<div><h3>Introduction</h3><div>Oral squamous cell carcinomas typically arise from precancerous lesions such as leukoplakia and erythroplakia. These lesions exhibit a range of histological changes from hyperplasia to dysplasia and carcinoma in situ, during their transformation to malignancy. The molecular mechanisms driving this multistage transition remain incompletely understood. To bridge this knowledge gap, our current study utilizes label based comparative proteomics to compare protein expression profiles across different histopathological grades of leukoplakia, erythroplakia, and oral squamous cell carcinoma samples, aiming to elucidate the molecular changes underlying lesion evolution.</div></div><div><h3>Methodology</h3><div>An 8-plex iTRAQ proteomics of 4 biological replicates from 8 clinical phenotypes of leukoplakia and erythroplakia, with hyperplasia, mild dysplasia, moderate dysplasia; along with phenotypes of well differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma was carried out using the Orbitrap Fusion Lumos mass spectrometer. Raw files were processed with Maxquant, and statistical analysis across groups was conducted using MetaboAnalyst. Statistical tools such as ANOVA, PLS-DA VIP scoring, and correlation analysis were employed to identify differentially expressed proteins that had a linear expression variation across phenotypes of hyperplasia to cancer. Validation was done using Bioinformatic tools such as ClueGO + Cluepedia plugin in Cytoscape to extract functional annotations from gene ontology and pathway databases.</div></div><div><h3>Results and discussion</h3><div>A total of 2685 protein groups and 12,397 unique peptides were identified, and 61 proteins consistently exhibited valid reporter ion corrected intensities across all samples. Of these, 6 proteins showed linear varying expression across the analysed sample phenotypes. Collagen type VI alpha 2 chain (COL6A2), Fibrinogen β chain (FGB), and Vimentin (VIM) were found to have increased linear expression across pre-cancer phenotypes of leukoplakia to cancer, while Annexin A7 (ANXA7) was seen to be having a linear decreasing expression. Collagen type VI alpha 2 chain (COL6A2) and Annexin A2 (ANXA2) had increased linear expression across precancer phenotypes of erythroplakia to cancer. The mass spectrometry proteomics data have been deposited to the ProteomeXchanger Consortium via the PRIDE partner repository with the data set identifier PXD054190. These differentially expressed proteins mediate cancer progression mainly through extracellular exosome; collagen-containing extracellular matrix, hemostasis, platelet aggregation, and cell adhesion molecule binding.</div></div><div><h3>Conclusion</h3><div>Label-based proteomics is an ideal platform to study oral cancer progression. The differentially expressed proteins provide insights into the molecular mechanisms underlying the progression of oral premalignant lesions to malignant ph
{"title":"Label-based comparative proteomics of oral mucosal tissue to understand progression of precancerous lesions to oral squamous cell carcinoma","authors":"Vipra Sharma , Sundararajan Baskar Singh , Sabyasachi Bandyopadhyay , Kapil Sikka , Aanchal Kakkar , Gururao Hariprasad","doi":"10.1016/j.bbrep.2024.101842","DOIUrl":"10.1016/j.bbrep.2024.101842","url":null,"abstract":"<div><h3>Introduction</h3><div>Oral squamous cell carcinomas typically arise from precancerous lesions such as leukoplakia and erythroplakia. These lesions exhibit a range of histological changes from hyperplasia to dysplasia and carcinoma in situ, during their transformation to malignancy. The molecular mechanisms driving this multistage transition remain incompletely understood. To bridge this knowledge gap, our current study utilizes label based comparative proteomics to compare protein expression profiles across different histopathological grades of leukoplakia, erythroplakia, and oral squamous cell carcinoma samples, aiming to elucidate the molecular changes underlying lesion evolution.</div></div><div><h3>Methodology</h3><div>An 8-plex iTRAQ proteomics of 4 biological replicates from 8 clinical phenotypes of leukoplakia and erythroplakia, with hyperplasia, mild dysplasia, moderate dysplasia; along with phenotypes of well differentiated squamous cell carcinoma and moderately differentiated squamous cell carcinoma was carried out using the Orbitrap Fusion Lumos mass spectrometer. Raw files were processed with Maxquant, and statistical analysis across groups was conducted using MetaboAnalyst. Statistical tools such as ANOVA, PLS-DA VIP scoring, and correlation analysis were employed to identify differentially expressed proteins that had a linear expression variation across phenotypes of hyperplasia to cancer. Validation was done using Bioinformatic tools such as ClueGO + Cluepedia plugin in Cytoscape to extract functional annotations from gene ontology and pathway databases.</div></div><div><h3>Results and discussion</h3><div>A total of 2685 protein groups and 12,397 unique peptides were identified, and 61 proteins consistently exhibited valid reporter ion corrected intensities across all samples. Of these, 6 proteins showed linear varying expression across the analysed sample phenotypes. Collagen type VI alpha 2 chain (COL6A2), Fibrinogen β chain (FGB), and Vimentin (VIM) were found to have increased linear expression across pre-cancer phenotypes of leukoplakia to cancer, while Annexin A7 (ANXA7) was seen to be having a linear decreasing expression. Collagen type VI alpha 2 chain (COL6A2) and Annexin A2 (ANXA2) had increased linear expression across precancer phenotypes of erythroplakia to cancer. The mass spectrometry proteomics data have been deposited to the ProteomeXchanger Consortium via the PRIDE partner repository with the data set identifier PXD054190. These differentially expressed proteins mediate cancer progression mainly through extracellular exosome; collagen-containing extracellular matrix, hemostasis, platelet aggregation, and cell adhesion molecule binding.