Cellular Physiology and Biochemistry最新文献

{"title":"Curbing Breast Cancer by Altering V-ATPase Action on F-Actin, Heterochromatin, ETV7 and mTORC2 Signaling.","authors":"Zeina S Khan, Fazle Hussain","doi":"10.33594/000000706","DOIUrl":"10.33594/000000706","url":null,"abstract":"<p><strong>Background/aims: </strong>Motivated by the vacuolar proton pump's importance in cancer, we investigate the effects of proton pump inhibition on breast cancer cell migration and proliferation, F-actin polymerization, lamin A/C, heterochromatin, and ETV7 expressions, nuclear size and shape, and AKT/mTOR signaling.</p><p><strong>Methods: </strong>Lowly metastatic MCF7 and highly metastatic MDA-MB-231 breast cancer cells were treated with 120 nM of proton pump inhibitor Bafilomycin A1 for 24 hours. Cell migration was studied with wound- scratch assays, ATP levels with a chemiluminescent assay; cell proliferation was quantified by a cell area expansion assay. Nuclear size and shape were determined using DAPI nuclear stain and fluorescence microscopy. The levels of F-actin, lamin A/C, heterochromatin, and ETV7 were quantified using both immunocytochemistry and western blots; p-mTORC1, p-mTORC2, mTOR, p-AKT, and AKT were measured by western blots.</p><p><strong>Results: </strong>We reveal that proton pump inhibition reduces F-actin polymerization, cell migration, proliferation, and increases heterochromatin in both lowly and highly metastatic cells. Surprisingly, Bafilomycin decreases lamin A/C in both cell lines. Inhibition has different effects on ETV7 expression in lowly and highly metastatic cells, as well as nuclear area, perimeter, and circularity. Bafilomycin also significantly decreases p-mTORC1, p-MTORC2, and MTOR expression in both cell lines, whereas it significantly decreases p-AKT in lowly metastatic cells and surprisingly significantly increases p-AKT in highly metastatic cells. Our proton pump inhibition protocol reduces V-ATPase levels (~25%) within three hours. V-ATPase levels vary in time for both control and inhibited cells, and inhibition reduces cellular ATP.</p><p><strong>Conclusion: </strong>Proton pumps promote F-actin polymerization and decrease heterochromatin, facilitating invasion. These pumps also upregulate both mTORC1 and mTORC2, thus highlighting the relevance of vacuolar proton pumps as metastatic cancer targets.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 3","pages":"250-272"},"PeriodicalIF":2.5,"publicationDate":"2024-06-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141310069","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adaptive Effects of Intermittent Hypoxia Training on Oxygen-Dependent Processes as a Potential Therapeutic Strategy Tool.","authors":"Natalia Kurhaluk, Oleksandr Lukash, Piotr Kamiński, Halina Tkaczenko","doi":"10.33594/000000705","DOIUrl":"https://doi.org/10.33594/000000705","url":null,"abstract":"<p><strong>Background/aims: </strong>Important benefits of intermittent hypoxic training (IHT) have emerged as an effective tool for enhancing adaptive potential in different pathological states, among which acute hypoxia dominates. Therefore, the aim of our study was to evaluate the mechanisms related to the effects of the nitric oxide system (nitrites, nitrates, carbamide, and total polyamine content) on ADP-stimulated oxygen consumption and oxidative phosphorylation in heart and liver mitochondria and biomarkers of oxidative stress in the blood, heart, and liver of rats exposed to the IHT method and acute hypoxia and treated with the amino acid L-arginine (600 mg/kg, 30 min) or the NO synthase inhibitor L-NNA (35 mg/kg, 30 min) prior to each IHT session.</p><p><strong>Methods: </strong>We analysed the modulation of the system of oxygen-dependent processes (mitochondrial respiration with the oxygraphic method, microsomal oxidation, and lipoperoxidation processes using biochemical methods) in tissues during IHT in the formation of short-term and long-term effects (30, 60, and 180 days after the last IHT session) with simultaneous administration of L-arginine. In particular, we investigated how mitochondrial functions are modulated during intermittent hypoxia with the use of oxidation substrates (succinate or α-ketoglutarate) in bioenergetic mechanisms of cellular stability and adaptation.</p><p><strong>Results: </strong>The IHT method is associated with a significant increase in the production of endogenous nitric oxide measured by the levels of its stable metabolite, nitrite anion, in both plasma (almost 7-fold) and erythrocytes (more than 7-fold) of rats. The intensification of nitric oxide-dependent pathways of metabolic transformations in the energy supply processes in the heart and liver, accompanied by oscillatory mechanisms of adaptation in the interval mode, causes a probable decrease in the production of urea and polyamines in plasma and liver, but not in erythrocytes. The administration of L-arginine prior to the IHT sessions increased the level of the nitrite-reducing component of the nitric oxide cycle, which persisted for up to 180 days of the experiment.</p><p><strong>Conclusion: </strong>Thus, the efficacy of IHT and its nitrite-dependent component shown in this study is associated with the formation of long-term adaptive responses by preventing the intensification of lipoperoxidation processes in tissues due to pronounced changes in the main enzymes of antioxidant defence and stabilisation of erythrocyte membranes, which has a pronounced protective effect on the system of regulation of oxygen-dependent processes as a whole.