scholarly journals Analysis of ABC Transporter Gene Expression in Atherosclerosis

2021 ◽  
Vol 11 (4) ◽  
pp. 204-220
Author(s):  
Stanislav Kotlyarov ◽  
Anna Kotlyarova
Keyword(s):  
Gene Expression ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Large Family ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
Transport Mechanisms ◽  
Tissue Samples ◽  
Atherosclerotic Lesions ◽  
Abc Transporter Genes

ABC transporters are a large family of membrane proteins that transport chemically diverse substrates across the cell membrane. Disruption of transport mechanisms mediated by ABC transporters causes the development of various diseases, including atherosclerosis. Methods: A bioinformatic analysis of a dataset from Gene Expression Omnibus (GEO) was performed. A GEO dataset containing data on gene expression levels in samples of atherosclerotic lesions and control arteries without atherosclerotic lesions from carotid, femoral, and infrapopliteal arteries was used for analysis. To evaluate differentially expressed genes, a bioinformatic analysis was performed in comparison groups using the limma package in R (v. 4.0.2) and the GEO2R and Phantasus tools (v. 1.11.0). Results: The obtained data indicate the differential expression of many ABC transporters belonging to different subfamilies. The differential expressions of ABC transporter genes involved in lipid transport, mechanisms of multidrug resistance, and mechanisms of ion exchange are shown. Differences in the expression of transporters in tissue samples from different arteries are established. Conclusions: The expression of ABC transporter genes demonstrates differences in atherosclerotic samples and normal arteries, which may indicate the involvement of transporters in the pathogenesis of atherosclerosis.

Regional variations in ABC transporter expression along the mouse intestinal tract

2004 ◽  
Vol 17 (1) ◽  
pp. 11-20 ◽  
Author(s):  
David M. Mutch ◽  
Pascale Anderle ◽  
Muriel Fiaux ◽  
Robert Mansourian ◽  
Karine Vidal ◽  
...  
Keyword(s):  
Gene Expression ◽  
Abc Transporter ◽  
Expression Profile ◽  
Abc Transporters ◽  
Intestinal Tract ◽  
Expression Profiles ◽  
Expression Patterns ◽  
Assessment Model ◽  
Differentially Expressed ◽  
Distal Intestine

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

scholarly journals Insecticide Exposure Triggers a Modulated Expression of ABC Transporter Genes in Larvae of Anopheles gambiae s.s.

Insects ◽  
2019 ◽  
Vol 10 (3) ◽  
pp. 66 ◽  
Author(s):  
Valentina Mastrantonio ◽  
Marco Ferrari ◽  
Agata Negri ◽  
Tommaso Sturmo ◽  
Guido Favia ◽  
...  
Keyword(s):  
Anopheles Gambiae ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Larval Mortality ◽  
Expression Patterns ◽  
Main Tool ◽  
Gene Expression Response ◽  
Abc Transporter Genes

Insecticides remain a main tool for the control of arthropod vectors. The urgency to prevent the insurgence of insecticide resistance and the perspective to find new target sites, for the development of novel molecules, are fuelling the study of the molecular mechanisms involved in insect defence against xenobiotic compounds. In this study, we have investigated if ATP-binding cassette (ABC) transporters, a major component of the defensome machinery, are involved in defence against the insecticide permethrin, in susceptible larvae of the malaria vector Anopheles gambiae sensu stricto. Bioassays were performed with permethrin alone, or in combination with an ABC transporter inhibitor. Then we have investigated the expression profiles of five ABC transporter genes at different time points following permethrin exposure, to assess their expression patterns across time. The inhibition of ABC transporters increased the larval mortality by about 15-fold. Likewise, three genes were up-regulated after exposure to permethrin, showing different patterns of expression across the 48 h. Our results provide the first evidences of ABC transporters involvement in defence against a toxic in larvae of An. gambiae s.s. and show that the gene expression response is modulated across time, being continuous, but stronger at the earliest and latest times after exposure.