</div></div><div><h3>Conclusion</h3><div>Label-based proteomics is an ideal platform to study oral cancer progression. The differentially expressed proteins provide insights into the molecular mechanisms underlying the progression of oral premalignant lesions to malignant ph","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101842"},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433723","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Renal cell carcinoma (RCC) is a common urological cancer globally and shows a favorable prognosis in early stages of the tumor progression. Due to the poor prognosis for metastatic RCC patients, it is crucial to explore the molecular biology of RCC progression to establish efficient diagnostic and therapeutic markers for these patients. Long non-coding RNAs (lncRNAs) have critical roles in regulation of tumor cell proliferation, migration, and apoptosis during RCC progression. For the first time in the present study, we assessed the LINC01322 RNA expression levels in RCC patients to introduce that as a potential tumor marker among these patients.
Methods
we visualized LINC01322 expression data using the online tool Gene Expression Profiling Interactive Analysis (GEPIA2) across different cancers and normal tissues. Fifty fresh samples of RCC tumor tissues and their adjacent normal margins were collected to analyze the RNA expression of LINC01322 and its association with the clinicopathological features of RCC patients. The SYBR green method was used in real-time PCR to measure the LINC01322 RNA expression levels in RCC patients.
Results
Based on in-silico analysis, we hypothesized that LINC01322 could be involved in RCC progression by interacting with VHL, thereby influencing the tumor microenvironment. There were significant increased levels of LINC01322 RNA expressions in advanced stage compared with primary stage tumors that were located in left kidney (p = 0.048). Left kidney that were undergone the total nephrectomy had significant higher levels of LINC01322 RNA expressions compared with tumors in right kidney (p = 0.045). There was a direct correlation between the levels of LINC01322 RNA expression and RCC tumor size.
Conclusions
considering the substantial increase in LINC01322 RNA expression in advanced stage RCC tumors that are candidates for total nephrectomy; it could be suggested as a potential diagnostic indicator for high-risk patients. In-silico analysis also revealed that LINC01322 could be involved in regulation of tumor microenvironment during RCC progression by interacting with VHL. However, further investigations are needed to validate the potential link between LINC01322 and VHL during RCC progression. Evaluating the serum LINC01322 RNA levels in RCC patients is also necessary to use that as a diagnostic marker in clinical settings.
{"title":"LINC01322 may serve as a potential diagnostic marker for advanced stage tumors in renal cell carcinoma patients eligible for total nephrectomy","authors":"Amirhosein Maharati , Negin Taghehchian , Fatemeh Taghavinia , Alireza Golshan , Azadeh Aarabi , Mohammad Reza Abbaszadegan , Meysam Moghbeli","doi":"10.1016/j.bbrep.2024.101843","DOIUrl":"10.1016/j.bbrep.2024.101843","url":null,"abstract":"<div><h3>Background</h3><div>Renal cell carcinoma (RCC) is a common urological cancer globally and shows a favorable prognosis in early stages of the tumor progression. Due to the poor prognosis for metastatic RCC patients, it is crucial to explore the molecular biology of RCC progression to establish efficient diagnostic and therapeutic markers for these patients. Long non-coding RNAs (lncRNAs) have critical roles in regulation of tumor cell proliferation, migration, and apoptosis during RCC progression. For the first time in the present study, we assessed the LINC01322 RNA expression levels in RCC patients to introduce that as a potential tumor marker among these patients.</div></div><div><h3>Methods</h3><div>we visualized LINC01322 expression data using the online tool Gene Expression Profiling Interactive Analysis (GEPIA2) across different cancers and normal tissues. Fifty fresh samples of RCC tumor tissues and their adjacent normal margins were collected to analyze the RNA expression of LINC01322 and its association with the clinicopathological features of RCC patients. The SYBR green method was used in real-time PCR to measure the LINC01322 RNA expression levels in RCC patients.</div></div><div><h3>Results</h3><div>Based on in-silico analysis, we hypothesized that LINC01322 could be involved in RCC progression by interacting with VHL, thereby influencing the tumor microenvironment. There were significant increased levels of LINC01322 RNA expressions in advanced stage compared with primary stage tumors that were located in left kidney (p = 0.048). Left kidney that were undergone the total nephrectomy had significant higher levels of LINC01322 RNA expressions compared with tumors in right kidney (p = 0.045). There was a direct correlation between the levels of LINC01322 RNA expression and RCC tumor size.