International Journal of Biochemistry & Cell Biology最新文献

{"title":"Association of long non-coding RNA in lipid metabolism: Implications in leukemia","authors":"Anjani Alluri ,&nbsp;Pallavi Saxena ,&nbsp;Amit Mishra ,&nbsp;Ravi Kumar Gutti","doi":"10.1016/j.biocel.2025.106785","DOIUrl":"10.1016/j.biocel.2025.106785","url":null,"abstract":"<div><div>Cancer has high mortality rate and occupies second position among major diseases. Despite extensive research and therapies, in every nook and corner of the world, death rate is increasing exponentially. Hallmarks of cancer are benchmarks of cancer cells describing the fundamental principle and capabilities of the cells transforming from normal to malignant tumour. One of the major ones among them is the deregulation of cellular metabolism or metabolic reprogramming, involving alterations in glucose and lipid metabolism. Progressive research in this area has visualized the vital role of lncRNAs in lipid metabolism with respect to AML. lncRNAs involve in various cellular processes and also contribute for significant functions of the cell like chromatin remodelling, transcriptional activation and repression, gene regulation, immune response, cell differentiation, and cell cycle regulation, in addition to oncogenic processes such as proliferation, angiogenesis, migration, and apoptosis. Structural similarities are observed among mRNAs and lncRNAs in terms of poly A-tail and 5^’ cap however protein-coding regions are lacking. A large body of evidence has shown that lncRNAs directly or indirectly mediate lipid metabolism by activating downstream genes. Considering their potential involvement in leukemia, these lncRNAs can be explored and considered as biomarkers for therapeutics, prognosis, and diagnosis. The present review is planned to summarize the functional classification of lncRNAs, the role of lipid metabolism in cancer, different lncRNAs involved in leukemia, and different cancer types related to lipid metabolism.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106785"},"PeriodicalIF":3.4,"publicationDate":"2025-04-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Multi-channel smFRET study reveals a compact conformation of EF-G on the ribosome","authors":"Jordan L. Johnson ,&nbsp;Jacob H. Steele ,&nbsp;Ran Lin ,&nbsp;Victor G. Stepanov,&nbsp;Miriam N. Gavriliuc ,&nbsp;Yuhong Wang","doi":"10.1016/j.biocel.2025.106782","DOIUrl":"10.1016/j.biocel.2025.106782","url":null,"abstract":"<div><div>While elongation factor G (EF-G) is crucial for ribosome translocation, the role of its GTP hydrolysis remains ambiguous. EF-G's indispensability is further exemplified by the phosphorylation of human eukaryotic elongation factor 2 (eEF2) at Thr56, which inhibits protein synthesis globally, but its exact mechanism is not clear. In this study, we developed a multi-channel single-molecule FRET (smFRET) microscopy methodology to examine the conformational changes of <em>E. coli</em> EF-G induced by mutations that closely aligned with eEF2's Thr56 residue. We utilized Alexa 488/594 double-labeled EF-G to catalyze the translocation of fMet-Phe-tRNA^Phe-Cy3 inside Cy5-L27 labeled ribosomes, allowing us to probe both processes within the same complex. Our findings indicate that in the presence of either GTP or GDPCP, wild-type EF-G undergoes a conformational extension upon binding to the ribosome to promote normal translocation. On the other hand, the T48E and T48V mutations did not affect GTP/GDP binding or GTP hydrolysis, but impeded Poly(Phe) synthesis and caused EF-G to adopt a unique compact conformation, which was not observed when the mutants interact solely with the SRL. This study provides new insights into EF-G's adaptability and sheds light on the modification mechanism of human eEF2.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106782"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hematopoietic stem cell conditioned media induces apoptosis in colorectal cancer stem cells via dysregulation of HSP90 and 26S proteasome system","authors":"Sumit Mallick ,&nbsp;Vanya Kadla Narayana ,&nbsp;Akhila Balakrishna Rai ,&nbsp;Shubham Sukerndeo Upadhyay ,&nbsp;Thottethodi Subrahmanya Keshava Prasad ,&nbsp;Sudheer Shenoy P ,&nbsp;Bipasha Bose (Lead contact)","doi":"10.1016/j.biocel.2025.106773","DOIUrl":"10.1016/j.biocel.2025.106773","url":null,"abstract":"<div><div>Cancer stem cells (CSCs) hold a significant role in cancer metastasis, high mortality and severity responsible for therapy resistance and tumour recurrence. The 26S proteasome system plays a major role in protein degradation in normal cells. As most cancers have upregulated 26S proteasome