Channels (Austin, Tex.)最新文献_第3页

Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models. 瞬时受体电位1型香草素:糖尿病模型中的心脏保护作用。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-20 DOI: 10.1080/19336950.2023.2281743

Jiaqi Bao, Zhicheng Gao, Yilan Hu, Lifang Ye, Lihong Wang

{"title":"Transient receptor potential vanilloid type 1: cardioprotective effects in diabetic models.","authors":"Jiaqi Bao, Zhicheng Gao, Yilan Hu, Lifang Ye, Lihong Wang","doi":"10.1080/19336950.2023.2281743","DOIUrl":"10.1080/19336950.2023.2281743","url":null,"abstract":"Cardiovascular disease, especially heart failure (HF) is the leading cause of death in patients with diabetes. Individuals with diabetes are prone to a special type of cardiomyopathy called diabetic cardiomyopathy (DCM), which cannot be explained by heart diseases such as hypertension or coronary artery disease, and can contribute to HF. Unfortunately, the current treatment strategy for diabetes-related cardiovascular complications is mainly to control blood glucose levels; nonetheless, the improvement of cardiac structure and function is not ideal. The transient receptor potential cation channel subfamily V member 1 (TRPV1), a nonselective cation channel, has been shown to be universally expressed in the cardiovascular system. Increasing evidence has shown that the activation of TRPV1 channel has a potential protective influence on the cardiovascular system. Numerous studies show that activating TRPV1 channels can improve the occurrence and progression of diabetes-related complications, including cardiomyopathy; however, the specific mechanisms and effects are unclear. In this review, we summarize that TRPV1 channel activation plays a protective role in the heart of diabetic models from oxidation/nitrification stress, mitochondrial function, endothelial function, inflammation, and cardiac energy metabolism to inhibit the occurrence and progression of DCM. Therefore, TRPV1 may become a latent target for the prevention and treatment of diabetes-induced cardiovascular complications.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761101/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138178171","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Type 3 IP3 receptor: Its structure, functions, and related disease implications. 3型IP3受体：其结构、功能和相关疾病的意义。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI: 10.1080/19336950.2023.2267416

Lvying Wu, Jin Chen

引用次数: 0

The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment. ATP结合盒（ABC）转运蛋白在癌症中的作用：评估预后、预测免疫力和指导治疗。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-31 DOI: 10.1080/19336950.2023.2273247

Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu

{"title":"The role of ATP binding cassette (ABC) transporters in breast cancer: Evaluating prognosis, predicting immunity, and guiding treatment.","authors":"Yuan Yuan, Zhouhong Xiang, Yuhua Xia, Jiaheng Xie, Xiudi Jiang, Zhicheng Lu","doi":"10.1080/19336950.2023.2273247","DOIUrl":"10.1080/19336950.2023.2273247","url":null,"abstract":"Breast cancer is currently the most prevalent form of cancer worldwide. Nevertheless, there remains limited clarity regarding our understanding of the tumor microenvironment and metabolic characteristics associated with it. ATP-binding cassette (ABC) transporters are the predominant transmembrane transporters found in organisms. Therefore, it is essential to investigate the role of ABC transporters in breast cancer. Transcriptome data from breast cancer patients were downloaded from the TCGA database. ABC transporter-related genes were obtained from the Genecards database. By LASSO regression, ABC-associated prognostic signature was constructed in breast cancer. Subsequently, immune microenvironment analysis was performed. Finally, cell experiments were performed to verify the function of ABCB7 in the breast cancer cell lines MDA-MB-231 and MCF-7. Using the ABC transporter-associated signature, we calculated a risk score for each breast cancer patient. Patients with breast cancer were subsequently categorized into high-risk and low-risk groups, utilizing the median risk score as the threshold. Notably, patients in the high-risk group exhibited significantly worse prognosis (P<0.05). Additionally, differences were observed in terms of immune cell infiltration levels, immune correlations, and gene expression of immune checkpoints between the two groups. Functional experiments conducted on breast cancer cell lines MDA-MB-231 and MCF-7 demonstrated that ABCB7 knockdown significantly diminished cell activity, proliferation, invasion, and migration. These findings emphasize the significance of understanding ABC transporter-mediated metabolic and transport characteristics in breast cancer, offering promising directions for further research and potential therapeutic interventions.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761142/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71415686","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Fibrillin-1 mutation contributes to Marfan syndrome by inhibiting Cav1.2-mediated cell proliferation in vascular smooth muscle cells. 纤颤蛋白1突变通过抑制血管平滑肌细胞中cav1.2介导的细胞增殖而导致马凡氏综合征。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2192377