ABCChips as New Diagnostic Tool to Monitoring Multidrug Resistance in Human Tumor Cells to Chemotherapeutics Agents by Expression Profiling of ATP-Binding Cassette Transporter Genes.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4360-4360
Author(s):  
Jean-Pierre Gillet ◽  
Thomas Efferth ◽  
Damiel Steinbach ◽  
Françoise de Longueville ◽  
Vincent Bertholet ◽  
...  
Keyword(s):  
Cell Lines ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Diagnostic Tool ◽  
Human Tumor ◽  
Multidrug Resistant ◽  
Parental Cell ◽  
Hybridization Experiment ◽  
Low Density ◽  
Abc Transporter Genes

Abstract A major problem in the treatment of tumors represents the development of resistance to chemotherapy. Many mechanisms are responsible for the failure of treatment, the main one being the activation of the ABC transporters. In the present investigation, we developed a low density DNA microarray which contains 38 ABC transporter genes. This tool has been validated with three different characterized multidrug-resistant sublines (CEM/ADR5000, HL60/AR, MCF7-CH1000) and their corresponding drug-sensitive parental cell lines (CCRF-CEM, HL60, MCF7). The multidrug-resistant cell lines used are known to overexpress either the MDR1, MRP1, or BCRP genes. Interestingly, we found not only the overexpression of these genes but also of other ABC transporter genes by using low density microarrays. These results were corroborated by quantitative real time RT-PCR. The microarray allowed the determination of the expression profile of ABC transporters in a single hybridization experiment and may, hence harbor the potential as diagnostic tool to detect drug resistance in the clinic.

scholarly journals ATP-Binding Cassette (ABC) Transporter Genes Involved in Pyrethroid Resistance in the Malaria Vector Anopheles sinensis: Genome-Wide Identification, Characteristics, Phylogenetics, and Expression Profile

2019 ◽  
Vol 20 (6) ◽  
pp. 1409 ◽  
Author(s):  
Qiyi He ◽  
Zhentian Yan ◽  
Fengling Si ◽  
Yong Zhou ◽  
Wenbo Fu ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Pyrethroid Resistance ◽  
Expression Profiles ◽  
Anopheles Sinensis ◽  
Atp Binding ◽  
Rna Seq ◽  
Transporter Family ◽  
Abc Transporter Genes ◽  
Atp Binding Cassette

background: The ATP-binding cassette (ABC) transporters family is one of the largest families of membrane proteins existing in all living organisms. Pyrethroid resistance has become the largest unique obstacle for mosquito control worldwide. ABC transporters are thought to be associated with pyrethroid resistance in some agricultural pests, but little information is known for mosquitoes. Herein, we investigated the diversity, location, characteristics, phylogenetics, and evolution of ABC transporter family of genes in the Anopheles sinensis genome, and identified the ABC transporter genes associated with pyrethroid resistance through expression profiles using RNA-seq and qPCR. Results: 61 ABC transporter genes are identified and divided into eight subfamilies (ABCA-H), located on 22 different scaffolds. Phylogenetic and evolution analyses with ABC transporters of A. gambiae, Drosophila melanogaster, and Homo sapiens suggest that the ABCD, ABCG, and ABCH subfamilies are monophyly, and that the ABCC and ABCG subfamilies have experienced a gene duplication event. Both RNA-seq and qPCR analyses show that the AsABCG28 gene is uniquely significantly upregulated gene in all three field pyrethroid-resistant populations (Anhui, Chongqing, and Yunnan provinces) in comparison with a laboratory-susceptible strain from Jiangsu province. The AsABCG28 is significantly upregulated at 12-h and 24-h after deltamethrin exposure in three-day-old female adults. Conclusion: This study provides the information frame for ABC transporter subfamily of genes, and lays an important basis for the better understanding and further research of ABC transporter function in insecticide toxification. The AsABCG28 gene is associated with pyrethroid detoxification, and it functions at later period in the detoxification process for xenobiotics transportation.

scholarly journals Genome-Wide Identification and Characterization of ABC Transporters in Nine Rosaceae Species Identifying MdABCG28 as a Possible Cytokinin Transporter linked to Dwarfing

2019 ◽  
Vol 20 (22) ◽  
pp. 5783
Author(s):  
Yi Feng ◽  
Qiran Sun ◽  
Guifen Zhang ◽  
Ting Wu ◽  
Xinzhong Zhang ◽  
...  
Keyword(s):  
Abc Transporter ◽  
Abc Transporters ◽  
Prunus Persica ◽  
Prunus Avium ◽  
Structural Features ◽  
Apple Rootstocks ◽  
Specific Expression ◽  
Protein Motifs ◽  
Rosaceae Species ◽  
Abc Transporter Genes