</div></div><div><h3>Conclusions</h3><div>considering the substantial increase in LINC01322 RNA expression in advanced stage RCC tumors that are candidates for total nephrectomy; it could be suggested as a potential diagnostic indicator for high-risk patients. In-silico analysis also revealed that LINC01322 could be involved in regulation of tumor microenvironment during RCC progression by interacting with VHL. However, further investigations are needed to validate the potential link between LINC01322 and VHL during RCC progression. Evaluating the serum LINC01322 RNA levels in RCC patients is also necessary to use that as a diagnostic marker in clinical settings.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101843"},"PeriodicalIF":2.3,"publicationDate":"2024-10-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142433718","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-08DOI: 10.1016/j.bbrep.2024.101837
Brenda Martins Vasconcellos , Victor Guimarães Ribeiro , Naysha do Nascimento Campos , Luis Guilherme da Silva Romão Mota , Mônica Ferreira Moreira
The enzyme arginine kinase (AK), EC 2.7.3.3, catalyzes the reversible phosphorylation of arginine with adenosine triphosphate, forming phosphoarginine, which acts as an energy reservoir due to its high-energy phosphate content that can be rapidly transferred to ADP for ATP renewal. It has been proposed that AK should be associated with some ATP biosynthesis mechanisms, such as glycolysis and oxidative phosphorylation. Arginine kinase is an analogue of creatine kinase found in vertebrates. A literature survey has recovered the physicochemical and structural characteristics of AK. This enzyme is widely distributed in invertebrates such as protozoa, bacteria, porifera, cnidaria, mollusca, and arthropods. Arginine kinase may be involved in the response to abiotic and biotic stresses, being up regulated in several organisms and controlling energy homeostasis during environmental changes. Additionally, phosphoarginine plays a role in providing energy for the transport of protozoa, the beating of cilia, and flagellar movement, processes that demand continuous energy. Arginine kinase is also associated with allergies to shellfish and arthropods, such as shrimp, oysters, and cockroaches. Phenolic compounds such as resveratrol, which decrease AK activity by 50 % in Trypanosoma cruzi, inhibit the growth of the epimastigote and trypomastigote forms, making them a significant target for the development of medications for Chagas Disease treatment.
精氨酸激酶（AK）（EC 2.7.3.3）催化精氨酸与三磷酸腺苷发生可逆磷酸化反应，形成磷精氨酸，由于磷精氨酸含有高能磷酸，可迅速转化为 ADP 用于 ATP 的更新，因此可作为能量储备。有人提出，精氨酸激酶与某些 ATP 生物合成机制有关，如糖酵解和氧化磷酸化。精氨酸激酶是脊椎动物体内肌酸激酶的类似物。一项文献调查发现了精氨酸激酶的理化和结构特征。这种酶广泛分布于无脊椎动物，如原生动物、细菌、多孔动物、刺丝胞动物、软体动物和节肢动物。精氨酸激酶可能参与了对非生物和生物压力的反应，在一些生物体内被上调，并在环境变化时控制能量平衡。此外，磷精氨酸还在为原生动物的运输、纤毛跳动和鞭毛运动等需要持续能量的过程提供能量方面发挥作用。精氨酸激酶还与对贝类和节肢动物（如虾、牡蛎和蟑螂）过敏有关。酚类化合物（如白藜芦醇）能使克氏锥虫的精氨酸激酶活性降低 50%，从而抑制表表型和试表型锥虫的生长，使其成为开发治疗南美锥虫病药物的重要目标。
{"title":"A comprehensive review of arginine kinase proteins: What we need to know?","authors":"Brenda Martins Vasconcellos , Victor Guimarães Ribeiro , Naysha do Nascimento Campos , Luis Guilherme da Silva Romão Mota , Mônica Ferreira Moreira","doi":"10.1016/j.bbrep.2024.101837","DOIUrl":"10.1016/j.bbrep.2024.101837","url":null,"abstract":"<div><div>The enzyme arginine kinase (AK), EC 2.7.3.3, catalyzes the reversible phosphorylation of arginine with adenosine triphosphate, forming phosphoarginine, which acts as an energy reservoir due to its high-energy phosphate content that can be rapidly transferred to ADP for ATP renewal. It has been proposed that AK should be associated with some ATP biosynthesis mechanisms, such as glycolysis and oxidative phosphorylation. Arginine kinase is an analogue of creatine kinase found in vertebrates. A literature survey has recovered the physicochemical and structural characteristics of AK. This enzyme is widely distributed in invertebrates such as protozoa, bacteria, porifera, cnidaria, mollusca, and arthropods. Arginine kinase may be involved in the response to abiotic and biotic stresses, being up regulated in several organisms and controlling energy homeostasis during environmental changes. Additionally, phosphoarginine plays a role in providing energy for the transport of protozoa, the beating of cilia, and flagellar movement, processes that demand continuous energy. Arginine kinase is also associated with allergies to shellfish and arthropods, such as shrimp, oysters, and cockroaches. Phenolic compounds such as resveratrol, which decrease AK activity by 50 % in <em>Trypanosoma cruzi,</em> inhibit the growth of the epimastigote and trypomastigote forms, making them a significant target for the development of medications for Chagas Disease treatment.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101837"},"PeriodicalIF":2.3,"publicationDate":"2024-10-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422980","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Globally, one of the major causes of renal dysfunction is diabetes mellitus (DM), and diabetic-induced nephrotoxicity has been linked with anemia. Presently, numerous antidiabetic drugs have been designed for the management of this disorder but they possess their undesirable effects such as anemia and acute kidney injury. Hence, we explore the use of vitamin D with or without exercise for the management of DM-induced renal dysfunction.
