Journal of Bioenergetics and Biomembranes最新文献

{"title":"Computational prediction of analog compounds of the membrane protein MCHR1 antagonists ALB-127158 and KRX-104130.","authors":"Emrah Sariyer, Ayşegül Saral Sariyer","doi":"10.1007/s10863-023-09993-4","DOIUrl":"10.1007/s10863-023-09993-4","url":null,"abstract":"<p><p>Obesity, which is already pervasive throughout the world, endangers public health by raising the prevalence of metabolic disorders and making their treatment more difficult. The development of drugs to treat obesity is a focus of effort. Melanin concentrated hormone receptor 1 (MCHR1) is the target of some of these therapeutic possibilities since as increased levels of melanin concentrated hormone have been found in obesity models. Known MCHR1 antagonists include BMS-830216, GW-856464, NGD-4715, ALB-127158, and AMG 076, but many have failed phase-I clinical studies. As a potential treatment for cardiotoxicity, KRX-104130 has only recently been identified. As MCH system is potentially effective target for treatment of obesity, in silico research into interaction between MCHR1 and its antagonists at molecular level was the primary goal of this study. Analogues ALB-127158 and KRX-104130 were screened among the RealEnamine library. The complexes obtained by molecular docking were embedded in mimics brain-cell membrane and simulated for 540 ns, and then MM-GBSA were calculated with MMPBSA.py. With all these computational studies, similar or different aspects of selected analogous compounds to ALB-127158 and KRX-104130 were investigated. The specificity of this study was that it analyzed MCHR1 protein as embedded in membrane. It was concluded that KRX-104130's analogue Z1922310273 and ALB-127158's analogue PV-002757495233 did not cause a difference in terms of phospholipid membrane properties. In addition, all ligands remained stable in putative binding site. It has been suggested that PV-002757495233 and Z1922310273 compounds can be evaluated as MCHR1 antagonists when all these outputs are considered in melting pots.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"435-446"},"PeriodicalIF":3.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71521559","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mir-25-3p in extracellular vesicles from fibroblast-like synoviocytes alleviates pyroptosis of chondrocytes in knee osteoarthritis.","authors":"Jianhang Wang,&nbsp;Tao Sun","doi":"10.1007/s10863-023-09964-9","DOIUrl":"https://doi.org/10.1007/s10863-023-09964-9","url":null,"abstract":"<p><p>Knee osteoarthritis (KOA) is defined as a joint disease that occurs mostly among elderly people. Fibroblast-like synoviocytes-derived extracellular vesicles (FLS-EVs) have impacts on the treatment of OA. This study elucidated the mechanism of miR-25-3p in pyroptosis of chondrocytes in KOA. FLSs and EVs were extracted from neonatal mice; destabilization of the medial meniscus (DMM) was used to simulate KOA in mice, followed by the evaluation of cartilage damage and the contents of MMP-3 and MMP-13 in KOA mice. Lipopolysaccharide (LPS) was used to induce inflammation damage in mouse chondrocytes ATDC5, and the cell viability and the expressions of NLRP3, Cleaved-Caspase-1, GSDMD-N, IL-18, and IL-1β were examined. We found that FLS-EV treatment mitigated the knee-joint damage and symptoms of KOA mice, decreased MMP-3 and MMP-13, and inhibited pyroptosis of chondrocytes in DMM mice and LPS-induced ATD5 cells. Then, Cy3-labeled miR-25-3p in mice chondrocytes was observed and the expressions and the binding relation of miR-25-3p and cytoplasmic polyadenylation element-binding protein 1 (CPEB1) were verified. It showed that FLS-EVs carried miR-25-3p into chondrocytes, and upregulated miR-25-3p expression while inhibited CPEB1 transcription, resulting in mitigation of pyroptosis of chondrocytes, and CPEB1 overexpression reversed the inhibition of FLS-EVs on pyroptosis of chondrocytes in KOA.