ATP-binding cassette (ABC) transporters constitute a large, diverse, and ubiquitous superfamily that is involved in a broad range of processes. The completion of genome sequencing provides an opportunity to understand the phylogenetic history of the ABC transporter superfamily among Rosaceae species. This study identified a total of 1323 ABC transporter genes from nine Rosaceae genomes: 191 from Malus domestica, 174 from Pyrus communis, 138 from Prunus persica, 118 from Prunus avium, 141 from Prunus dulcis, 122 from Fragaria vesca, 98 from Rubus occidentalis, 162 from Prunus mume, and 179 from Rosa chinensis. Their chemical characterization, phylogenetic analysis, chromosomal localization, gene structure, gene duplication, and tissue-specific expression were studied. Their subcellular localization, transmembrane structures, and protein motifs were predicted. All the ABC transporter genes were grouped into eight subfamilies on the basis of their phylogenetic relationships and structural features. Furthermore, cis-element and expression analysis of 10 potential phytohormone transporters in MdABCG subfamily genes were also performed. Loss of the W-box in the promoter region of MdABCG28 was found to reduce the gene expression level and was linked to the dwarfing phenotype in apple rootstocks. MdABCG28 overexpression promoted shoot growth of atabcg14 mutants in Arabidopsis.

Selective Expression of a Number of ABC Transporter Genes in Normal CD34+CD38− Versus CD34+CD38− Cells, with a Reverse Pattern in a Subgroup of AML Patients.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 4291-4291
Author(s):  
Dorina M. van der Kolk ◽  
Susan D.P.W.M. Peeters ◽  
Gerald de Haan ◽  
Leonid Bystrykh ◽  
Elisabeth G.E. de Vries ◽  
...  
Keyword(s):  
Stem Cells ◽  
Hematopoietic Stem Cells ◽  
Mrna Expression ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Cholesterol Synthesis ◽  
Leukemic Stem Cells ◽  
Hematopoietic Stem ◽  
Reverse Pattern ◽  
Abc Transporter Genes

Abstract Several ABC transporters involved in drug transport have been identified in hematopoietic stem cells, including ABCB1, ABCC1 and ABCG2. The ABC transporters play a role in chemotherapy resistant AML, although the relevant information is mostly obtained from the total AML cell population instead of the leukemic stem cells characterized by the CD34+CD38− phenotype. In this study we investigated which ABC transporters are selectively expressed in normal CD34+CD38− hematopoietic stem cells versus CD34+CD38+ cells, and to what extent lineage-restricted modulation is aberrantly regulated in AML stem cells. We first investigated murine microarray expression data of 29 ABC transporter genes in lin−sca-1+c-kit+ cells (available on www.webqtl.org). Based on these data 7 of the 29 ABC transporters were selected with a high expression profile (abcg1, abcb2, abca2, abcd1, abcc3, abcc5, and abcg2). Based on data published at www.sciencemag.org/cgi/content/full/1073823/DC1, concerning the lineage restricted expression of genes in lin−AA4.1+ + c-kit+sca-1+ murine stem cells, 6 additional stem cell-related ABC transporters (abcb1, abcb11, abcc1b, abcd4, abce1 and abcf2) were selected. The mRNA expression of the 13 ABC transporters was analyzed in the CD34+CD38− versus CD34+CD38+ fraction of human normal bone marrow cells (n=10) by quantitative RT-PCR. Five ABC transporter genes were not detectable in the human CD34+CD38− and CD34+CD38+cells (ABCA2, ABCB11, ABCC3, ABCD1 and ABCF2). Three ABC transporters were expressed equally in both fractions (ABCC5, ABCE1 and ABCG2). However, five ABC transporters were differentially expressed, with a higher expression in the CD34+CD38− cells, (ABCB1, ratio of CD34+CD38+/CD34+CD38− expression of 0.22, p<0.001; ABCG1, 0.27, p<0.001; ABCC1, 0.52, p<0.001; ABCD4, 0.60, p<0.001; and ABCB2, 0.71, p<0.02). Additionally these five ABC transporters were studied in sorted AML subpopulations (n=7). In the sorted AML cells (CD34+CD38− versus CD34+CD38+) a more heterogeneous expression pattern was observed as compared to normal CD34+CD38− cells. In general, the expression levels of ABCB1 and ABCC1 in the AML subpopulations were lower than in normal CD34+CD38− cells, ABCB2 expression was higher in the AML fractions and ABCG1 and ABCD4 were expressed similar in AML and normal CD34+CD38− cells. Downregulation of the ABC transporters in the leukemic CD34+CD38+ cells was observed in 50%–60% of the samples, the reverse pattern was observed for the remaining cases, independent of FAB classification. Since ABCG1 plays a prominent role in cholesterol transport and was strongly downregulated in normal CD34+CD38+ cells (ratio 0.27, p<0.001), the mRNA expression of a number of additional cholesterol synthesis genes was investigated. PPARβ, LXRα and HMCGCoA reductase appeared to be downregulated in the CD34+CD38+ cells (ratios of 0.59, p=0.002, 0.32, p<0.001 and 0.59, p= 0.002 respectively). In conclusion, these results indicate that cholesterol synthesis and transport might play an important role in hematopoietic stem cells. Furthermore, a number of ABC transporter genes appeared to be predominantly expressed in hematopoietic stem cells, and are downregulated upon maturation, whereas the reverse pattern is observed in about 40% of the AML patients suggesting that these more committed leukemic cells might have gained some properties of the leukemic stem cells.