Methods
Thirty-six (36) Wistar rats were randomly separated into six (6) groups: control (vehicle treated), diabetes untreated (HFD + STZ), diabetes + vitamin D (HFD + STZ + vitamin D), diabetes + exercise (HFD + STZ + exercise), diabetes + vitamin D + exercise (HFD + STZ + vitamin D+ exercise), diabetes + metformin (HFD + STZ + metformin).
Results
Vitamin D with or without exercise significantly reduced T2DM-induced hyperglycemia. Also, a decrease in T2DM-induced increase in urea, creatinine, lactate dehydrogenase, lactate, cholesterol, and triglyceride and a rise in DM-associated reduction in high-density lipoprotein. These events were associated with a significant increase in red blood cells, hematocrit value, hemoglobin, erythropoietin, and a decrease in white blood cell count. Furthermore, vitamin D with or without exercise reversed T2DM-induced increase in pro-oxidant and pro-inflammatory markers. This observed oxido-inflammatory response was associated with a significant increase in xanthine oxidase activities and uric acid concentration. Interestingly, better recovery rates from DM-associated hematological imbalance were discovered in rats co-treated with vitamin D and exercise.
Conclusion
Our findings revealed that exercise enhanced the hematological effect of vitamin D in HFD + STZ-induced T2DM animals.
导言在全球范围内，导致肾功能障碍的主要原因之一是糖尿病（DM），而糖尿病引起的肾毒性与贫血有关。目前，许多抗糖尿病药物已被设计用于治疗这种疾病，但这些药物也有其不良反应，如贫血和急性肾损伤。因此，我们探讨了在运动或不运动的情况下使用维生素 D 来治疗 DM 引起的肾功能障碍。方法将 36 只 Wistar 大鼠随机分为六组：对照组（药物治疗）、未治疗糖尿病组（HFD + STZ）、糖尿病 + 维生素 D 组（HFD + STZ + 维生素 D）、糖尿病 + 运动组（HFD + STZ + 运动）、糖尿病 + 维生素 D + 运动组（HFD + STZ + 维生素 D + 运动）、糖尿病 + 二甲双胍组（HFD + STZ + 二甲双胍）。结果无论是否运动，维生素 D 都能显著降低 T2DM 引起的高血糖。此外，由 T2DM 引起的尿素、肌酐、乳酸脱氢酶、乳酸、胆固醇和甘油三酯的增加也有所减少，而由 DM 引起的高密度脂蛋白的减少则有所上升。这些事件与红细胞、血细胞比容值、血红蛋白、促红细胞生成素的显著增加和白细胞计数的减少有关。此外，无论是否运动，维生素 D 都能逆转 T2DM 诱导的促氧化和促炎症标志物的增加。观察到的这种氧化-炎症反应与黄嘌呤氧化酶活性和尿酸浓度的显著增加有关。结论我们的研究结果表明，运动增强了维生素 D 对 HFD + STZ 诱导的 T2DM 动物的血液学效应。
{"title":"Physical exercise improved the hematological effect of vitamin D in type 2 diabetes mellitus-induced nephrotoxicity in rats","authors":"Halimat Amin Abdulrahim , Adeyemi Fatai Odetayo , Adeoye Tunwagun David , Yusuf Funsho Abdulquadri , Rofiat Oluwasheun Sheu , Pelumi Kikelomo Oluwafemi , Kazeem Bidemi Okesina , Luqman Aribidesi Olayaki","doi":"10.1016/j.bbrep.2024.101839","DOIUrl":"10.1016/j.bbrep.2024.101839","url":null,"abstract":"<div><h3>Introduction</h3><div>Globally, one of the major causes of renal dysfunction is diabetes mellitus (DM), and diabetic-induced nephrotoxicity has been linked with anemia. Presently, numerous antidiabetic drugs have been designed for the management of this disorder but they possess their undesirable effects such as anemia and acute kidney injury. Hence, we explore the use of vitamin D with or without exercise for the management of DM-induced renal dysfunction.</div></div><div><h3>Methods</h3><div>Thirty-six (36) Wistar rats were randomly separated into six (6) groups: control (vehicle treated), diabetes untreated (HFD + STZ), diabetes + vitamin D (HFD + STZ + vitamin D), diabetes + exercise (HFD + STZ + exercise), diabetes + vitamin D + exercise (HFD + STZ + vitamin D+ exercise), diabetes + metformin (HFD + STZ + metformin).</div></div><div><h3>Results</h3><div>Vitamin D with or without exercise significantly reduced T2DM-induced hyperglycemia. Also, a decrease in T2DM-induced increase in urea, creatinine, lactate dehydrogenase, lactate, cholesterol, and triglyceride and a rise in DM-associated reduction in high-density lipoprotein. These events were associated with a significant increase in red blood cells, hematocrit value, hemoglobin, erythropoietin, and a decrease in white blood cell count. Furthermore, vitamin D with or without exercise reversed T2DM-induced increase in pro-oxidant and pro-inflammatory markers. This observed oxido-inflammatory response was associated with a significant increase in xanthine oxidase activities and uric acid concentration. Interestingly, better recovery rates from DM-associated hematological imbalance were discovered in rats co-treated with vitamin D and exercise.</div></div><div><h3>Conclusion</h3><div>Our findings revealed that exercise enhanced the hematological effect of vitamin D in HFD + STZ-induced T2DM animals.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101839"},"PeriodicalIF":2.3,"publicationDate":"2024-10-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142422979","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