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"55 5","pages":"365-380"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41112236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Blockage of PHLPP1 protects against myocardial ischemia/reperfusion injury in diabetic mice via activation of STAT3 signaling.","authors":"Sumin Gao,&nbsp;Yun Qiu,&nbsp;Yuming Meng,&nbsp;Yajuan Jia,&nbsp;Xuemei Lang,&nbsp;Hongmei Zhao,&nbsp;Hong Sun,&nbsp;Jinsong Zhang,&nbsp;Lianshu Ding","doi":"10.1007/s10863-023-09977-4","DOIUrl":"10.1007/s10863-023-09977-4","url":null,"abstract":"<p><p>Diabetes can exacerbate myocardial ischemia/reperfusion (IR) injury. However, the sensitivity to IR injury and the underlying mechanisms in diabetic hearts remain unclear. Inhibition of PH domain leucine-rich repeating protein phosphatase (PHLPP1) could reduce myocardial IR injury, our previous study demonstrated that the expression of PHLPP1 was upregulated in diabetic myocardial IR model. Thus, this study aimed to investigate the mechanism of PHLPP1 in diabetic myocardial IR injury. Nondiabetic and diabetic C57BL/6 mice underwent 45 min of coronary artery occlusion followed by 2 h of reperfusion. Male C57BL/6 mice were injected with streptozotocin for five consecutive days to establish a diabetes model. H9c2 cells were exposed to normal or high glucose and subjected to 4 h of hypoxia followed by 4 h of reoxygenation. Diabetes or hyperglycemia increased postischemic infarct size, cellular injury, release of creatine kinase-MB, apoptosis, and oxidative stress, while exacerbating mitochondrial dysfunction. This was accompanied by enhanced expression of PHLPP1 and decreased levels of p-STAT3 and p-Akt. These effects were counteracted by PHLPP1 knockdown. Moreover, PHLPP1 knockdown resulted in an increase in mitochondrial translocation of p-STAT3 Ser727 and nuclear translocation of p-STAT3 Tyr705 and p-STAT3 Ser727. However, the effect of PHLPP1 knockdown in reducing posthypoxic cellular damage was nullified by either Stattic or LY294002. Additionally, a co-immunoprecipitation assay indicated a direct interaction between PHLPP1 and p-STAT3 Ser727, but not p-STAT3 Tyr705. The abnormal expression of PHLPP1 plays a significant role in exacerbating myocardial IR injury in diabetic mice. Knockdown of PHLPP1 to activate the STAT3 signaling pathway may represent a novel strategy for alleviating myocardial IR injury in diabetes.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"325-339"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10007012","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hsa_circ_0052611 and mir-767-5p guide the warburg effect, migration, and invasion of BRCA cells through modulating SCAI.","authors":"Xin Wang,&nbsp;Zongwen Liu,&nbsp;Alan Chu,&nbsp;Rui Song,&nbsp;Shijia Liu,&nbsp;Ting Chai,&nbsp;Chen Sun","doi":"10.1007/s10863-023-09985-4","DOIUrl":"10.1007/s10863-023-09985-4","url":null,"abstract":"<p><p>Noncoding RNAs are key regulators in the Warburg Effect, an emerging hallmark of cancer. We intended to investigate the role and mechanism of circular RNA hsa_circ_0052611 (circ_0052611) and microRNA (miR)-767-5p in breast cancer (BRCA) hallmarks, especially the Warburg Effect. Expression of circ_0052611 and SCAI was downregulated, and miR-767-5p was upregulated in human BRCA tissues and cells; moreover, circ_0052611 acted as a miR-767-5p sponge to modulate the expression of miR-767-5p-targeted SCAI. Functionally, re-expressing circ_0052611 suppressed migration, invasion, glucose uptake, lactate production, and extracellular acidification rate (ECAR) in BRCA cells, and promoted apoptotic rate. These effects were accompanied by decreased Vimentin, N-cadherin, Bcl-2, and LDHA, and increased E-cadherin and Bax. Consistently, exhausting miR-767-5p exerted similar effects in BRCA cells. High miR-767-5p could counteract the role of circ_0052611 overexpression, and low SCAI likewise blocked the role of miR-767-5p deletion. In vivo, upregulating circ_0052611 delayed tumor growth of BRCA cells by altering miR-767-5p and SCAI expression. circ_0052611/miR-767-5p/SCAI axis might boycott the malignancy of BRCA cells.