scholarly journals Identification of ARHGEF38, NETO2, GOLM1, and SAPCD2 Associated With Prostate Cancer Progression by Bioinformatic Analysis and Experimental Validation

2021 ◽  
Vol 9 ◽  
Author(s):  
Zhuolun Sun ◽  
Yunhua Mao ◽  
Xu Zhang ◽  
Shuo Lu ◽  
Hua Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Prostate Cancer ◽  
Cancer Progression ◽  
Cox Regression ◽  
Prognostic Indicator ◽  
Bioinformatic Analysis ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Prognostic Signature ◽  
Tcga Dataset

Prostate cancer (PCa) represents one of the most prevalent types of cancers and is a large health burden for men. The pathogenic mechanisms of PCa still need further investigation. The aim of this study was to construct an effective signature to predict the prognosis of PCa patients and identify the biofunctions of signature-related genes. First, we screened differentially expressed genes (DEGs) between PCa and normal control tissues in The Cancer Genome Atlas (TCGA) and GSE46602 datasets, and we performed weighted gene co-expression network analysis (WGCNA) to determine gene modules correlated with tumors. In total, 124 differentially co-expressed genes were retained. Additionally, five genes (ARHGEF38, NETO2, PRSS21, GOLM1, and SAPCD2) were identified to develop the prognostic signature based on TCGA dataset. The five-gene risk score was verified as an independent prognostic indicator through multivariate Cox regression analyses. The expression of the five genes involved in the signature was detected in the Gene Expression Omnibus (GEO), Gene Expression Profiling Interactive Analysis (GEPIA), and Oncomine databases. In addition, we utilized DiseaseMeth 2.0 and MEXPRESS for further analysis and found that abnormal methylation patterns may be a potential mechanism for these five DEGs in PCa. Finally, we observed that these genes, except PRSS21, were highly expressed in tumor samples and PCa cells. Functional experiments revealed that silencing ARHGEF38, NETO2, GOLM1, and SAPCD2 suppressed the proliferation, migration, and invasiveness of PCa cells. In summary, this prognostic signature had significant clinical significance for treatment planning and prognostic evaluation of patients with PCa. Thus, ARHGEF38, NETO2, GOLM1, and SAPCD2 may serve as oncogenes in PCa.

scholarly journals Identification of Novel Hub Genes Associated With Gastric Cancer Using Integrated Bioinformatics Analysis

2020 ◽  
Author(s):  
Xiao-Qing Lu ◽  
Jia-qian Zhang ◽  
Jun Qiao ◽  
Sheng-Xiao Zhang ◽  
Meng-Ting Qiu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Malignant Tumors ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Expression Omnibus ◽  
High Recurrence Rate ◽  
Hub Genes ◽  
Tissue Samples ◽  
Qrt Pcr