A true native protein state is realized in a water solution where proteins exhibit their dynamic properties important for the functioning. This is way we have analyzed the dynamics of α-helices inside ribosomal protein L25 from Escherichia coli in a water solution. The dynamics of only main chain Cα-atoms have been simulated along the five independent trajectories at a total time 200ns. Superposed average dynamics picture of L25 structure coincides very well with the NMR protein structure in a water solution. Dynamic shifts of Cα-atoms of the α-helices are related with a restraint status of the residue side chain. In contrast, Cα-atoms of the β-sheet, which form a hydrophobic core, show very low dynamic motion and higher stability. Dynamic specificity of the main chain of protein L25 could explain its particular features in the complex with 5S rRNA and in the structure of the ribosome.
{"title":"Molecular dynamics of three different α-helices in ribosomal protein L25 from Escherichia coli","authors":"Yuri Chirgadze , Ilya Likhachev , Nikolai Balabaev , Evgeniy Brazhnikov","doi":"10.1016/j.bbrep.2024.101836","DOIUrl":"10.1016/j.bbrep.2024.101836","url":null,"abstract":"<div><div>A true native protein state is realized in a water solution where proteins exhibit their dynamic properties important for the functioning. This is way we have analyzed the dynamics of α-helices inside ribosomal protein L25 from <em>Escherichia coli</em> in a water solution. The dynamics of only main chain Cα-atoms have been simulated along the five independent trajectories at a total time 200ns. Superposed average dynamics picture of L25 structure coincides very well with the NMR protein structure in a water solution. Dynamic shifts of Cα-atoms of the α-helices are related with a restraint status of the residue side chain. In contrast, Cα-atoms of the β-sheet, which form a hydrophobic core, show very low dynamic motion and higher stability. Dynamic specificity of the main chain of protein L25 could explain its particular features in the complex with 5S rRNA and in the structure of the ribosome.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101836"},"PeriodicalIF":2.3,"publicationDate":"2024-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142358432","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Oxidative stress and lipid peroxide levels in the brain increase with aging. The carotenoids lutein and zeaxanthin have potent antioxidant properties and the ability to improve cognitive function. However, their effects on neuronal damage via lipid peroxidation remain unknown. Therefore, we aimed to elucidate the effects of these carotenoids on neuronal damage induced by accumulated peroxidized lipids. We developed an oxidative stress model of lipid peroxidation-induced neuronal damage using differentiated neuronal cells derived from human neuroblastoma SH-SY5Y cells in vitro. Combining rotenone and RSL3 increased mitochondrial oxidative stress and lipid reactive oxygen species (ROS), which resulted in enhanced neuronal damage. Lutein and zeaxanthin were added to the cells for 1 week, and these carotenoids suppressed mitochondrial oxidative stress and lipid peroxidation in differentiated neuronal cells and mitigated neuronal damage. Further investigation is required to clarify the underlying pathways in detail.
