Biological Research最新文献

{"title":"Perturbation of mammary epithelial cell apicobasal polarity by RHBDF1-facilitated nuclear translocation of PKCζ.","authors":"Huan-Yu Zhao, Yi-Pan Zhu, Ying Wen, Jing Sun, Xin-Yu Ding, Xin-Yu Cao, Kai-Liang Wu, Li Fu, Lu-Yuan Li","doi":"10.1186/s40659-024-00566-2","DOIUrl":"10.1186/s40659-024-00566-2","url":null,"abstract":"<p><strong>Background: </strong>The establishment of apicobasal polarity in epithelial cells is of critical importance in morphogenesis of mammary gland and other secretive gland tissues. The demise of the polarity is a critical step in early stages of tumorigenesis such as in breast ductal carcinoma in situ. The underlying molecular mechanism thus warrants in-depth investigations.</p><p><strong>Results: </strong>Protein kinase C isoform ζ (PKCζ), which is highly expressed in breast cancer cells, accumulates in the nuclei of human mammary epithelial cells overexpressing human rhomboid family-1 (RHBDF1), an endoplasmic reticulum membrane protein. Nuclear translocation of PKCζ results in the failure of the formation of the cytosolic apicobasal polarity complex Par, of which PKCζ is an essential component. Additionally, enhanced nuclear translocation of PKCζ is accompanied by an inhibition of the expression of cell tight junction and adherens junction proteins and an increase of cell mobility. Mechanistically, RHBDF1 is able to interact with importin β1 and PKCζ and promote PKCζ phosphorylation. Consistently, treatment of RHBDF1-overexpressing cells with an inhibitor of PKCζ phosphorylation leads to restoration of apicobasal polarity and cell-cell junctions, as well as suppressed cell mobility.</p><p><strong>Conclusions: </strong>RHBDF1-facilitated nuclear translocation of PKCζ is critically responsible for the dismantlement of epithelial cell apicobasal polarity, and thus may serve as a target in the development of therapeutic approaches against early stages of breast cancer.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"90"},"PeriodicalIF":4.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587606/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Study on the therapeutic potential of induced neural stem cells for Alzheimer's disease in mice.","authors":"Qiongqiong Ji, Yuanhao Lv, Bei Hu, Yue Su, Imran Ibrahim Shaikh, Xu Zhu","doi":"10.1186/s40659-024-00568-0","DOIUrl":"10.1186/s40659-024-00568-0","url":null,"abstract":"<p><p>Induced neural stem cells (iNSCs), which have similar properties to neural stem cells and are able to self-proliferate and differentiate into neural cell lineages, are expected to be potential cells for the treatment of neurodegeneration disease. However, cell therapy based on iNSCs transplantation is limited by the inability to acquire sufficient quantities of iNSCs. Previous studies have found that mouse and human fibroblasts can be directly reprogrammed into iNSCs with a single factor, Sox2. Here, we induced mouse embryonic fibroblasts (MEFs) into iNSCs by combining valproic acid (VPA) with the induction factor Sox2, and the results showed that VPA significantly improved the conversion efficiency of fibroblasts to iNSCs. The iNSCs exhibited typical neurosphere-like structures that can express NSCs markers, such as Sox2, Nestin, Sox1, and Zbtb16, and could differentiate into neurons, astrocytes, and oligodendrocytes in vitro. Subsequently, the iNSCs were stereotactically transplanted into the hippocampus of APP/PS1 double transgenic mice (AD mice). Post-transplantation, the iNSCs showed long-term survival, migrated over long distances, and differentiated into multiple types of functional neurons and glial cells in vivo. Importantly, the cognitive abilities of APP/PS1 mice transplanted with iNSCs exhibited significant functional recovery. These findings suggest that VPA enhances the conversion efficiency of fibroblasts into iNSCs when used in combination with Sox2, and iNSCs hold promise as a potential donor material for transplantation therapy in Alzheimer's disease.