Wenfeng Lin, Jiaqi Xiong, Yefan Jiang, Hao Liu, Jinhui Bian, Juejin Wang, Yongfeng Shao, Buqing Ni

{"title":"Fibrillin-1 mutation contributes to Marfan syndrome by inhibiting Cav1.2-mediated cell proliferation in vascular smooth muscle cells.","authors":"Wenfeng Lin, Jiaqi Xiong, Yefan Jiang, Hao Liu, Jinhui Bian, Juejin Wang, Yongfeng Shao, Buqing Ni","doi":"10.1080/19336950.2023.2192377","DOIUrl":"10.1080/19336950.2023.2192377","url":null,"abstract":"Marfan syndrome (MFS) is an autosomal dominant connective tissue disorder caused by mutation in fibrillin-1 (FBN1). However, the molecular mechanism underlying MFS remains poorly understood. The study aimed to explore how the L-type calcium channel (CaV1.2) modulates disease progression of MFS and to identify a potential effective target for attenuating MFS. KEGG enrichment analysis showed that the calcium signaling pathway gene set was significantly enriched. We demonstrated that FBN1 deficiency exhibited inhibition on both the expression of Cav1.2 and proliferation of vascular smooth muscle cells (VSMCs). Then, we examined whether FBN1 mediates Cav1.2 via regulating TGF-β1. Higher levels of TGF-β1 were observed in the serum and aortic tissues from patients with MFS. TGF-β1 modulated Cav1.2 expression in a concentration-dependent manner. We evaluated the role of Cav1.2 in MFS by small interfering RNA and Cav1.2 agonist Bay K8644. The effect of Cav1.2 on cell proliferation was dependent on c-Fos activity. These results demonstrated FBN1 deficiency decreased the expression levels of Cav1.2 via regulation of TGF-β1, and downregulation of Cav1.2 inhibited cell proliferation of human aortic smooth muscle cells (HASMCs) in MFS patients. These findings suggest that Cav1.2 may be an appealing therapeutic target for MFS.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10054150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9567567","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Characterization of two pathological gating-charge substitutions in Cav1.4 L-type calcium channels. Cav1.4 l型钙通道中两种病理性门控电荷取代的表征。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2192360

Thomas Heigl, Michael A Netzer, Lucia Zanetti, Matthias Ganglberger, Monica L Fernández-Quintero, Alexandra Koschak

{"title":"Characterization of two pathological gating-charge substitutions in Cav1.4 L-type calcium channels.","authors":"Thomas Heigl, Michael A Netzer, Lucia Zanetti, Matthias Ganglberger, Monica L Fernández-Quintero, Alexandra Koschak","doi":"10.1080/19336950.2023.2192360","DOIUrl":"10.1080/19336950.2023.2192360","url":null,"abstract":"Cav1.4 L-type calcium channels are predominantly expressed at the photoreceptor terminals and in bipolar cells, mediating neurotransmitter release. Mutations in its gene, CACNA1F, can cause congenital stationary night-blindness type 2 (CSNB2). Due to phenotypic variability in CSNB2, characterization of pathological variants is necessary to better determine pathological mechanism at the site of action. A set of known mutations affects conserved gating charges in the S4 voltage sensor, two of which have been found in male CSNB2 patients. Here, we describe two disease-causing Cav1.4 mutations with gating charge neutralization, exchanging an arginine 964 with glycine (RG) or arginine 1288 with leucine (RL). In both, charge neutralization was associated with a reduction channel expression also reflected in smaller ON gating currents. In RL channels, the strong decrease in whole-cell current densities might additionally be explained by a reduction of single-channel currents. We further identified alterations in their biophysical properties, such as a hyperpolarizing shift of the activation threshold and an increase in slope factor of activation and inactivation. Molecular dynamic simulations in RL substituted channels indicated water wires in both, resting and active, channel states, suggesting the development of omega (ω)currents as a new pathological mechanism in CSNB2. This sum of the respective channel property alterations might add to the differential symptoms in patients beside other factors, such as genomic and environmental deviations.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10038055/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9539042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Effect of truncation on TRPM7 channel activity. 截断对TRPM7通道活性的影响。