{"title":"Lutein and zeaxanthin reduce neuronal cell damage caused by lipid peroxidation","authors":"Satoshi Morita, Toshiaki Sueyasu, Hisanori Tokuda, Yoshihisa Kaneda, Takayuki Izumo, Yoshihiro Nakao","doi":"10.1016/j.bbrep.2024.101835","DOIUrl":"10.1016/j.bbrep.2024.101835","url":null,"abstract":"<div><div>Oxidative stress and lipid peroxide levels in the brain increase with aging. The carotenoids lutein and zeaxanthin have potent antioxidant properties and the ability to improve cognitive function. However, their effects on neuronal damage <em>via</em> lipid peroxidation remain unknown. Therefore, we aimed to elucidate the effects of these carotenoids on neuronal damage induced by accumulated peroxidized lipids. We developed an oxidative stress model of lipid peroxidation-induced neuronal damage using differentiated neuronal cells derived from human neuroblastoma SH-SY5Y cells <em>in vitro</em>. Combining rotenone and RSL3 increased mitochondrial oxidative stress and lipid reactive oxygen species (ROS), which resulted in enhanced neuronal damage. Lutein and zeaxanthin were added to the cells for 1 week, and these carotenoids suppressed mitochondrial oxidative stress and lipid peroxidation in differentiated neuronal cells and mitigated neuronal damage. Further investigation is required to clarify the underlying pathways in detail.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101835"},"PeriodicalIF":2.3,"publicationDate":"2024-09-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142327048","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.bbrep.2024.101831
Gabriela Silva , Saulo Soares da Silva , Dimitrius Santiago Passos Simões Fróes Guimarães , Marcos Vinicius da Cruz , Leonardo Reis Silveira , Etel Rocha-Vieira , Fabiano Trigueiro Amorim , Flavio de Castro Magalhaes
Obesity is a major public health problem and is a major contributor to the development of insulin resistance. In previous studies we observed that single-wavelength red or infrared photobiomodulation (PBM) improved insulin signaling in adipocytes and skeletal muscle of mice fed a high-fat diet, but information about the combination of different wavelengths, as well as the effect of different light doses (J/cm2) is lacking. Therefore, the aim of this study was to investigate the effects of different doses of dual-wavelength PBM on insulin signaling in muscle cell, and explore potential mechanisms involved. Mouse myoblasts (C2C12) were differentiated into myotubes and cultured in palmitic acid, sodium oleate and l-carnitine (PAL) to induce insulin resistance high or in glucose medium (CTRL). Then, they received SHAM treatment (lights off, 0 J/cm2) or PBM (660 + 850 nm; 2, 4 or 8 J/cm2). PAL induced insulin resistance (assessed by Akt phosphorylation at ser473), attenuated maximal citrate synthase activity, and increased the phosphorylation of c-Jun NH(2) terminal kinase (JNK) (T183/Y185). PBM at doses of 4 or 8 J/cm2 reversed these PAL-induced responses. Furthermore, at doses of 2, 4 or 8 J/cm2, PBM reversed the increase in mitofusin-2 content induced by PAL. In conclusion, the combination of dual-wavelength red and infrared PBM at doses of 4 and 8 J/cm2 improved intracellular insulin signaling in musculoskeletal cells, and this effect appears to involve the modulation of mitochondrial function and the attenuation of the activation of stress kinases.
{"title":"The dose-effect response of combined red and infrared photobiomodulation on insulin resistance in skeletal muscle cells","authors":"Gabriela Silva , Saulo Soares da Silva , Dimitrius Santiago Passos Simões Fróes Guimarães , Marcos Vinicius da Cruz , Leonardo Reis Silveira , Etel Rocha-Vieira , Fabiano Trigueiro Amorim , Flavio de Castro Magalhaes","doi":"10.1016/j.bbrep.2024.101831","DOIUrl":"10.1016/j.bbrep.2024.101831","url":null,"abstract":"<div><div>Obesity is a major public health problem and is a major contributor to the development of insulin resistance. In previous studies we observed that single-wavelength red or infrared photobiomodulation (PBM) improved insulin signaling in adipocytes and skeletal muscle of mice fed a high-fat diet, but information about the combination of different wavelengths, as well as the effect of different light doses (J/cm<sup>2</sup>) is lacking. Therefore, the aim of this study was to investigate the effects of different doses of dual-wavelength PBM on insulin signaling in muscle cell, and explore potential mechanisms involved. Mouse myoblasts (C2C12) were differentiated into myotubes and cultured in palmitic acid, sodium oleate and <span>l</span>-carnitine (PAL) to induce insulin resistance high or in glucose medium (CTRL). Then, they received SHAM treatment (lights off, 0 J/cm<sup>2</sup>) or PBM (660 + 850 nm; 2, 4 or 8 J/cm<sup>2</sup>). PAL induced insulin resistance (assessed by Akt phosphorylation at ser473), attenuated maximal citrate synthase activity, and increased the phosphorylation of c-Jun NH(2) terminal kinase (JNK) (T183/Y185). PBM at doses of 4 or 8 J/cm<sup>2</sup> reversed these PAL-induced responses. Furthermore, at doses of 2, 4 or 8 J/cm<sup>2</sup>, PBM reversed the increase in mitofusin-2 content induced by PAL. In conclusion, the combination of dual-wavelength red and infrared PBM at doses of 4 and 8 J/cm<sup>2</sup> improved intracellular insulin signaling in musculoskeletal cells, and this effect appears to involve the modulation of mitochondrial function and the attenuation of the activation of stress kinases.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101831"},"PeriodicalIF":2.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322969","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-26DOI: 10.1016/j.bbrep.2024.101833
Jie Yu , Wenke Cai , Tao Zhou , Bo Men , Shunqiong Chen , Dong Tu , Wei Guo , Jicui Wang , Feipeng Zhao , Yan Wang
Background
Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC.