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"55 5","pages":"381-396"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41129768","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Propionic and valproic acids have an impact on bacteria viability, proton flux and ATPase activity.","authors":"Heghine Gevorgyan,&nbsp;Tamara Abaghyan,&nbsp;Margarita Mirumyan,&nbsp;Konstantin Yenkoyan,&nbsp;Karen Trchounian","doi":"10.1007/s10863-023-09983-6","DOIUrl":"10.1007/s10863-023-09983-6","url":null,"abstract":"<p><p>Short-chain fatty acids like propionic (PPA) and valproic acids (VP) can alter gut microbiota, which is suggested to play a role in development of autism spectrum disorders (ASD). In this study we investigated the role of various concentrations of PPA and VP in gut enteric gram-negative Escherichia coli K12 and gram-positive Enterococcus hirae ATCC 9790 bacteria growth properties, ATPase activity and proton flux. The specific growth rate (µ) was 0.24 h^-1 and 0.82 h^-1 in E. coli and E. hirae, respectively. Different concentrations of PPA reduced the value of µ similarly in both strains. PPA affects membrane permeability only in E. hirae. PPA decreased DCCD-sensitive ATPase activity in the presence of K⁺ ions by 20% in E. coli and 40% in E. hirae suggesting the importance of the F_OF₁-K⁺ transport system in the regulation of PPA-disrupted homeostasis. Moreover, the H⁺ flux during PPA consumption could be the protective mechanism for enteric bacteria. VP has a selective effect on the µ depending on bacteria. The overwhelming effect of VP was detected on the K⁺-promoted ATPase activity in E. hirae. Taken together it can be suggested that PPA and VP have a disruptive effect on E. coli and E. hirae growth, viability, bioenergetic and biochemical properties, which are connected with the alteration of F_OF₁-ATPase activity and H⁺ flux rate or direction.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"397-408"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10214761","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Toll-like receptor 4 promotes the inflammatory response in septic acute kidney injury by promoting p38 mitogen-activated protein kinase phosphorylation.","authors":"Linlin Yue,&nbsp;Xin Liu,&nbsp;Chaoyu Wu,&nbsp;Jiying Lai,&nbsp;Jie Wang,&nbsp;Huifeng Zhong,&nbsp;Feng Chen","doi":"10.1007/s10863-023-09972-9","DOIUrl":"10.1007/s10863-023-09972-9","url":null,"abstract":"<p><p>Septic acute kidney injury (AKI) contributes to the mortality and morbidity of sepsis patients. Toll-like Receptor 4 (TLR4) has prominent roles in septic AKI. This study investigated the functions of TLR4 in septic AKI. A septic AKI mouse model was established by cecal ligation and puncture surgery. Mouse kidney function and kidney tissue lesion were examined using corresponding kits and H&E staining. The in vitro cell model of septic AKI was established by lipopolysaccharide induction. Cell viability, inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, pyroptotic cell number changes, lactate dehydrogenase (LDH) activity, myeloperoxidase (MOP) concentration, and levels of pyroptosis-associated protein and MyD88, TRIF and p38 MAPK phosphorylation were determined by MTT, ELISA, FAM-FLICA Caspase-1 Detection kit, other corresponding kits, and Western blot. TLR4 was highly expressed in septic AKI mouse kidney tissues and human septic AKI cells. TLR4 knockdown alleviated kidney injury, increased cell viability, and reduced LDH activity and MPO concentration. TLR4 knockdown reduced cell pyroptosis by repressing p38 MAPK phosphorylation through MyD88/TRIF, suppressed pro-inflammatory factor (TNF-α, IL-6, IL-4, IL-1β, IL-18) levels, promoted anti-inflammatory factor (IL-4) level, and reduced inflammatory response, thus playing a protective role in septic AKI. Briefly, TLR4 promoted the inflammatory response in septic AKI by promoting p38 MAPK phosphorylation through MyD88/TRIF.