Biological Chemistry最新文献

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-25 DOI: 10.1515/hsz-2024-0146

Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen

{"title":"How neurons cope with oxidative stress.","authors":"Johannes Ebding, Fiorella Mazzone, Stefan Kins, Jan Pielage, Tanja Maritzen","doi":"10.1515/hsz-2024-0146","DOIUrl":"https://doi.org/10.1515/hsz-2024-0146","url":null,"abstract":"Neurons are highly dependent on mitochondrial respiration for energy, rendering them vulnerable to oxidative stress. Reactive oxygen species (ROS), by-products of oxidative phosphorylation, can damage lipids, proteins, and DNA, potentially triggering cell death pathways. This review explores the neuronal vulnerability to ROS, highlighting metabolic adaptations and antioxidant systems that mitigate oxidative damage. Balancing metabolic needs and oxidative stress defenses is critical for neurons, as disruptions are implicated in neurodegenerative diseases. Neurons uniquely modulate metabolic pathways, favoring glycolysis over oxidative phosphorylation in cell bodies, to minimize harmful ROS production. Key antioxidants, including superoxide dismutases and glutathione peroxidases, play crucial roles in neuronal protection, as evident from genetic studies linking deficiencies to neurodegeneration. Notably, neurons have the ability to adapt to oxidative conditions in compartment-specific manners and also utilize ROS as a signaling molecule to promote adaptive synaptic plasticity. Future research should aim to elucidate differential ROS signaling and antioxidant responses across neuronal compartments for improved therapeutic strategies.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143482006","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}

引用次数: 0

Protein kinase CK2 contributes to glucose homeostasis.

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-02-07 DOI: 10.1515/hsz-2024-0158

Claudia Götz, Mathias Montenarh

{"title":"Protein kinase CK2 contributes to glucose homeostasis.","authors":"Claudia Götz, Mathias Montenarh","doi":"10.1515/hsz-2024-0158","DOIUrl":"https://doi.org/10.1515/hsz-2024-0158","url":null,"abstract":"In the early days of CK2 research, it was already published that the affinity of CK2 for its substrate casein was affected by insulin. Subsequent to the discovery of inhibitors of CK2 kinase activity, it was shown that CK2 has an influence on hormones that regulate glucose homeostasis and on enzymes that influence glucose metabolism in pancreatic islet cells as well as in hormone-sensitive target cells. This regulation includes the influence on transcription factors and thereby, gene expression, as well as direct modulation of the catalytic activity. The used CK2 inhibitors, especially the older ones, show a broad range of specificity, selectivity and off-target effects. Recently applied methods to down-regulate the expression of individual CK2 subunits using siRNA or CRISPR/Cas9 technology have contributed to the improvement of specificity. It was shown that inhibition of CK2 kinase activity or knock-down or knock-out of CK2α leads to an elevated synthesis and secretion of insulin in pancreatic β-cells and a down-regulation of the synthesis and secretion of glucagon from pancreatic α-cells. In the present review CK2-dependent molecular mechanisms will be addressed which contribute to the maintenance of glucose homeostasis.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143254548","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}

引用次数: 0

MitoStores: stress-induced aggregation of mitochondrial proteins. 线粒体：应激诱导的线粒体蛋白聚集。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-01-21 DOI: 10.1515/hsz-2024-0148