Methods
A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF–κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay.
Results
CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF–κB pathway and, therefore, promote lymphangiogenesis.
Conclusion
We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.
{"title":"CEACAM1 increased the lymphangiogenesis through miR-423-5p and NF- kB in Non-Small Cell Lung Cancer","authors":"Jie Yu , Wenke Cai , Tao Zhou , Bo Men , Shunqiong Chen , Dong Tu , Wei Guo , Jicui Wang , Feipeng Zhao , Yan Wang","doi":"10.1016/j.bbrep.2024.101833","DOIUrl":"10.1016/j.bbrep.2024.101833","url":null,"abstract":"<div><h3>Background</h3><div>Lung cancer causes significant mortality, with invasion and metastasis being the main features that cause most cancer deaths. Lymph node metastasis is the primary metastatic route in non-small cell carcinoma (NSCLC) and influences the staging and prognosis of NSCLC. Cumulative studies have reported that Carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) is involved in the progression of various cancers. However, few studies have discussed the function of CEACAM1 in lymphangiogenesis in NSCLC. Here, we examined how CEACAM1 influences lymphangiogenesis in NSCLC.</div></div><div><h3>Methods</h3><div>A total of 30 primary squamous cell carcinoma (LUSC) patients diagnosed with LN metastasis were prospectively selected. LUSC tumor tissues, para-cancerous tissues, and positive lymph node tissues were harvested. The expression and subcellular location of CEACAM1, CD31, and LVYE1 in clinical samples were detected by immunohistochemistry. Next, the CEACAM1 and hsa-miR-423-5p expressions were detected by qPCR. The protein expression of lymphangiogenesis-associated proteins and critical cytokines of the NF–κB pathway in HDLECs was detected by Western blot. A tube formation assay was performed to detect the lymphangiogenesis in different groups. The interaction between CEACAM1 and hsa-miR-423-5p was verified using a dual luciferase assay.</div></div><div><h3>Results</h3><div>CEACAM1 was found to be a potential gene associated with lung cancer prognosis. It was positively correlated with angiogenesis and lymphangiogenesis. Then, we detected the function of CEACAM1 in lymphangiogenesis and found that CEACAM1 promoted lymphangiogenesis. hsa-miR-423-5p overexpression inhibited lymphangiogenesis via targeting CEACAM1. Finally, we observed that CEACAM1 can activate the NF–κB pathway and, therefore, promote lymphangiogenesis.</div></div><div><h3>Conclusion</h3><div>We found that CEACAM1 enhanced lymphangiogenesis in NSCLC via NF-kB activation and was repressed by miR-423-5p. This suggests the value of CEACAM1 as a new therapeutic marker in NSCLC.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101833"},"PeriodicalIF":2.3,"publicationDate":"2024-09-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142322893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-09-25DOI: 10.1016/j.bbrep.2024.101828
Erik Wåhlén, Johan Lennartsson , Johan Heldin
This study investigates the role of Rho GTPases, specifically Cdc42, Rac1, and RhoA, in platelet-derived growth factor receptors (PDGFRα and PDGFRβ) signaling. Signal transducer and activator of transcription (STAT) proteins, essential for cellular processes such as proliferation and immune response, are activated downstream of PDGFRs. Dysregulation of these pathways is linked to various diseases, including cancer. The current study examines the effects of Rho GTPase depletion on PDGFR phosphorylation, STAT protein stability, and downstream signaling. Results indicate that depletion of Cdc42, Rac1, or RhoA impairs PDGFR phosphorylation and reduces STAT1 and STAT3 signaling, without significantly affecting AKT and ERK1/2 pathways. The findings highlight the critical regulatory roles of Rho GTPases in PDGFR-mediated STAT signaling.