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"353-363"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10556113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10414433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bidirectional negative feedback actions of DNMT3A and miR-145 in regulating autophagy in cardiac fibroblasts and affecting myocardial fibrosis.","authors":"Shucan Xu,&nbsp;Yonglin Zhang,&nbsp;Guangzhi Zhou,&nbsp;Aijun Liu","doi":"10.1007/s10863-023-09980-9","DOIUrl":"10.1007/s10863-023-09980-9","url":null,"abstract":"<p><p>Epigenetic regulation has crucial implications for myocardial fibrosis. It has been reported that autophagy, regulated by miR-145, is implicated in the proliferation and fibrosis of cardiac fibroblasts (CFs). However, how it works during the process remains unclear. This study explored the exact effects of epigenetic regulation of miR-145 expression on autophagy, proliferation, and fibrosis of CFs. To examine the expression levels of myocardial fibrosis markers (α-SMA and collagen I), autophagy-related proteins (LC3I, LC3II, p62), DNMT3A, and miR-145, qRT-PCR and western blot were employed. And the proliferation of CFs was detected by CCK-8 and ErdU. As for the determination of the binding relationship between DNMT3A and miR-145, dual-luciferase assay was conducted. Next, the detection of the methylation level of the pre-miR-145 promoter region was completed by MSP. And the verification of the effect of the DNMT3A/miR-145 axis on myocardial fibrosis was accomplished by constructing mouse myocardial infarction (MI) models based on the ligation of the left anterior descending method. In TGF-β1-activated CFs, remarkable up-regulation of DNMT3 and considerable down-regulation of miR-145 were observed. And further experiments indicated that DNMT3A was able to down-regulate miR-145 expression by maintaining the hypermethylation level of the pre-miR-145 promoter region. In addition, DNMT3A expression could be directly targeted and negatively modulated by miR-145. Moreover, in vitro cell experiments and mouse MI models demonstrated that DNMT3A overexpression could inhibit autophagy, and promote cell proliferation and fibrosis of CFs. However, this kind of effect could be reversed by miR-145 overexpression. In summary, myocardial fibroblast autophagy can be regulated by bidirectional negative feedback actions of DNMT3A and miR-145, thus affecting myocardial fibrosis. This finding will provide a potential target for the clinical treatment of myocardial fibrosis.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":" ","pages":"341-352"},"PeriodicalIF":3.0,"publicationDate":"2023-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10426950","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Purinergic receptor P2X7 activates NOX2/JNK signaling to participate in granulosa cell inflammation and apoptosis in polycystic ovary syndrome.","authors":"Chuan Shen,&nbsp;Yongmei Jiang,&nbsp;Jia Lin,&nbsp;Yibei He,&nbsp;Yue Liu,&nbsp;Dingzhi Fang","doi":"10.1007/s10863-023-09979-2","DOIUrl":"10.1007/s10863-023-09979-2","url":null,"abstract":"<p><p>Increasing evidence shows that polycystic ovary syndrome (PCOS) is often accompanied by an inflammatory response, hence, appropriately managing granulosa cell inflammation is critical to regaining ovarian function in PCOS. In this study, the differential levels of purinergic receptor P2X7 between the control and PCOS samples in the dataset GSE34526 were assessed, then PCOS mouse models were established. Following evaluating the fluctuations in hormone levels, inflammatory