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 3","pages":"226-249"},"PeriodicalIF":0.0,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141300110","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000695","DOIUrl":"https://doi.org/10.33594/000000695","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"195"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907863","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction.","authors":"","doi":"10.33594/000000698","DOIUrl":"https://doi.org/10.33594/000000698","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"199"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000694","DOIUrl":"https://doi.org/10.33594/000000694","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"193-194"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907855","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction.","authors":"","doi":"10.33594/000000697","DOIUrl":"https://doi.org/10.33594/000000697","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"198"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Erratum.","authors":"","doi":"10.33594/000000696","DOIUrl":"https://doi.org/10.33594/000000696","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"196-197"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907890","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Retraction.","authors":"","doi":"10.33594/000000699","DOIUrl":"https://doi.org/10.33594/000000699","url":null,"abstract":"","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"200"},"PeriodicalIF":0.0,"publicationDate":"2024-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140907902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Acid-Sensitive Outwardly Rectifying Cl^- Current in OV2944 Mouse Ovarian Cancer Cells.","authors":"Hajime Hirasawa, Kayo Aoba, Naofumi Miwa","doi":"10.33594/000000692","DOIUrl":"https://doi.org/10.33594/000000692","url":null,"abstract":"<p><strong>Background/aims: </strong>Extracellular acidic conditions impair cellular activities; however, some cancer cells drive cellular signaling to adapt to the acidic environment. It remains unclear how ovarian cancer cells sense changes in extracellular pH. This study was aimed at characterizing acid-inducible currents in an ovarian cancer cell line and evaluating the involvement of these currents in cell viability.</p><p><strong>Methods: </strong>The biophysical and pharmacological properties of membrane currents in OV2944, a mouse ovarian cancer cell line, were studied using the whole-cell configuration of the patch-clamp technique. Viability of this cell type in acidic medium was evaluated using the MTT assay.</p><p><strong>Results: </strong>OV2944 had significant acid-sensitive outwardly rectifying (ASOR) Cl^- currents at a pH₅₀ of 5.3. The ASOR current was blocked by pregnenolone sulfate (PS), a steroid ion channel modulator that blocks the ASOR channel as one of its targets. The viability of the cells was reduced after exposure to an acidic medium (pH 5.3) but was slightly restored upon PS administration.</p><p><strong>Conclusion: </strong>These results offer first evidence for the presence of ASOR Cl^- channel in ovarian cancer cells and indicate its involvement in cell viability under acidic environment.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"172-181"},"PeriodicalIF":0.0,"publicationDate":"2024-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140848409","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pancreas Β-Cells in Type 1 and Type 2 Diabetes: Cell Death, Oxidative Stress and Immune Regulation. Recently Appearing Changes in Diabetes Consequences.","authors":"Elena G Novoselova, Sergey M Lunin, Maxim O Khrenov, Olga V Glushkova, Tatyana V Novoselova, Svetlana B Parfenyuk","doi":"10.33594/000000690","DOIUrl":"https://doi.org/10.33594/000000690","url":null,"abstract":"<p><p>Diabetes mellitus type 1 (T1D) and type 2 (T2D) develop due to dysfunction of the Langerhans islet β-cells in the pancreas, and this dysfunction is mediated by oxidative, endoplasmic reticulum (ER), and mitochondrial stresses. Although the two types of diabetes are significantly different, β-cell failure and death play a key role in the pathogenesis of both diseases, resulting in hyperglycemia due to a reduced ability to produce insulin. In T1D, β-cell apoptosis is the main event leading to hyperglycemia, while in T2D, insulin resistance results in an inability to meet insulin requirements. It has been suggested that autophagy promotes β-cell survival by delaying apoptosis and providing adaptive responses to mitigate the detrimental effects of ER stress and DNA damage, which is directly related to oxidative stress. As people with diabetes are now living longer, they are more susceptible to a different set of complications. There has been a diversification in causes of death, whereby a larger proportion of deaths among individuals with diabetes is attributable to nonvascular conditions; on the other hand, the proportion of cancer-related deaths has remained stable or even increased in some countries. Due to the increasing cases of both T1D and T2D, these diseases become even more socially significant. Hence, we believe that search for any opportunities for control of this disease is an overwhelmingly important target for the modern science. We focus on two differences that are characteristic of the development of diabetes's last periods. One of them shows that all-cause death rates have declined in several diabetes populations, driven in part by large declines in vascular disease mortality but large increases in oncological diseases. Another hypothesis is that some T2D medications could be repurposed to control glycemia in patients with T1D.</p>","PeriodicalId":9845,"journal":{"name":"Cellular Physiology and Biochemistry","volume":"58 2","pages":"144-155"},"PeriodicalIF":0.0,"publicationDate":"2024-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140863145","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}