machinery, cancer cells use the 26S proteasome system in their favour for growth support by degrading unwanted proteins, but dysfunction of the 26S proteasome system induces apoptosis in cells. Here, we used hematopoietic stem cells (HSCs) and HSCs-derived conditioned media (CM) to target colorectal cancer stem cells (CRC-CSCs). HSCs are otherwise used extensively to save the lives of patients suffering from hematological malignancies and inherited blood disorders. HSCs-derived conditioned media contains various cytokines, chemokines, and secretory small molecules, which can also target the CRC-CSCs. Moreover, HSCs have exhibited CRC-CSC tropism in vitro in our pilot studies. As therapeutic uses of HSCs for targeting colorectal cancer (CRC) have never been reported, we hypothesized the CRC-CSC targeting properties of HSCs. Our results indicated altered protein function of CRC-CSCs upon co-culture with HSCs. Proteomics approaches showed that HSCs-CM disrupted 26S proteasomal complex and altered the mitochondrial bioenergetics, thereby activating apoptosis in CRC-CSCs. Furthermore, we observed that HSCs-CM significantly induced double-stranded DNA damage and proteasomal degradation, leading to apoptosis and upregulating the autophagy system. This study, hence, provides the prospective targeting of cancer stem cells using HSCs-CM, indicating a possible therapeutic approach.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"184 ","pages":"Article 106773"},"PeriodicalIF":3.4,"publicationDate":"2025-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143842684","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mitochondrial and peroxisomal fission in cortical neurogenesis","authors":"Gabriella L. Robertson ,&nbsp;Caroline Bodnya ,&nbsp;Vivian Gama","doi":"10.1016/j.biocel.2025.106774","DOIUrl":"10.1016/j.biocel.2025.106774","url":null,"abstract":"<div><div>The human brain is unique in its cellular diversity, intricate cytoarchitecture, function, and complex metabolic and bioenergetic demands, for which mitochondria and peroxisomes are essential. Mitochondria are multifunctional organelles that coordinate various signaling pathways central to neurogenesis. The dynamic morphological changes of the mitochondrial network have been linked to the regulation of bioenergetic and metabolic states. Specific protein machinery is dedicated to mitochondrial fission and fusion, allowing organelle distribution during cell division, organelle repair, and adaptation to environmental stimuli (excellent reviews have been published on these topics [<span><span>Kondadi and Reichert, 2024</span></span>; <span><span>Giacomello et al., 2020</span></span>; <span><span>Tilokani et al., 2018</span></span>; <span><span>Kraus et al., 2021</span></span>; <span><span>Navaratnarajah et al., 2021</span></span>]). In parallel, peroxisomes contain over 50 different enzymes which regulate metabolic functions that are critical for neurogenesis (<span><span>Berger et al., 2016</span></span>, <span><span>Hulshagen et al., 2008</span></span>). Peroxisomes share many of the components of their fission machinery with the mitochondria and undergo fission to help meet metabolic demands in response to environmental stimuli (<span><span>Schrader et al., 2016</span></span>). This review focuses primarily on the machinery involved in mitochondrial and peroxisomal fission. Mitochondrial fission has been identified as a critical determinant of cell fate decisions (<span><span>Iwata et al., 2023</span></span>, <span><span>Iwata et al., 2020</span></span>, <span><span>Khacho et al., 2016</span></span>, <span><span>King et al., 2021</span></span>, <span><span>Prigione and Adjaye, 2010</span></span>, <span><span>Vantaggiato et al., 2019</span></span>, <span><span>Kraus et al., 2021</span></span>). The connection between alterations in peroxisomal fission and metabolic changes associated with cellular differentiation remains less clear. Here, we provide an overview of the functional and regulatory aspects of the mitochondrial and peroxisomal fission machinery and provide insight into the current mechanistic understanding by which mitochondrial and peroxisomal fission influence neurogenesis.