cytokines, and P2X7, mice received treatment with the P2X7 antagonist A740003. Its effects on hormones, inflammation, apoptosis, and NOX2 signaling in mice were examined. Afterward, primary mouse granulosa cells were isolated, and the mediating role of NOX2 signaling in the P2X7 regulatory pathway was confirmed by transfection of NOX2 overexpression plasmids. The results demonstrated that P2X7 was significantly elevated in the PCOS samples in the dataset. Compared with the control group, PCOS mice had significant differences in the follicle-stimulating hormone, luteinizing hormone, testosterone, anti-Müllerian hormone, inflammatory factors, and P2X7. Treatment with A740003 partially restored these parameter levels, including NOX2 signaling. Based on in vitro experiments on primary mouse granulosa cells, the above findings were re-verified, and the overexpression of NOX2 could reverse the regulatory function of P2X7. The present study highlights that P2X7 level increases in PCOS, and inhibition of P2X7 can reduce disease symptoms. It is involved in inflammation and apoptosis in granulosa cells through NOX2/JNK signaling.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"55 4","pages":"313-322"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10585609","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Circ_0001714 knockdown alleviates lipopolysaccharide-induced apoptosis and inflammation in renal tubular epithelial cells via miR-129-5p/TRAF6 axis in septic acute kidney injury.","authors":"Yiqing Tan,&nbsp;Ziying Yu,&nbsp;Pei Li,&nbsp;Yu Liu,&nbsp;Ting You,&nbsp;Feng Kuang,&nbsp;Wei Luo","doi":"10.1007/s10863-023-09975-6","DOIUrl":"10.1007/s10863-023-09975-6","url":null,"abstract":"<p><strong>Background: </strong>Circular RNAs (circRNAs) have been shown to play roles in regulating sepsis. Sepsis is a major cause of acute kidney injury (AKI). Herein, we aimed to investigate the role and mechanism of circ_0001714 in the progression of sepsis-induced AKI.</p><p><strong>Methods: </strong>Human HK-2 cells were exposed to lipopolysaccharide (LPS) for functional experiments. Quantitative real-time polymerase chain reaction and western blotting were used for expression analysis. Functional experiments were performed by using MTT assay, 5-ethynyl-2'-deoxyuridine assay, flow cytometry, and enzyme-linked immunosorbent assay (ELISA). The binding between miR-129-5p and circ_0001714 or TRAF6 (TNF receptor associated factor 6) was validated using dual-luciferase reporter assay.</p><p><strong>Results: </strong>Circ_0001714 expression was higher in sepsis-AKI patients. HK-2 cells were exposed to LPS to imitate the injury of renal tubular epithelial cells during sepsis-AKI. LPS dose-dependently up-regulated circ_0001714, moreover, circ_0001714 silencing reversed LPS-evoked apoptosis and inflammation in HK-2 cells. Mechanistically, circ_0001714 sequestered miR-129-5p to up-regulate TRAF6 expression, implying the circ_0001714/miR-129-5p/TRAF6 feedback loop. MiR-129-5p was decreased, while TRAF6 was increased in sepsis-AKI patients and LPS-stimulated HK-2 cells. MiR-129-5p re-expression or TRAF6 silencing protected against LPS-induced HK-2 cell apoptosis and inflammation. Additionally, a series of rescue experiments showed that miR-129-5p inhibition reversed the inhibitory action of circ_0001714 knockdown on LPS-induced HK-2 cell injury. Furthermore, TRAF6 overexpression also attenuated the protective effects of miR-129-5p on HK-2 cells under LPS treatment.</p><p><strong>Conclusion: </strong>Circ_0001714 silencing might alleviate LPS-induced apoptosis and inflammation via targeting miR-129-5p/TRAF6 axis in HK-2 cells.