Pragya Kaushik, Johannes M Herrmann, Katja G Hansen

{"title":"MitoStores: stress-induced aggregation of mitochondrial proteins.","authors":"Pragya Kaushik, Johannes M Herrmann, Katja G Hansen","doi":"10.1515/hsz-2024-0148","DOIUrl":"https://doi.org/10.1515/hsz-2024-0148","url":null,"abstract":"Most mitochondrial proteins are synthesized in the cytosol and post-translationally imported into mitochondria. If the rate of protein synthesis exceeds the capacity of the mitochondrial import machinery, precursor proteins can transiently accumulate in the cytosol. The cytosolic accumulation of mitochondrial precursors jeopardizes cellular protein homeostasis (proteostasis) and can be the cause of diseases. In order to prevent these toxic effects, most non-imported precursors are rapidly degraded by the ubiquitin-proteasome system. However, cells employ a second layer of defense which is the facilitated sequestration of mitochondrial precursor proteins in transient protein aggregates. The formation of such structures is triggered by nucleation factors such as small heat shock proteins. Disaggregases and chaperones can liberate precursors from cytosolic aggregates to pass them on to the mitochondrial import machinery or, under persistent stress conditions, to the proteasome for degradation. Owing to their role as transient buffering systems, these aggregates were referred to as MitoStores. This review articles provides a general overview about the MitoStore concept and the early stages in mitochondrial protein biogenesis in yeast and, in cases where aspects differ, in mammalian cells.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2025-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999503","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}

引用次数: 0

Revival of the Escherichia coli heat shock response after two decades with a small Hsp in a critical but distinct act. 大肠杆菌热休克反应在小热休克二十年后的复苏是一个关键但独特的行为。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2025-01-07 DOI: 10.1515/hsz-2024-0140

Tsukumi Miwa, Hideki Taguchi

引用次数: 0

Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking. 羟基查尔酮在体外缺血-再氧化模型中的生物探测及NOX4分子对接的相互作用。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-23 Print Date: 2024-12-17 DOI: 10.1515/hsz-2024-0068

Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins

{"title":"Bioprospecting hydroxylated chalcones in in vitro model of ischemia-reoxygenation and probing NOX4 interactions via molecular docking.","authors":"Arif Ali, Igor Moreira de Almeida, Emanuel Paula Magalhães, Jesyka Macedo Guedes, Francisco Ferdinando Mesquita Cajazeiras, Marcia Machado Marinho, Emmanuel Silva Marinho, Ramon Róseo Paula Pessoa Bezerra de Menezes, Tiago Lima Sampaio, Hélcio Silva Dos Santos, Geraldo Bezerra da Silva Júnior, Alice Maria Costa Martins","doi":"10.1515/hsz-2024-0068","DOIUrl":"10.1515/hsz-2024-0068","url":null,"abstract":"Ischemia/reperfusion injury (I/R) is a leading cause of acute kidney injury (AKI) in conditions like kidney transplants, cardiac surgeries, and nephrectomy, contributing to high global mortality and morbidity. This study aimed to analyze the protective effects of 2'-hydroxychalcones in treating I/R-induced AKI by targeting key pathological pathways. Considering strong antioxidant action along with other pharmacological roles of chalcone derivatives, six 2'-hydroxychalcones were synthesized via Claisen-Schmidt condensation and analyzed for their protective effects in an I/R induced AKI model using HK-2 cells. Among six 2'-hydroxychalcones, chalcone A4 significantly increased the HK-2 cells viability compared to I/R group. Chalcone A4 reduced the cell death events by reducing generation of cytoplasmic ROS and mitochondrial transmembrane potential. It also increased GSH and SOD activity while reducing TBARS levels, indicating strong antioxidant action. Scanning electron microscope images showed that chalcone A4 reversed I/R-induced morphological changes in HK-2 cells, including apoptotic blebbing and cytoplasmic fragmentation. Furthermore, in silico studies revealed interactions with NADPH oxidase 4, further supporting its protective role in I/R-induced AKI. These results showed that chalcone A4 possess potential protective action against I/R induced cellular damage possibly due to its strong antioxidant action and potential interaction with NOX4 subunit of NADPH oxidase.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"727-743"},"PeriodicalIF":2.9,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142869351","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}

引用次数: 0

Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates. 分析钾化钾素相关肽酶7 （KLK7）自溶揭示了新的蛋白酶和细胞因子底物。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-11 DOI: 10.1515/hsz-2024-0127