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"89"},"PeriodicalIF":4.3,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11587668/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142709154","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effect of chronic exogenous oxytocin administration on exercise performance and cardiovagal control in hypobaric hypoxia in rats.","authors":"Camila Salazar-Ardiles, Carlos Cornejo, Cristobal Paz, Manuel Vasquez-Muñoz, Alexis Arce-Alvarez, Maria Rodriguez-Fernandez, Gregoire P Millet, Mikel Izquierdo, David C Andrade","doi":"10.1186/s40659-024-00573-3","DOIUrl":"10.1186/s40659-024-00573-3","url":null,"abstract":"<p><strong>Background: </strong>Outstanding exercise performance has been associated with an exacerbated vagal outflow. Nevertheless, during high-altitude hypobaric-hypoxia (HH), there is a baroreflex-dependent parasympathetic withdrawal and exercise performance deterioration. Notably, vagal control is pivotal in exercise performance, and exogenous oxytocin (OXY) administration has been shown to enhance parasympathetic drive; however, no evidence shows their role in exercise performance during HH. Then, this study aimed to examine the effect of prolonged exogenous oxytocin (OXY) administration on exercise performance during hypobaric hypoxia (HH) in rats.</p><p><strong>Results: </strong>A vehicle group (n = 6) and an OXY group (n = 6) performed incremental exercise and baroreflex tests during both normobaric normoxia (NN) and HH (PO₂: 100 mmHg, simulated 3,500 m) prior (pre-) and after (post-) 14 days of administration. The results showed that at pre-, there were no significant differences in exercise performance between the two groups, while at post-, the OXY group exhibited similar performance between NN and HH, while the Vehicle group maintained a significant decline in performance at HH compared to NN. At post-, the Vehicle group also demonstrated a reset in the baroreflex and a worse bradycardic response in HH, which was reversed in the OXY group, while the hypoxic ventilatory response was similar in both groups.</p><p><strong>Conclusion: </strong>The findings suggest prolonged OXY administration prevents impaired exercise performance and vagal control during short-term HH.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"88"},"PeriodicalIF":4.3,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11585223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142692371","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Depression like-behavior and memory loss induced by methylglyoxal is associated with tryptophan depletion and oxidative stress: a new in vivo model of neurodegeneration.","authors":"Md Samsuzzaman, Seong-Min Hong, Jae Hyuk Lee, Hyunjun Park, Keun-A Chang, Hyun-Bum Kim, Myoung Gyu Park, Hyeyoon Eo, Myung Sook Oh, Sun Yeou Kim","doi":"10.1186/s40659-024-00572-4","DOIUrl":"10.1186/s40659-024-00572-4","url":null,"abstract":"<p><strong>Background: </strong>Depression and memory loss are prevalent neurodegenerative disorders, with diabetic patients facing an elevated risk of brain dysfunction. Methylglyoxal (MGO) formation, which is heightened in diabetes owing to hyperglycemia and gut dysbiosis, may serve as a critical link between diabetes and brain diseases. Despite the high prevalence of MGO, the precise mechanisms underlying MGO-induced depression and memory loss remain unclear.</p><p><strong>Results: </strong>We investigated the effect of MGO stress on depression like-behavior and memory loss to elucidate the potential interplay between MGO-induced tryptophan (Trp) metabolism impairment and oxidative stress in the brain. It demonstrates that MGO induces depression-like behavior in mice, as confirmed by the OFT, TST, FST, SPT, and EPM behavioral tests. MGO led to the depletion of Trp and related neurotransmitters as 5-HT, EPI, and DA in the mouse brain. Additionally, MGO reduced the cell count in the DG, CA1, and CA3 hippocampal regions and modulated TPH2 levels in the brain. Notably, co-treatment with MGO and Trp mirrored the effects observed after Trp-null treatment in neurons, including reduced TPH1 and TPH2 levels and inhibition of neuronal outgrowth. Furthermore, MGO significantly altered the expression of key proteins associated with neurodegeneration, such as p-Tau, p-GSK-3β, APP, oAβ, BDNF, NGF, and p-TrkB. Concurrently, MGO activated MAPKs through ROS induction, triggering a redox imbalance by downregulating Nrf-2, Ho-1, TXNRD1, Trx, Sirt-3, and Sirt-5 expression levels, NAD^+, and CAT activity in the mouse brain. This led to an accelerated neuroinflammatory response, as evidenced by increased expression of Iba-1, p-NF-κB, and the secretion of IL-6 and TNF-α. Importantly, Trp treatment ameliorated MGO-induced depression like-behavior and memory loss in mice and markedly mitigated increased expression of p-Tau, APP, p-ERK1/2, p-pJNK, and p-NF-κB in the brain. Likewise, Trp treatment also induced the expression of MGO detoxifying factors GLO-I and GLO-II and CAT activity, suggesting the induction of an antioxidant system and reduced inflammation by inhibiting IL-6 and TNF-α secretion.