Abstract Background: Gastric cancer (GC) is one of the most common solid malignant tumors worldwide with a high-recurrence-rate. Identifying the molecular signatures and specific biomarkers of GC might provide novel clues for GC prognosis and targeted therapy.Methods: Gene expression profiles were obtained from the ArrayExpress and Gene Expression Omnibus database. Differentially expressed genes (DEGs) were picked out by R software. The hub genes were screened by cytoHubba plugin. Their prognostic values were assessed by Kaplan–Meier survival analyses and the gene expression profiling interactive analysis (GEPIA). Finally, qRT-PCR in GC tissue samples was established to validate these DEGs. Results: Total of 295 DEGs were identified between GC and their corresponding normal adjacent tissue samples in E-MTAB-1440, GSE79973, GSE19826, GSE13911, GSE27342, GSE33335 and GSE56807 datasets, including 117 up-regulated and 178 down-regulated genes. Among them, 7 vital upregulated genes (HMMR, SPP1, FN1, CCNB1, CXCL8, MAD2L1 and CCNA2) were selected. Most of them had a significantly worse prognosis except SPP1. Using qRT-PCR, we validated that their transcriptions in our GC tumor tissue were upregulated except SPP1 and FN1, which correlated with tumor relapse and predicts poorer prognosis in GC patients.Discussion: We have identified 5 upregulated DEGs (HMMR, CCNB1, CXCL8, MAD2L1, and CCNA2) in GC patients with poor prognosis using integrated bioinformatical methods, which could be potential biomarkers and therapeutic targets for GC treatment.

Role of ABC transporters in the pathology of Alzheimer’s disease

2017 ◽  
Vol 28 (2) ◽  
pp. 155-159 ◽  
Author(s):  
Yan Zhao ◽  
Deren Hou ◽  
Xialu Feng ◽  
Fangbo Lin ◽  
Jing Luo
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Present Article ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Cholesterol Metabolism ◽  
Current Knowledge ◽  
Large Family ◽  
Cholesterol Homeostasis

AbstractThe ATP-binding cassette (ABC) transporter superfamily is a large family of proteins that transport specific molecules across membranes. These proteins are associated with both cholesterol metabolism and Alzheimer’s disease (AD). Cholesterol homeostasis has a key role in AD, and ABC transporters are important mediators of lipid transportation. Emerging evidence suggests that decreased expression and hypofunction of ABC transporters are crucial to the occurrence and development of AD. In the present article, we review the current knowledge regarding ABC transporters and speculate on their role in the pathogenesis of AD.

scholarly journals Purification, crystallization and preliminary X-ray diffraction studies of the ATP-binding subunit of an ABC transporter fromGeobacillus kaustophilus

2012 ◽  
Vol 68 (11) ◽  
pp. 1406-1408
Author(s):  
Mallappa Manjula ◽  
Kudigana J. Pampa ◽  
Shankar Madan Kumar ◽  
Naoki Kunishima ◽  
Neratur K. Lokanath
Keyword(s):  
Lipid Bilayers ◽  
Abc Transporter ◽  
Abc Transporters ◽  
Large Family ◽  
Atp Binding ◽  
X Ray Diffraction ◽  
Orthorhombic Space Group ◽  
X Ray ◽  
Cell Parameters ◽  
Binding Subunit

ATP-binding cassette (ABC) transporters, also known as traffic ATPases, form a large family of integral membrane proteins responsible for the translocation of a variety of chemically diverse substrates across the lipid bilayers of cellular membranes of both prokaryotes and eukaryotes by the hydrolysis of ATP. The ATP-binding subunit of an ABC transporter fromGeobacillus kaustophilus, a homodimeric enzyme, was overexpressed inEscherichia coliand purified. Crystals were obtained using the microbatch-under-oil method at 291 K. X-ray diffraction data to 1.6 Å resolution were collected on SPring-8 beamline BL26B1. The crystals belonged to the orthorhombic space groupI222, with unit-cell parametersa= 54.94,b = 78.63,c= 112.96 Å. Assuming the presence of a dimer in the asymmetric unit gave a crystal volume per protein weight (VM) of 2.32 Å3 Da−1and a solvent content of 47%; this was consistent with the results of a dynamic light-scattering experiment, which showed a dimeric state of the protein in solution. Molecular-replacement trials using the crystal structure of HisP from theSalmonella typhimuriumATP-binding subunit of an ABC transporter as a search model did not provide a satisfactory solution, indicating that the two ATP-binding subunits of ABC transporters have substantially different structures.

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