Swapnil V Ghodge, Robert A Lazarus

{"title":"Analysis of kallikrein-related peptidase 7 (KLK7) autolysis reveals novel protease and cytokine substrates.","authors":"Swapnil V Ghodge, Robert A Lazarus","doi":"10.1515/hsz-2024-0127","DOIUrl":"https://doi.org/10.1515/hsz-2024-0127","url":null,"abstract":"Kallikrein-related peptidase 7 (KLK7) is one of 15 members of the tissue kallikrein family and is primarily expressed in the skin epidermis. The activity of KLK7 is tightly regulated by multiple stages of maturation and reversible inhibition, similar to several other extracellular proteases. In this work, we used protease-specific inhibitors and active site variants to show that KLK7 undergoes autolysis at two separate sites in the 170 and 99 loops (chymotrypsinogen numbering), resulting in a loss of enzymatic activity. A protein BLAST search using the autolyzed KLK7 loop sequences identified mast cell chymase as a potential KLK7 substrate. Indeed, KLK7 cleaves chymase resulting in a concomitant loss of activity. We further demonstrate that KLK7 can hydrolyze other mast cell proteases as well as several cytokines. These cytokines belong mainly to the interferon and IL-10 families including IFN-α, IFN-β, IFN-γ, IL-28A/IFN-λ2, IL-20, IL-22, and IL-27. This is the first study to identify a possible molecular interaction link between KLK7 and mast cell proteases and cytokines. Although the precise biological implications of these findings are unclear, this study extends our understanding of the delicate balance of proteolytic regulation of enzyme activity that maintains physiological homeostasis, and facilitates further biological investigations.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":""},"PeriodicalIF":2.9,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142799479","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}

引用次数: 0

Carnosic acid prevents heat stress-induced oxidative damage by regulating heat-shock proteins and apoptotic proteins in mouse testis. 鼠尾草酸通过调节小鼠睾丸热休克蛋白和凋亡蛋白来预防热应激诱导的氧化损伤。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-12-06 Print Date: 2024-12-17 DOI: 10.1515/hsz-2023-0374

Sirui Liu, Jiaxin Wu, Wanqing Liang, Yinkun Liu, Shuangshuang Wan, Shu Tang

引用次数: 0

Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein. 锌和铜对淀粉样前体蛋白机械细胞粘附特性的影响

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-21 Print Date: 2024-12-17 DOI: 10.1515/hsz-2024-0054

Alexander August, Sabrina Hartmann, Sandra Schilling, Christine Müller-Renno, Tarik Begic, Antonio J Pierik, Christiane Ziegler, Stefan Kins

{"title":"Zinc and copper effect mechanical cell adhesion properties of the amyloid precursor protein.","authors":"Alexander August, Sabrina Hartmann, Sandra Schilling, Christine Müller-Renno, Tarik Begic, Antonio J Pierik, Christiane Ziegler, Stefan Kins","doi":"10.1515/hsz-2024-0054","DOIUrl":"10.1515/hsz-2024-0054","url":null,"abstract":"The amyloid precursor protein (APP) can be modulated by the binding of copper and zinc ions. Both ions bind with low nanomolar affinities to both subdomains (E1 and E2) in the extracellular domain of APP. However, the impact of ion binding on structural and mechanical trans-dimerization properties is yet unclear. Using a bead aggregation assay (BAA), we found that zinc ions increase the dimerization of both subdomains, while copper promotes only dimerization of the E1 domain. In line with this, scanning force spectroscopy (SFS) analysis revealed an increase in APP adhesion force up to three-fold for copper and zinc. Interestingly, however, copper did not alter the separation length of APP dimers, whereas high zinc concentrations caused alterations in the structural features and a decrease of separation length. Together, our data provide clear differences in copper and zinc mediated APP trans-dimerization and indicate that zinc binding might favor a less flexible APP structure. This fact is of significant interest since changes in zinc and copper ion homeostasis are observed in Alzheimer's disease (AD) and were reported to affect synaptic plasticity. Thus, modulation of APP trans-dimerization by copper and zinc could contribute to early synaptic instability in AD.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"701-710"},"PeriodicalIF":2.9,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457112","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}