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"182 ","pages":"Article 106774"},"PeriodicalIF":3.4,"publicationDate":"2025-03-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143755855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Selective cerebral hypothermia alleviates focal cerebral ischemia/reperfusion injury via enhancing SUMO2/3 modification of Drp1 in rats","authors":"Yang Yuan ,&nbsp;Li Fu ,&nbsp;Wenji Liu ,&nbsp;Rui Dong ,&nbsp;Fei Shi ,&nbsp;Jinhao Liu ,&nbsp;Hong Li ,&nbsp;Gaofeng Zhang","doi":"10.1016/j.biocel.2025.106772","DOIUrl":"10.1016/j.biocel.2025.106772","url":null,"abstract":"<div><h3>Background</h3><div>Selective Cerebral Hypothermia (SCH) has been demonstrated to potentiate SUMO2/3 modification, a native cellular safeguard against Cerebral Ischemia/Reperfusion Injury (CIRI). Dynamin-Related Protein 1 (Drp1), a pivotal regulator in the mitochondrial fission pathway, is an important substrate for SUMO2/3 modification. However, effects of SCH on SUMO2/3 modification of Drp1 remain undefined. Herein, the current study posits that SCH augments the SUMO2/3 modification of Drp1, thereby preserving mitochondrial integrity and mitigating CIRI.</div></div><div><h3>Methods</h3><div>A focal CIRI model was established in Sprague-Dawley rats, with 20°C saline perfused via the transcarotid artery to induce SCH condition, and 37°C saline serving as a control. The modified Neurological Severity Score (mNSS) was used to quantitate the degree of neurological deficits. Staining of 2,3–5-triphenyltetrazolium chloride (TTC) was performed to detect cerebral infarction volume. Histological change of neurocyte was observed through Hematoxylin-eosin (HE) staining. Neurocyte apoptosis was evaluated using terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) immunofluorescence staining. Western blot (WB) was utilized to evaluated the expressions of Drp1 and Cytochrome C. Co-immunoprecipitation was performed to evaluate the level of SUMO2/3 modification of Drp1. And transmission electron microscopy was used to observe the mitochondrial ultrastructure. The ratio of M-Drp1 to T-Drp1 and mitochondria morphological changes were observed under confocal microscopy.</div></div><div><h3>Results</h3><div>Research data revealed that SCH significantly enhanced the SUMO2/3 modification of Drp1 when CIRI occurred. Concurrently, mNSSs, cerebral infarct volume, and apoptotic rates were notably attenuated in the SCH group, corroborating SCH's protective role. Expression levels of mitochondrial outer membrane Drp1 (M-Drp1), cytoplasmic cytochrome C (C-CytC), and ratio of M-Drp1 to T-Drp1 were reduced, and changes of mitochondrial ultrastructural and morphology were mitigated, underscoring SCH's inhibitory effect on mitochondrial fission. In contrast, 37°C saline displayed negligible protective impact while compare with 20°C saline perfusion.</div></div><div><h3>Conclusions</h3><div>The findings support that SCH amplifies SUMO2/3 modification of Drp1, curtails excessive mitochondrial fission, and consequently ameliorates focal CIRI in a rat model.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"182 ","pages":"Article 106772"},"PeriodicalIF":3.4,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143681915","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory role of TEX10 gene in proliferation differentiation and apoptosis of bovine myoblasts","authors":"Yongpan Wang ,&nbsp;Zijing Zhang ,&nbsp;Yuqiao Zhang ,&nbsp;Jiamei Wang ,&nbsp;Shijie Lyu ,&nbsp;Xian Liu ,&nbsp;Xingshan Qi ,&nbsp;Weidong Ma ,&nbsp;Chuzhao Lei ,&nbsp;Eryao Wang ,&nbsp;Yongzhen Huang","doi":"10.1016/j.biocel.2025.106771","DOIUrl":"10.1016/j.biocel.2025.106771","url":null,"abstract":"<div><div>Skeletal muscle is a crucial tissue involved in body movement and energy metabolism, and its growth and development directly influence the economic value of livestock. This study investigates the effects of the <em>TEX10</em> gene on the proliferation, differentiation, and apoptosis of bovine myoblasts, as well as the underlying molecular mechanisms. Using techniques such as CCK-8, EdU incorporation, qPCR, Western blotting, and immunofluorescence, we observed that <em>TEX10</em> significantly promotes the expression of cell cycle factors, including <em>CDK2</em> and <em>PCNA</em>, thereby increasing cell proliferation and the proportion of cells in the S phase. Overexpression and knockdown experiments demonstrated that <em>TEX10</em> enhances the differentiation and myotube formation of myoblasts, while upregulating key genes such as <em>MYOG</em> and <em>MYOD</em>. Additionally, flow cytometry analysis of the cell cycle revealed that <em>TEX10</em> inhibits apoptosis in bovine myoblasts. Transcriptomic analysis showed that <em>TEX10</em> regulates several signaling pathways associated with proliferation, differentiation, and apoptosis, including PI3K-Akt, cAMP, and IL-17. Overall, these findings suggest that <em>TEX10</em> plays a significant regulatory role in bovine muscle growth, providing a theoretical foundation for molecular breeding strategies aimed at improving yellow cattle.