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2200874

Zhuqing Xie, Nashat Abumaria

{"title":"Effect of truncation on TRPM7 channel activity.","authors":"Zhuqing Xie, Nashat Abumaria","doi":"10.1080/19336950.2023.2200874","DOIUrl":"10.1080/19336950.2023.2200874","url":null,"abstract":"Transient receptor potential melastatin-like 7 (TRPM7) is a key player in various physiological and pathological processes. TRPM7 channel activity is regulated by different factors. The effects of cleavage of different domains on channel activity remain unknown. Here, we constructed several TRPM7 clones and explored the effects of truncating the mouse TRPM7 at different locations on the ion channel activity in two cell lines. We compared the clones' activity with the full-length TRPM7 and the native TRPM7 in transfected and untransfected cells. We also expressed fluorescently tagged truncated clones to examine their protein stability and membrane targeting. We found that truncating the kinase domain induced reduction in TRPM7 channel activity. Further truncations beyond the kinase (serine/threonine rich domain and/or coiled-coil domain) did not result in further reductions in channel activity. Two truncated clones lacking the TRP domain or the melastatin homology domain had a completely nonfunctional channel apparently due to disruption of protein stability. We identified the shortest structure of TRPM7 with measurable channel activity. We found that the truncated TRPM7 containing only S5 and S6 domains retained some channel activity. Adding the TRP domain to the S5-S6 resulted in a significant increase in channel activity. Finally, our analysis showed that TRPM7 outward currents are more sensitive to truncations than inward currents. Our data provide insights on the effects of truncating TRPM7 at different locations on the channel functions, highlighting the importance of different domains in impacting channel activity, protein stability, and/or membrane targeting.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10761173/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9577031","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses. 生物信息学分析揭示了突触神经条件易感性途径和神经血管紧张素1相互作用组的重叠。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-08 DOI: 10.1080/19336950.2023.2253102

Simona D Frederiksen, Leigh E Wicki-Stordeur, Leigh Anne Swayne

{"title":"Overlap in synaptic neurological condition susceptibility pathways and the neural pannexin 1 interactome revealed by bioinformatics analyses.","authors":"Simona D Frederiksen, Leigh E Wicki-Stordeur, Leigh Anne Swayne","doi":"10.1080/19336950.2023.2253102","DOIUrl":"10.1080/19336950.2023.2253102","url":null,"abstract":"Many neurological conditions exhibit synaptic impairments, suggesting mechanistic convergence. Additionally, the pannexin 1 (PANX1) channel and signaling scaffold is linked to several of these neurological conditions and is an emerging regulator of synaptic development and plasticity; however, its synaptic pathogenic contributions are relatively unexplored. To this end, we explored connections between synaptic neurodevelopmental disorder and neurodegenerative disease susceptibility genes discovered by genome-wide association studies (GWASs), and the neural PANX1 interactome (483 proteins) identified from mouse Neuro2a (N2a) cells. To identify shared susceptibility genes, we compared synaptic suggestive GWAS candidate genes amongst autism spectrum disorders, schizophrenia, Parkinson's disease, and Alzheimer's disease. To further probe PANX1 signaling pathways at the synapse, we used bioinformatics tools to identify PANX1 interactome signaling pathways and protein-protein interaction clusters. To shed light on synaptic disease mechanisms potentially linking PANX1 and these four neurological conditions, we performed additional cross-analyses between gene ontologies enriched for the PANX1 synaptic and disease-susceptibility gene sets. Finally, to explore the regional specificity of synaptic PANX1-neurological condition connections, we identified brain region-specific elevations of synaptic PANX1 interactome and GWAS candidate gene set transcripts. Our results confirm considerable overlap in risk genes for autism spectrum disorders and schizophrenia and identify potential commonalities in genetic susceptibility for neurodevelopmental disorders and neurodegenerative diseases. Our findings also pinpointed novel putative PANX1 links to synaptic disease-associated pathways, such as regulation of vesicular trafficking and proteostasis, warranting further validation.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10563626/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41157876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 3

Molecular pharmacology of the onco-TRP channel TRPV6. 肿瘤TRP通道TRPV6的分子药理学。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-10-15 DOI: 10.1080/19336950.2023.2266669