引用次数: 0

A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries. 从酵母表面展示库中早期筛选非竞争性抗体片段的平台。

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-01 Print Date: 2024-12-17 DOI: 10.1515/hsz-2024-0102

Léxane Fournier, Deniz Demir, Desislava Elter, Lukas Pekar, Harald Kolmar, Lars Toleikis, Stefan Becker

{"title":"A platform for the early selection of non-competitive antibody-fragments from yeast surface display libraries.","authors":"Léxane Fournier, Deniz Demir, Desislava Elter, Lukas Pekar, Harald Kolmar, Lars Toleikis, Stefan Becker","doi":"10.1515/hsz-2024-0102","DOIUrl":"10.1515/hsz-2024-0102","url":null,"abstract":"In this work, we report the development of a platform for the early selection of non-competitive antibody-fragments against cell surface receptors that do not compete for binding of their natural ligand. For the isolation of such subtype of blocking antibody-fragments, we applied special fluorescence-activated cell sorting strategies for antibody fragments isolation from yeast surface display libraries. Given that most of the monoclonal antibodies approved on the market are blocking ligand-receptor interactions often leading to resistance and/or side effects, targeting allosteric sites represents a promising mechanism of action to open new avenues for treatment. To directly identify these antibody-fragments during library screening, we employed immune libraries targeting the epidermal growth factor receptor as proof of concept. Incorporating a labeled orthosteric ligand during library sorting enables the early selection of non-competitive binders and introduces an additional criterion to refine the selection of candidates exhibiting noteworthy properties. Furthermore, after sequencing, more candidates were identified compared to classical sorting based solely on target binding. Hence, this platform can significantly improve the drug discovery process by the early selection of more candidates with desired properties.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":" ","pages":"765-775"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142340553","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}

引用次数: 0

Implications of TRPM3 and TRPM8 for sensory neuron sensitisation. TRPM3 和 TRPM8 对感觉神经元敏化的影响

IF 2.9 4区生物学

Biological Chemistry Pub Date : 2024-10-01 Print Date: 2024-10-28 DOI: 10.1515/hsz-2024-0045

Marc Behrendt

{"title":"Implications of TRPM3 and TRPM8 for sensory neuron sensitisation.","authors":"Marc Behrendt","doi":"10.1515/hsz-2024-0045","DOIUrl":"10.1515/hsz-2024-0045","url":null,"abstract":"Sensory neurons serve to receive and transmit a wide range of information about the conditions of the world around us as well as the external and internal state of our body. Sensitisation of these nerve cells, i.e. becoming more sensitive to stimuli or the emergence or intensification of spontaneous activity, for example in the context of inflammation or nerve injury, can lead to chronic diseases such as neuropathic pain. For many of these disorders there are only very limited treatment options and in order to find and establish new therapeutic approaches, research into the exact causes of sensitisation with the elucidation of the underlying mechanisms and the identification of the molecular components is therefore essential. These components include plasma membrane receptors and ion channels that are involved in signal reception and transmission. Members of the transient receptor potential (TRP) channel family are also expressed in sensory neurons and some of them play a crucial role in temperature perception. This review article focuses on the heat-sensitive TRPM3 and the cold-sensitive TRPM8 (and TRPA1) channels and their importance in sensitisation of dorsal root ganglion sensory neurons is discussed based on studies related to inflammation and injury- as well as chemotherapy-induced neuropathy.","PeriodicalId":8885,"journal":{"name":"Biological Chemistry","volume":"405 9-10","pages":"583-599"},"PeriodicalIF":2.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142457113","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}

引用次数: 0