</p><p><strong>Conclusions: </strong>Our data revealed that MGO-induced depression like-behavior and memory deficits resulted from disturbances in Trp, 5-HT, BDNF, and NGF levels, increased p-Tau and APP expression, neuroinflammation, and impaired redox status (Nrf-2/Ho-1/TXNRD1/Sirt3/5) in the brain.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"87"},"PeriodicalIF":4.3,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11580208/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142685922","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Overexpression of autophagy enhancer PACER/RUBCNL in neurons accelerates disease in the SOD1^G93A ALS mouse model.","authors":"Luis Labrador, Leonardo Rodriguez, Sebastián Beltran, Fernanda Hernandez, Laura Gomez, Patricia Ojeda, Cristian Bergmann, Melissa Calegaro-Nassif, Bredford Kerr, Danilo B Medinas, Patricio Manque, Ute Woehlbier","doi":"10.1186/s40659-024-00567-1","DOIUrl":"10.1186/s40659-024-00567-1","url":null,"abstract":"<p><p>Amyotrophic lateral sclerosis (ALS) is a debilitating and fatal paralytic disorder associated with motor neuron death. Mutant superoxide dismutase 1 (SOD1) misfolding and aggregation have been linked to familial ALS, with the accumulation of abnormal wild-type SOD1 species being also observed in postmortem tissue of sporadic ALS cases. Both wild-type and mutated SOD1 are reported to contribute to motoneuron cell death. The autophagic pathway has been shown to be dysregulated in ALS. Recent evidence suggests a dual time-dependent role of autophagy in the progression of the disease. PACER, also called RUBCNL (Rubicon-like), is an enhancer of autophagy and has been found diminished in its levels during ALS pathology in mice and humans. Pacer loss of function disturbs the autophagy process and leads to the accumulation of SOD1 aggregates, as well as sensitizes neurons to death. Therefore, here we investigated if constitutive overexpression of PACER in neurons since early development is beneficial in an in vivo model of ALS. We generated a transgenic mouse model overexpressing human PACER in neurons, which then was crossbred with the mutant SOD1^G93A ALS mouse model. Unexpectedly, PACER/SOD1^G93A double transgenic mice exhibited an earlier disease onset and shorter lifespan than did littermate SOD1^G93A mice. The overexpression of PACER in neurons in vivo and in vitro increased the accumulation of SOD1 aggregates, possibly due to impaired autophagy. These results suggest that similar to Pacer loss-of function, Pacer gain-of function is detrimental to autophagy, increases SOD1 aggregation and worsens ALS pathogenesis. In a wider context, our results indicate the requirement to maintain a fine balance of PACER protein levels to sustain proteostasis.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"86"},"PeriodicalIF":4.3,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571584/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646854","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Enrichment of trimethyl histone 3 lysine 4 in the Dlk1 and Grb10 genes affects pregnancy outcomes due to dietary manipulation of excess folic acid and low vitamin B12.","authors":"Divika Sapehia, Aatish Mahajan, Parampal Singh, Jyotdeep Kaur","doi":"10.1186/s40659-024-00557-3","DOIUrl":"10.1186/s40659-024-00557-3","url":null,"abstract":"<p><p>The aberrant expression of placental imprinted genes due to epigenetic alterations during pregnancy can impact fetal development. We investigated the impact of dietary modification of low vitamin B12 with varying doses of folic acid on the epigenetic control of imprinted genes and