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"182 ","pages":"Article 106771"},"PeriodicalIF":3.4,"publicationDate":"2025-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143630907","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identify key genes and biological processes participated in obesity-related cancer based on studying 12 cancers","authors":"Lijuan Zhu ,&nbsp;Cuicui Zhao","doi":"10.1016/j.biocel.2025.106764","DOIUrl":"10.1016/j.biocel.2025.106764","url":null,"abstract":"<div><div>Obesity significantly increases the risk of various diseases, particularly cancers, which present a serious threat to public health. Therefore, identifying cancers related to obesity and exploring their pathological pathways and key genes are highly significant for the prevention and treatment of these cancers. In this study, we propose the obesity and cancer edge connectivity based on expanded modular disease genes and expanded modular networks (OCEC_eDMN) algorithm, which based on the disease-related genes, Biological Process (BP) genes, and Protein-Potein Interaction (PPI) network. The algorithm utilizes Random Walk with Restart (RWR) to expand BP genes and disease genes to generate the expanded modular networks (eMNs) and disease genes (eMDs). Finally, this algorithm calculates the average interaction number between eMDs on eMNs. We utilize OCEC_eDMN to predict the ranking of 12 cancers related to obesity/morbid obesity and obtain an AUC of 0.93/0.84. Additionally, OCEC_eDMN reveals the significant BPs associated with obesity-cancer connections. For instance, \"gluconeogenesis\" plays a critical role in the connections between obesity and cancers. Through key driver analysis (KDA) on eMDs, we identify the key connectors in obesity-cancer connections. Genes such as GRB2 are instrumental in linking morbid obesity to colorectal cancer in the eMNs of “response to molecule of bacterial origin”. The significant eMNs and key genes provide valuable references for the prevention and treatment of obesity-related cancers and carry important theoretical implications.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"182 ","pages":"Article 106764"},"PeriodicalIF":3.4,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143537849","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SIRT2 inhibition attenuates myofibroblast transition through autophagy-mediated ciliogenesis in renal epithelial cells","authors":"Juyoung Son ,&nbsp;Jaejung Park ,&nbsp;Joo-Won Jeong ,&nbsp;Seung Hyeun Lee ,&nbsp;Ja-Eun Kim","doi":"10.1016/j.biocel.2025.106754","DOIUrl":"10.1016/j.biocel.2025.106754","url":null,"abstract":"<div><div>Myofibroblast transition plays a crucial role in both fibrotic diseases and wound healing. Although SIRT2 regulates fibrosis, its mechanisms of action remain poorly understood. This study aimed to investigate the effects of SIRT2 inhibition on myofibroblast transition in human renal cells under quiescent conditions. HK-2 kidney proximal tubular epithelial cells were starved of serum, resulting in the formation of primary cilia. Transforming growth factor-β (TGF-β) stimulation reduced both the number of ciliated cells and ciliary length. The ciliary defects resulted from a failure in autophagy termination, leading to the accumulation of OFD1, a negative regulator of ciliogenesis, at centriolar satellites. This phenomenon was correlated with the upregulation of fibrosis-related proteins. To elucidate the role of SIRT2 in the autophagy−ciliogenesis−fibrosis axis, cells were treated with AGK2, a specific inhibitor of SIRT2. AGK2 treatment promoted the formation of both autophagosomes and autolysosomes and facilitated OFD1 degradation at the centriolar satellites, resulting in the lengthening of primary cilia. Restoration of primary cilia by AGK2 was associated with the suppression of myofibroblast transition. In conclusion, SIRT2 inhibition attenuates TGF-β-induced fibrosis by promoting autophagy-mediated ciliogenesis. This study highlights SIRT2 as a potential therapeutic target for fibrotic diseases.