Arthur Neuberger, Alexander I Sobolevsky

引用次数: 0

L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development. l型钙通道与神经精神疾病:遗传风险变异相关的基因组调控及其对大脑发育的影响

Channels (Austin, Tex.) Pub Date : 2023-12-01 DOI: 10.1080/19336950.2023.2176984

Madelyn R Baker, Andrew S Lee, Anjali M Rajadhyaksha

{"title":"L-type calcium channels and neuropsychiatric diseases: Insights into genetic risk variant-associated genomic regulation and impact on brain development.","authors":"Madelyn R Baker, Andrew S Lee, Anjali M Rajadhyaksha","doi":"10.1080/19336950.2023.2176984","DOIUrl":"10.1080/19336950.2023.2176984","url":null,"abstract":"Recent human genetic studies have linked a variety of genetic variants in the CACNA1C and CACNA1D genes to neuropsychiatric and neurodevelopmental disorders. This is not surprising given the work from multiple laboratories using cell and animal models that have established that Cav1.2 and Cav1.3 L-type calcium channels (LTCCs), encoded by CACNA1C and CACNA1D, respectively, play a key role in various neuronal processes that are essential for normal brain development, connectivity, and experience-dependent plasticity. Of the multiple genetic aberrations reported, genome-wide association studies (GWASs) have identified multiple single nucleotide polymorphisms (SNPs) in CACNA1C and CACNA1D that are present within introns, in accordance with the growing body of literature establishing that large numbers of SNPs associated with complex diseases, including neuropsychiatric disorders, are present within non-coding regions. How these intronic SNPs affect gene expression has remained a question. Here, we review recent studies that are beginning to shed light on how neuropsychiatric-linked non-coding genetic variants can impact gene expression via regulation at the genomic and chromatin levels. We additionally review recent studies that are uncovering how altered calcium signaling through LTCCs impact some of the neuronal developmental processes, such as neurogenesis, neuron migration, and neuron differentiation. Together, the described changes in genomic regulation and disruptions in neurodevelopment provide possible mechanisms by which genetic variants of LTCC genes contribute to neuropsychiatric and neurodevelopmental disorders.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9980663/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9598433","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions. 卵巢癌症中单羧酸转运蛋白的系统分析及可能的治疗干预措施。

Channels (Austin, Tex.) Pub Date : 2023-12-01 Epub Date: 2023-11-07 DOI: 10.1080/19336950.2023.2273008

Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy

{"title":"A systemic analysis of monocarboxylate transporters in ovarian cancer and possible therapeutic interventions.","authors":"Priti Chatterjee, Debaleena Bhowmik, Sib Sankar Roy","doi":"10.1080/19336950.2023.2273008","DOIUrl":"10.1080/19336950.2023.2273008","url":null,"abstract":"Monocarboxylate transporters (MCTs) play an immense role in metabolically active solid tumors by regulating concentration-dependent transport of different important monocarboxylates including pyruvate and lactate and are encoded by the SLC16A family of genes. Given the vast array of functions, these transporters play in oncogenesis, our objective was to look into the association of MCT1 (SLC16A1), MCT2 (SLC16A7), MCT3 (SLC16A8), and MCT4 (SLC16A3) with Epithelial ovarian cancer (EOC) pathophysiology by exploiting various publicly available databases and web resources. Few of the in silico findings were confirmed via in vitro experiments in EOC cell lines, SKOV3 and OAW-42. MCT1 and MCT4 were found to be upregulated at the mRNA level in OC tissues compared to normal. However, only higher level of MCT4 mRNA was found to be associated with poor patient survival. MCT4 was positively correlated with gene families responsible for invasion, migration, and immune modification, proving it to be one of the most important MCTs for therapeutic intervention. We compared the effects of MCT1/2 blocker SR13800 and a broad-spectrum MCT blocker α-Cyano Hydroxy Cinnamic Acid (α-CHCA) and discovered that α-CHCA has a greater effect on diminishing the invasive behavior of the cancer cells than MCT1/2 blocker SR13800. From our study, MCT4 has emerged as a prospective marker for predicting poor patient outcomes and a potential therapeutic target.","PeriodicalId":72555,"journal":{"name":"Channels (Austin, Tex.)","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2023-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10631444/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0