fetal development using a transgenerational model of C57BL/6J mice. The animals were kept on four distinct dietary combinations based on low vitamin B12 levels and modulated folic acid, mated in the F0 generation within each group. In the F1 generation, each group of mice is split into two subgroups; the sustained group was kept on the same diet, while the transient group was fed a regular control diet. After mating, maternal placenta (F1) and fetal tissues (F2) were isolated on day 20 of gestation. We observed a generation-wise opposite promoter CpG methylation and gene expression trend of the two developmental genes Dlk1 and Grb10, with enhanced gene expression in both the sustained and transient experimental groups in F1 placentae. When fetal development characteristics and gene expression were correlated, there was a substantial negative association between placental weight and Dlk1 expression (r = - 0.49, p < 0.05) and between crown-rump length and Grb10 expression (r = - 0.501, p < 0.05) in fetuses of the F2 generation. Consistent with these results, we also found that H3K4me3 at the promoter level of these genes is negatively associated with all fetal growth parameters. Overall, our findings suggest that balancing vitamin B12 and folic acid levels is important for maintaining the transcriptional status of imprinted genes and fetal development.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"85"},"PeriodicalIF":4.3,"publicationDate":"2024-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11562088/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614695","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Impact of salmon farming in the antibiotic resistance and structure of marine bacterial communities from surface seawater of a northern Patagonian area of Chile.","authors":"Javiera Ortiz-Severín, Christian Hodar, Camila Stuardo, Constanza Aguado-Norese, Felipe Maza, Mauricio González, Verónica Cambiazo","doi":"10.1186/s40659-024-00556-4","DOIUrl":"10.1186/s40659-024-00556-4","url":null,"abstract":"<p><strong>Background: </strong>Aquaculture and salmon farming can cause environmental problems due to the pollution of the surrounding waters with nutrients, solid wastes and chemicals, such as antibiotics, which are used for disease control in the aquaculture facilities. Increasing antibiotic resistance in human-impacted environments, such as coastal waters with aquaculture activity, is linked to the widespread use of antibiotics, even at sub-lethal concentrations. In Chile, the world's second largest producer of salmon, aquaculture is considered the primary source of antibiotics residues in the coastal waters of northern Patagonia. Here, we evaluated whether the structure and diversity of marine bacterial community, the richness of antibiotic resistance bacteria and the frequency of antibiotic resistance genes increase in communities from the surface seawater of an area with salmon farming activities, in comparison with communities from an area without major anthropogenic disturbance.</p><p><strong>Results: </strong>The taxonomic structure of bacterial community was significantly different between areas with and without aquaculture production. Growth of the culturable fraction under controlled laboratory conditions showed that, in comparison with the undisturbed area, the bacterial community from salmon farms displayed a higher frequency of colonies resistant to the antibiotics used by the salmon industry. A higher adaptation to antibiotics was revealed by a greater proportion of multi-resistant bacteria isolated from the surface seawater of the salmon farming area. Furthermore, metagenomics data revealed a significant higher abundance of antibiotic resistant genes conferring resistance to 11 antibiotic families in the community from salmon farms, indicating that the proportion of bacteria carrying the resistance determinants was overall higher in salmon farms than in the undisturbed site.