrocyte adhesion to fibronectin despite the GAGs bringing about adhesion. Lastly, Nano liquid chromatography-mass spectrometry/MS verified the presence of Sdc-3 in erythrocyte membranes. In conclusion, the high-fat diet and diabetes modulated Sdc-3 expression in the erythrocyte membrane, which may alter its adhesive properties and promote vascular complications.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"289-298"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498151","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Spatial heterogeneity and functional zonation of living tissues and organs in situ.","authors":"Yu Miyamoto, Masaru Ishii","doi":"10.1093/jb/mvae049","DOIUrl":"10.1093/jb/mvae049","url":null,"abstract":"<p><p>In most organs, resources such as nutrients, oxygen and physiologically active substances are unevenly supplied within the tissue spaces. Consequently, different tissue functions are exhibited in each space. This spatial heterogeneity of tissue environments arises depending on the spatial arrangement of nutrient vessels and functional vessels, leading to continuous changes in the metabolic states and functions of various cell types from regions proximal to these vessels to distant regions. This phenomenon is referred to as 'zonation'. Traditional analytical methods have made it difficult to investigate this zonation in detail. However, recent advancements in intravital imaging, spatial transcriptomics and single-cell transcriptomics technologies have facilitated the discovery of 'zones' in various organs and elucidated their physiological roles. Here, we outline the spatial differences in the immune system within each zone of organs. This information provides a deeper understanding of organs' immune systems.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"271-276"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141492073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rui Wang, Zhaoping Liao, Chunhua Liu, Shifang Yu, Kaihua Xiang, Ting Wu, Jie Feng, Senjuan Ding, Tingao Yu, Gang Cheng, Sanlian Li
{"title":"CRABP2 promotes cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways via upregulating LAMB3 in prostate cancer.","authors":"Rui Wang, Zhaoping Liao, Chunhua Liu, Shifang Yu, Kaihua Xiang, Ting Wu, Jie Feng, Senjuan Ding, Tingao Yu, Gang Cheng, Sanlian Li","doi":"10.1093/jb/mvae052","DOIUrl":"10.1093/jb/mvae052","url":null,"abstract":"<p><p>Prostate cancer (PCa) has become a worldwide health burden among men. Previous studies have suggested that cellular retinoic acid binding protein 2 (CRABP2) significantly affects the regulation of cell proliferation, motility and apoptosis in multiple cancers; however, the effect of CRABP2 on PCa is poorly reported. CRABP2 expression in different PCa cell lines and its effect on different cellular functions varied. While CRABP2 promotes cell migration and invasion, it appears to inhibit cell proliferation specifically in PC-3 cells. However, the proliferation of DU145 and 22RV1 cells did not appear to be significantly affected by CRABP2. Additionally, CRABP2 had no influence on the cell cycle distribution of PCa cells. The RNA-seq assay showed that overexpressing CRABP2 upregulated laminin subunit beta-3 (LAMB3) mRNA expression, and the enrichment analyses revealed that the differentially expressed genes were enriched in the phosphoinositide 3-kinase (PI3K)/activated protein kinase B (AKT) and mitogen-activated protein kinase (MAPK) signalling pathways. The following western blot experiments also confirmed the upregulated LAMB3 protein level and the activation of the PI3K/AKT and MAPK signalling pathways. Moreover, overexpressing CRABP2 significantly inhibited tumour growth in vivo. In conclusion, CRABP2 facilitates cell migration and invasion by activating PI3K/AKT and MAPK signalling pathways through upregulating LAMB3 in PCa.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"313-324"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"The Hox-based positional memory in muscle stem cells.","authors":"Ryosuke Okino, Yuki Goda, Yusuke Ono","doi":"10.1093/jb/mvae059","DOIUrl":"10.1093/jb/mvae059","url":null,"abstract":"<p><p>The skeletal muscle is a contractile tissue distributed throughout the body with various anatomical sizes, shapes and functions. In pathological conditions, such as muscular dystrophy, age-related sarcopenia and cancer cachexia, skeletal muscles are not uniformly affected throughout the body. This region-specific vulnerability cannot be fully explained by known physiological classifications, including muscle fiber types. Accumulating evidence indicates that the expression patterns of topographic homeobox (Hox) genes provide a molecular signature of positional memory, reflecting the anatomical locations and embryonic history of muscles and their associated muscle stem cells in adult mice and humans. Hox-based positional memory is not merely a remnant of embryonic development but is expected to be an intrinsic determinant controlling muscle function because recent studies have shown that aberrant Hox genes affect muscle stem cells. In this review, we discuss the concept of Hox-based positional memory, which may offer a new perspective on the region-specific pathophysiology of muscle disorders.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"277-283"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142080401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cutting-edge skin ageing research on tissue stem cell.","authors":"Ryo Ichijo","doi":"10.1093/jb/mvae022","DOIUrl":"10.1093/jb/mvae022","url":null,"abstract":"<p><p>In developed economies, the growing number of older individuals is a pressing issue. As a result, research progress into ageing has emphasized the significance of staying healthy in one's later years. Stem cells have a fundamental role to play in fostering diverse cell types and necessary processes for tissue repair and regeneration. Stem cells experience the effects of ageing over time, which is caused by their functional deterioration. Changes to stem cells, their niches and signals from other tissues they interact with are crucial factors in the ageing of stem cells. Progress in single-cell RNA sequencing (scRNA-seq) technology has greatly advanced stem cell research. This review examines the mechanisms of stem cell ageing, its impact on health and investigates the potential of stem cell therapy, with a special emphasis on the skin.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"285-288"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139972034","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Cardiac remodeling: novel pathophysiological mechanisms and therapeutic strategies.","authors":"Motohiro Nishida, Xinya Mi, Yukina Ishii, Yuri Kato, Akiyuki Nishimura","doi":"10.1093/jb/mvae031","DOIUrl":"10.1093/jb/mvae031","url":null,"abstract":"<p><p>Morphological and structural remodeling of the heart, including cardiac hypertrophy and fibrosis, has been considered as a therapeutic target for heart failure for approximately three decades. Groundbreaking heart failure medications demonstrating reverse remodeling effects have contributed significantly to medical advancements. However, nearly 50% of heart failure patients still exhibit drug resistance, posing a challenge to the healthcare system. Recently, characteristics of heart failure resistant to ARBs and β-blockers have been defined, highlighting preserved systolic function despite impaired diastolic function, leading to the classification of heart failure with preserved ejection fraction (HFpEF). The pathogenesis and aetiology of HFpEF may be related to metabolic abnormalities, as evidenced by its mimicry through endothelial dysfunction and excessive intake of high-fat diets. Our recent findings indicate a significant involvement of mitochondrial hyper-fission in the progression of heart failure. This mitochondrial pathological remodeling is associated with redox imbalance, especially hydrogen sulphide accumulation due to abnormal electron leak in myocardium. In this review, we also introduce a novel therapeutic strategy for heart failure from the current perspective of mitochondrial redox-metabolic remodeling.</p>","PeriodicalId":15234,"journal":{"name":"Journal of biochemistry","volume":" ","pages":"255-262"},"PeriodicalIF":2.1,"publicationDate":"2024-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140174872","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}