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"55 4","pages":"289-300"},"PeriodicalIF":3.0,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10227716","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"<ArticleTitle xmlns:ns0=\"http://www.w3.org/1998/Math/MathML\">Simulation of biochemical dynamics of <ns0:math>\u0000 <ns0:mi>C</ns0:mi>\u0000 <ns0:msup>\u0000 <ns0:mrow class=\"MJX-TeXAtom-ORD\">\u0000 <ns0:mi>a</ns0:mi>\u0000 </ns0:mrow>\u0000 <ns0:mrow class=\"MJX-TeXAtom-ORD\">\u0000 <ns0:mn>2</ns0:mn>\u0000 <ns0:mo>+</ns0:mo>\u0000 </ns0:mrow>\u0000 </ns0:msup>\u0000</ns0:math> and <ns0:math>\u0000 <ns0:mi>P</ns0:mi>\u0000 <ns0:mi>L</ns0:mi>\u0000 <ns0:mi>C</ns0:mi>\u0000</ns0:math> in fibroblast cell.","authors":"Ankit Kothiya, Neeru Adlakha","doi":"10.1007/s10863-023-09976-5","DOIUrl":"10.1007/s10863-023-09976-5","url":null,"abstract":"<p><p>Calcium dynamics is not only responsible for maintaining the framework and functions of the cell but also plays a role in the dynamics of other biochemical systems in the cell. Phospholipase C-<math>\u0000 <mi>γ</mi>\u0000</math> l (<math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math>) has a crucial role in the function of fibroblast cells. Experiments have shown that <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> and <math>\u0000 <mi>C</mi>\u0000 <msup>\u0000 <mrow>\u0000 <mi>a</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>2</mn>\u0000 <mo>+</mo>\u0000 </mrow>\u0000 </msup>\u0000</math> have interdependent dynamics in fibroblast cells. However, no reaction-diffusion model exists for the two-way feedback system dynamics of <math>\u0000 <mi>C</mi>\u0000 <msup>\u0000 <mrow>\u0000 <mi>a</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>2</mn>\u0000 <mo>+</mo>\u0000 </mrow>\u0000 </msup>\u0000</math> and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> in fibroblasts till date. The computational model is designed to investigate the impact of variations in several processes, such as the <math>\u0000 <mi>S</mi>\u0000 <mi>E</mi>\u0000 <mi>R</mi>\u0000 <mi>C</mi>\u0000 <mi>A</mi>\u0000</math> pump, buffer process, source inflow, etc., on the system dynamics of <math>\u0000 <mi>C</mi>\u0000 <msup>\u0000 <mrow>\u0000 <mi>a</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>2</mn>\u0000 <mo>+</mo>\u0000 </mrow>\u0000 </msup>\u0000</math> and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> in fibroblast cells. The computational findings are obtained using finite element techniques, and the consequences of dysregulation in various processes on the spatiotemporal calcium and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> dynamics in fibroblasts are investigated. The results lead to the conclusion that the effects of buffer, source influx, diffusion, and <math>\u0000 <mi>S</mi>\u0000 <mi>E</mi>\u0000 <mi>R</mi>\u0000 <mi>C</mi>\u0000 <mi>A</mi>\u0000</math> pump can cause fluctuations in the dynamics of <math>\u0000 <mi>C</mi>\u0000 <msup>\u0000 <mrow>\u0000 <mi>a</mi>\u0000 </mrow>\u0000 <mrow>\u0000 <mn>2</mn>\u0000 <mo>+</mo>\u0000 </mrow>\u0000 </msup>\u0000</math> and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> in fibroblasts. Disruptions in these constitutive processes can result in changes in the dynamics of calcium and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math>. Thus, the current model provides new/novel information regarding the precise dysregulatory constitutive systems that regulate calcium and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> kinetics, such as source inflow, diffusion, <math>\u0000 <mi>S</mi>\u0000 <mi>E</mi>\u0000 <mi>R</mi>\u0000 <mi>C</mi>\u0000 <mi>A</mi>\u0000</math>, and buffer, can be responsible for excessive calcium and <math>\u0000 <mi>P</mi>\u0000 <mi>L</mi>\u0000 <mi>C</mi>\u0000</math> concentrations leading to fibrotic illnesses such as cancer and fibrosis.</p>","PeriodicalId":15080,"journal":{"name":"Journal of Bioenergetics and Biomembranes","volume":"55 4","pages":"267-287"},"PeriodicalIF":2.9,"publicationDate":"2023-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10231202","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}