</p><p><strong>Conclusions: </strong>Our results revealed an association between bacterial communities and antibiotic resistance from surface seawater of a coastal area of Chile. Although the total bacterial community may appear comparable between sites, the cultivation technique allowed to expose a higher prevalence of antibiotic resistant bacteria in the salmon farming area. Moreover, we demonstrated that metagenomics (culture-independent) and phenotypic (culture-dependent) methods are complementary to evaluate the bacterial communities' risk for antibiotic resistance, and that a human-influenced environment (such as salmon farms) can potentiate bacteria to adapt to environmental stresses, such as antibiotics.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"84"},"PeriodicalIF":4.3,"publicationDate":"2024-11-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552226/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142614706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EZH1/2 plays critical roles in oocyte meiosis prophase I in mice.","authors":"Ting Jiang, Chengxiu Zhang, Xinjing Cao, Yingpu Tian, Han Cai, Shuangbo Kong, Jinhua Lu, Haibin Wang, Zhongxian Lu","doi":"10.1186/s40659-024-00564-4","DOIUrl":"10.1186/s40659-024-00564-4","url":null,"abstract":"<p><strong>Backgroud: </strong>abnormalities or defects in oocyte meiosis can result in decreased oocyte quality, reduced ovarian reserve, and female diseases. However, the mechanisms of oocyte meiosis remain largely unknown, especially epigenetic regulation. Here, we explored the role of EZH1/2 (histone methyltransferase of H3K27) in mouse oocyte meiosis by inhibiting its activity and deleting its gene.</p><p><strong>Results: </strong>with embryonic ovary cultured in vitro, EZH1/2 was demonstrated to be essential for oocyte development during meiosis prophase I in mice. Activity inhibition or gene knockout of EZH1/2 resulted in cell apoptosis and a reduction in oocyte numbers within embryonic ovaries. By observing the expression of some meiotic marker protein (γ-H2AX, diplotene stage marker MSY2 and synapsis complex protein SCP1), we found that function deficiency of EZH1/2 resulted in failure of DNA double-strand breaks (DSBs) repair and break of meiotic progression in fetal mouse ovaries. Moreover, Ezh1/2 deficiency led to the suppression of ATM (Ataxia Telangiectasia Mutated kinase) phosphorylation and a decrease in the expression of key DNA repair proteins Hormad1, Mre11, Rad50, and Nbs1 in fetal mouse ovaries, underscoring the enzyme's pivotal role in initiating DNA repair. RNA-seq analysis revealed that Ezh1/2-deletion induced abnormal expression of multiple genes involved into several function of oocyte development in embryonic ovaries. Knockout of Ezh1/2 in ovaries also affected the levels of H3K9me3 and H4K20me2, as well as the expression of their target genes L3mbtl4 and Fbxo44.</p><p><strong>Conclusions: </strong>our study demonstrated that EZH1/2 plays a role in the DSBs repair in oocyte meiosis prophase I via multiple mechanisms and offers new insights into the physiological regulatory role of histone modification in fetal oocyte guardianship and female fertility.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"83"},"PeriodicalIF":4.3,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603106","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Phenotyping of a new yeast mapping population reveals differences in the activation of the TORC1 signalling pathway between wild and domesticated yeast strains.","authors":"Guilherme Rocha, Melissa Gómez, Camila Baeza, Francisco Salinas, Claudio Martínez, Eduardo I Kessi-Pérez","doi":"10.1186/s40659-024-00563-5","DOIUrl":"10.1186/s40659-024-00563-5","url":null,"abstract":"<p><p>Domestication can be understood as a symbiotic relationship that benefits both domesticator and domesticated species, involving multiple genetic changes that configure the phenotype of the domesticated species. One of the most important domesticated species is the yeast Saccharomyces cerevisiae, with both domesticated strains used for different fermentations processes for thousands of years and wild strains existing only in environments without human intervention; however, little is known about the phenotypic effects associated with its domestication. In the present work, we studied the effect of domestication on yeast TORC1 activation, a pleiotropic signalling pathway conserved across the eukaryotic domain. To achieve this goal, we improved a previously generated methodology to assess TORC1 activation, which