{"title":"Depletion of the Rho GTPases Cdc42, Rac1 or RhoA reduces PDGF-induced STAT1 and STAT3 signaling","authors":"Erik Wåhlén, Johan Lennartsson , Johan Heldin","doi":"10.1016/j.bbrep.2024.101828","DOIUrl":"10.1016/j.bbrep.2024.101828","url":null,"abstract":"<div><div>This study investigates the role of Rho GTPases, specifically Cdc42, Rac1, and RhoA, in platelet-derived growth factor receptors (PDGFRα and PDGFRβ) signaling. Signal transducer and activator of transcription (STAT) proteins, essential for cellular processes such as proliferation and immune response, are activated downstream of PDGFRs. Dysregulation of these pathways is linked to various diseases, including cancer. The current study examines the effects of Rho GTPase depletion on PDGFR phosphorylation, STAT protein stability, and downstream signaling. Results indicate that depletion of Cdc42, Rac1, or RhoA impairs PDGFR phosphorylation and reduces STAT1 and STAT3 signaling, without significantly affecting AKT and ERK1/2 pathways. The findings highlight the critical regulatory roles of Rho GTPases in PDGFR-mediated STAT signaling.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101828"},"PeriodicalIF":2.3,"publicationDate":"2024-09-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142318585","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Recently, targeted protein degradation has attracted increasing interest as a new drug discovery approach. This method aims to control the function of drug targets by inducing their degradation through protein degradation systems such as the proteasome. Concurrently, compounds that enhance proteasome activity have also garnered attention. In 2023, we reported that anthricin (also known as 4-deoxypodophyllotoxin), a natural product that belongs to the lignan family, enhances proteasome activity. However, whether this enhancement was because of increased proteasome expression or improved proteasome function remains unclear. In this study, we investigated the structure–activity relationship of anthricin and its analogs in enhancing proteasome activity, the effects of anthricin on proteasome-related gene expression, and the direct binding between anthricin and the proteasome using pull-down assay. Moreover, we assessed the interaction between anthricin and the proteasome using molecular dynamics (MD) simulations. The results showed that anthricin does not induce proteasome-related gene expression, but instead binds to the β-subunit of the proteasome, bringing the side chains of three amino acid residues (Thr1, Asp17, and Lys33) at the catalytic site closer together, thereby inducing a hyperactive state. To the best of our knowledge, this study is the first to suggest the mechanism of proteasome activity enhancement by anthricin at the molecular level. The findings could contribute to the development of new chemotypes to enhance the effects of targeted protein degraders by regulating proteasome activity.
{"title":"Anthricin-induced hyperactive proteasome and its molecular mechanism","authors":"Kotaro Sakamoto , Runa Fujimoto , Erina Kamiyama-Ando , Takatsugu Hirokawa","doi":"10.1016/j.bbrep.2024.101830","DOIUrl":"10.1016/j.bbrep.2024.101830","url":null,"abstract":"<div><div>Recently, targeted protein degradation has attracted increasing interest as a new drug discovery approach. This method aims to control the function of drug targets by inducing their degradation through protein degradation systems such as the proteasome. Concurrently, compounds that enhance proteasome activity have also garnered attention. In 2023, we reported that anthricin (also known as 4-deoxypodophyllotoxin), a natural product that belongs to the lignan family, enhances proteasome activity. However, whether this enhancement was because of increased proteasome expression or improved proteasome function remains unclear. In this study, we investigated the structure–activity relationship of anthricin and its analogs in enhancing proteasome activity, the effects of anthricin on proteasome-related gene expression, and the direct binding between anthricin and the proteasome using pull-down assay. Moreover, we assessed the interaction between anthricin and the proteasome using molecular dynamics (MD) simulations. The results showed that anthricin does not induce proteasome-related gene expression, but instead binds to the β-subunit of the proteasome, bringing the side chains of three amino acid residues (Thr<sup>1</sup>, Asp<sup>17</sup>, and Lys<sup>33</sup>) at the catalytic site closer together, thereby inducing a hyperactive state. To the best of our knowledge, this study is the first to suggest the mechanism of proteasome activity enhancement by anthricin at the molecular level. The findings could contribute to the development of new chemotypes to enhance the effects of targeted protein degraders by regulating proteasome activity.</div></div>","PeriodicalId":8771,"journal":{"name":"Biochemistry and Biophysics Reports","volume":"40 ","pages":"Article 101830"},"PeriodicalIF":2.3,"publicationDate":"2024-09-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2405580824001948/pdfft?md5=343c70f733b5a3b299d119af0b30f2b1&pid=1-s2.0-S2405580824001948-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142311014","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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