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"181 ","pages":"Article 106754"},"PeriodicalIF":3.4,"publicationDate":"2025-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143484267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enhancement of wound healing in diabetic mice by topical use of a peptide-ionic liquid conjugate","authors":"Ana Gomes ,&nbsp;Ermelindo C. Leal ,&nbsp;Jessica Da Silva ,&nbsp;Inês Teixeira ,&nbsp;Ricardo Ferraz ,&nbsp;Daniela Calheiros ,&nbsp;Teresa Gonçalves ,&nbsp;Eugénia Carvalho ,&nbsp;Paula Gomes","doi":"10.1016/j.biocel.2025.106753","DOIUrl":"10.1016/j.biocel.2025.106753","url":null,"abstract":"<div><div>Diabetic foot ulcers (DFU) are one of the most devastating complications of diabetes, with high impact on patient’s quality of life. In worst scenarios, DFU can lead to severe amputation or even death. DFUs are an easy target for microbial pathogens and their effective healing is hampered by the galloping increase of microbial resistance to antibiotics, including from the most prevalent pathogens in DFU, <em>e.g. Staphylococcus aureus</em>. As such, available antibiotics show poor efficacy in the treatment of DFU, leading to a chronic condition that is exacerbated by poor healing rates due to the persistent inflammation, poor oxygenation and low angiogenesis, leading to high risk of ischemia, among other conditions that typically affect patients with diabetes. Our group has recently designed new peptide-based strategies towards the topical treatment of DFU, whereby peptide-ionic liquid conjugates emerged as highly promising agents. One of the best such conjugates, C₁₆-Im-PP4, results from coupling an imidazolium-based ionic liquid with intrinsic antimicrobial activity to the <em>N</em>-terminus of a collagen boosting peptide used in cosmetics, the pentapeptide-4. C₁₆-Im-PP4 showed excellent <em>in vitro</em> properties, namely, wide-spectrum antimicrobial action and collagen-boosting effect on human dermal fibroblasts, prompting the <em>in vivo</em> study here reported. The peptide-ionic liquid conjugate was applied topically on wounds of mice with diabetes. The results show multitargeted actions, at a dose of 1 µg/wound including: i) anti-inflammatory; ii) antioxidant; iii) pro-collagenic; vi) pro-angiogenic; v) antimicrobial; and vi) improved wound maturation effects. Altogether, these results identify this technology as a novel topical treatment for DFU.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"180 ","pages":"Article 106753"},"PeriodicalIF":3.4,"publicationDate":"2025-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143419123","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Expression analysis of molecular chaperones associated with disaggregation complex in rotenone-induced Parkinsonian rat model","authors":"Tanu ,&nbsp;Minal Chaturvedi ,&nbsp;Siraj Fatima ,&nbsp;Smriti Singh Yadav ,&nbsp;Prabeen Kumar Padhy ,&nbsp;Saurabh Tiwari ,&nbsp;Kavita Seth ,&nbsp;Rajnish K. Chaturvedi ,&nbsp;Smriti Priya","doi":"10.1016/j.biocel.2025.106752","DOIUrl":"10.1016/j.biocel.2025.106752","url":null,"abstract":"<div><div>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterized by the aberrant aggregation and phosphorylation (ser129) of α-synuclein (α-syn, a presynaptic protein) which leads to the formation of pathogenic Lewy bodies. A critical factor in the pathogenesis of PD is the disruption of the cellular protein quality control system, where molecular chaperones and their co-chaperones are integral for mitigating proteotoxic stress. Although the role of molecular chaperones in PD and other protein aggregation diseases has been extensively investigated, the in vivo investigation of disaggregation chaperones, including HSP70, HSP105, and co-chaperone DNAJBs, remains relatively limited. The present study aims to elucidate the expression dynamics of the disaggregation molecular chaperones within the substantia nigra pars compacta of the rotenone-induced Parkinsonian rat model and its association with α-syn aggregation. The rotenone-treated rats exhibited significant behavioural symptoms, α-syn aggregation and degeneration of dopaminergic neurons, confirming the development of Parkinsonism. Significant upregulation of α-syn expression/phosphorylation and co-localization in TH+ve neurons in the SNpc of treated rats was observed. Further, the gene and protein analysis of HSP70, DNAJB6, and HSP105 were found to be upregulated and TH+ve neurons showed their co-localization with p-α-syn^ser129 expression. The total proteomic analysis of SNpc correlated the altered cellular processes with cellular homeostasis imbalance. The observations of the present study provide an in vivo analysis of disaggregation-associated molecular chaperones in Parkinsonian or α-syn related conditions. The study can be helpful for further manipulation in the expression or activity of disaggregation-related chaperones for advanced therapeutic strategies and mechanistic studies in protein aggregation-associated diseases.</div></div>","PeriodicalId":50335,"journal":{"name":"International Journal of Biochemistry & Cell Biology","volume":"181 ","pages":"Article 106752"},"PeriodicalIF":3.4,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}