turned out to be as effective as the original one but also presents several practical advantages for its application (such as facilitating confirmation of transformants and putting the Luc reporter gene under the control of the same P_RPL26A promoter for each transformed strain). We then generated a mapping population, the so-called TOMAN-G population, derived from the \"1002 Yeast Genomes Project\" population, the most comprehensive catalogue of the genetic variation in yeasts. Finally, strains belonging to the TOMAN-G population were phenotyped for TORC1 activation, and then we compared the results obtained between yeast strains with different ecological origins, finding differences in TORC1 activation between wild and domesticated strains, particularly wine strains. These results are indicative of the effect of domestication on TORC1 activation, specifically that the different evolutionary trajectories of wild and domesticated strains have in fact caused differences in the activation of this pathway; furthermore, the phenotypic data obtained in this work could be used to continue underlying the genetic bases of TORC1 activation, a process that is still not fully understood, using techniques such as GWAS to search for specific genetic variants underlying the observed phenotypic variability and phylogenetic tree inferences to gain insight into the evolutionary relationships between these genetic variants.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"82"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11545388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142603128","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"GLUT1 and prorenin receptor mediate differential regulation of TGF-β and CTGF in renal inner medullary collecting duct cells during high glucose conditions.","authors":"Paulina E Larenas, Pilar Cárdenas, Monserrat Aguirre-Delgadillo, Carlos Moris, Dulce E Casarini, Zoe Vallotton, Minolfa C Prieto, Alexis A Gonzalez","doi":"10.1186/s40659-024-00560-8","DOIUrl":"10.1186/s40659-024-00560-8","url":null,"abstract":"<p><strong>Background: </strong>During diabetes, prorenin is highly produced by the renal collecting ducts. The binding of prorenin to (pro)renin receptor (PRR) on the apical plasma membrane triggers intracellular profibrotic genes, including TGF-β and CTGF. However, the underlying mechanisms contributing to the stimulation of these pathways remain unclear. Hence, we hypothesize that the glucose transporter-1 (GLUT1) favors the PRR-dependent stimulation of TGF-β and CTGF in the distal nephron segments during high glucose (HG) conditions.</p><p><strong>Methods: </strong>To test this hypothesis, primary cultured renal inner medullary collecting duct (IMCD) cells were treated with normal glucose (NG, 5 mM) or high glucose (HG, 25 mM) for 48 h in the presence or absence of the GLUT1-specific inhibitor BAY 876 (2 nM). Additionally, IMCD cells were treated with the PRR antagonist PRO20. The expression of TGF-β and CTGF was quantified by immunoblot and qRT-PCR.</p><p><strong>Results: </strong>HG increased GLUT1 mRNA and protein abundance, while BAY 876 inhibited these responses. HG treatment upregulated PRR, but the concomitant treatment with BAY 876 partially prevented this effect. TGF-β and CTGF expressions were augmented in IMCD cells treated with HG. However, PRO20 prevented the increases in TGF-β but not those of CTGF. GLUT1 inhibition partially prevented the increases in reactive oxygen species (ROS) during HG while PRO20 did not. ROS scavenging impaired CTGF upregulation during HG conditions. Additionally, long-term exposure to HG increases lipid peroxidation and reduced cell viability.</p><p><strong>Conclusions: </strong>The data indicate that glucose transportation via GLUT1 is implicated in the PRR-dependent upregulation of TGF-β while CTGF is mediated mainly via a mechanism depending on ROS formation in renal medullary collecting duct cells.</p>","PeriodicalId":9084,"journal":{"name":"Biological Research","volume":"57 1","pages":"81"},"PeriodicalIF":4.3,"publicationDate":"2024-11-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11542404/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142590092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}