79. LXR and ABC-transporter-expression patterns in the placenta in IUGR

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.

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EAAT2 Expression in the Hippocampus, Subiculum, Entorhinal Cortex and Superior Temporal Gyrus in Alzheimer’s Disease

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.702824 ◽

2021 ◽

Vol 15 ◽

Author(s):

Jason H. Y. Yeung ◽

Thulani H. Palpagama ◽

Oliver W. G. Wood ◽

Clinton Turner ◽

Henry J. Waldvogel ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Entorhinal Cortex ◽

Excitatory Amino Acid ◽

Glutamate Uptake ◽

Expression Patterns ◽

Superior Temporal Gyrus ◽

Altered Expression ◽

And Control ◽

Transporter Expression

Alzheimer’s disease (AD) is a neuropathological disorder characterized by the presence and accumulation of amyloid-beta plaques and neurofibrillary tangles. Glutamate dysregulation and the concept of glutamatergic excitotoxicity have been frequently described in the pathogenesis of a variety of neurodegenerative disorders and are postulated to play a major role in the progression of AD. In particular, alterations in homeostatic mechanisms, such as glutamate uptake, have been implicated in AD. An association with excitatory amino acid transporter 2 (EAAT2), the main glutamate uptake transporter, dysfunction has also been described. Several animal and few human studies examined EAAT2 expression in multiple brain regions in AD but studies of the hippocampus, the most severely affected brain region, are scarce. Therefore, this study aims to assess alterations in the expression of EAAT2 qualitatively and quantitatively through DAB immunohistochemistry (IHC) and immunofluorescence within the hippocampus, subiculum, entorhinal cortex, and superior temporal gyrus (STG) regions, between human AD and control cases. Although no significant EAAT2 density changes were observed between control and AD cases, there appeared to be increased transporter expression most likely localized to fine astrocytic branches in the neuropil as seen on both DAB IHC and immunofluorescence. Therefore, individual astrocytes are not outlined by EAAT2 staining and are not easily recognizable in the CA1–3 and dentate gyrus regions of AD cases, but the altered expression patterns observed between AD and control hippocampal cases could indicate alterations in glutamate recycling and potentially disturbed glutamatergic homeostasis. In conclusion, no significant EAAT2 density changes were found between control and AD cases, but the observed spatial differences in transporter expression and their functional significance will have to be further explored.

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ABC transporters in gills of rainbow trout (Oncorhynchus mykiss)

Journal of Experimental Biology ◽

10.1242/jeb.221069 ◽

2020 ◽

Vol 223 (15) ◽

pp. jeb221069

Author(s):

Christian Kropf ◽

Karl Fent ◽

Stephan Fischer ◽

Ayako Casanova ◽

Helmut Segner

Keyword(s):

Rainbow Trout ◽

Abc Transporter ◽

Abc Transporters ◽

Functional Activity ◽

Organic Molecules ◽

Expression Patterns ◽

Primary Cultures ◽

Gene Transcript ◽

Rainbow Trout Oncorhynchus Mykiss

ABSTRACTFish gills are a structurally and functionally complex organ at the interface between the organism and the aquatic environment. Gill functions include the transfer of organic molecules, both natural ones and xenobiotic compounds. Whether the branchial exchange of organic molecules involves active transporters is currently not known. Here, we investigated the presence, diversity and functional activity of ATP-binding cassette (ABC) transporters in gills of juvenile rainbow trout. By means of RT-qPCR, gene transcripts of members from the abcb, abcc and abcg subfamilies were identified. Comparisons with mRNA profiles from trout liver and kidney revealed that ABC transporters known to have an apical localization in polarized epithelia, especially abcc2 and abcb1, were under-represented in the gills. In contrast, ABC transporters with mainly basolateral localization showed comparable gene transcript levels in the three organs. The most prominent ABC transporter in gills was an abcb subfamily member, which was annotated as abcb5 based on the synteny and phylogeny. Functional in vivo assays pointed to a role of branchial ABC transporters in branchial solute exchange. We further assessed the utility of primary gill cell cultures to characterize transporter-mediated branchial exchange of organic molecules, by examining ABC transporter gene transcript patterns and functional activity in primary cultures. The gill cultures displayed functional transport activity, but the ABC mRNA expression patterns were different to those of the intact gills. Overall, the findings of this study provide evidence for the presence of functional ABC transporter activity in gills of fish.

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

Insects ◽

10.3390/insects10030066 ◽

2019 ◽

Vol 10 (3) ◽

pp. 66 ◽

Cited By ~ 6

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.

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Guajadial reverses multidrug resistance by inhibiting ABC transporter expression and suppressing the PI3K/Akt pathway in drug-resistant breast cancer cells

Chemico-Biological Interactions ◽

10.1016/j.cbi.2019.03.032 ◽

2019 ◽

Vol 305 ◽

pp. 98-104 ◽

Cited By ~ 4

Author(s):

Yaxun Li ◽

Zhenhua Zhai ◽

Hao Li ◽

Xudong Wang ◽

Yinpeng Huang ◽

...

Keyword(s):

Breast Cancer ◽

Multidrug Resistance ◽

Cancer Cells ◽

Abc Transporter ◽

Breast Cancer Cells ◽

Akt Pathway ◽

Drug Resistant ◽

Transporter Expression

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Human ATP-Binding Cassette Transporter TaqMan Low-Density Array: Analysis of Macrophage Differentiation and Foam Cell Formation

Clinical Chemistry ◽

10.1373/clinchem.2005.059774 ◽

2006 ◽

Vol 52 (2) ◽

pp. 310-313 ◽

Cited By ~ 39

Author(s):

Thomas Langmann ◽

Richard Mauerer ◽

Gerd Schmitz

Keyword(s):

Multidrug Resistance ◽

Abc Transporter ◽

Abc Transporters ◽

Metabolic Regulation ◽

Foam Cell ◽

Expression Patterns ◽

Foam Cell Formation ◽

Atp Binding ◽

Low Density ◽

Atp Binding Cassette

Abstract Background: ATP-binding cassette (ABC) transporters cause various diseases and regulate many physiologic processes, such as lipid homeostasis, iron transport, and immune mechanisms. Several ABC transporters are involved in bile acid, phospholipid, and sterol transport, and their expression is itself controlled by lipids. In addition, ABC proteins mediate drug export in tumor cells and promote the development of multidrug resistance. Methods: We created an ABC Transporter TaqMan Low-Density Array based on an Applied Biosystems 7900HT Micro Fluidic Card. We used a 2-μL reaction well with 2 ng of sample. To evaluate this method for lipidomic research and to characterize expression patterns of ABC transporters in cells relevant for atherosclerosis research, we monitored mRNA expression in human primary monocytes, in vitro–differentiated macrophages, and cells stimulated with the liver-X-receptor and retinoid-X-receptor agonists T0901317 and 9-cis retinoic acid, mimicking sterol loading. Results: The method enabled simultaneous analysis of 47 human ABC transporters and the reference gene 18S rRNA in 2 replicates of 4 samples per run. Conclusions: The new system uses only 2 ng of sample and small volumes of reagent, and the precaptured primers and probes avoided labor-intensive pipetting steps. The ABC Transporter TaqMan Low-Density Array may be a useful tool to monitor dysregulated ABC transporter mRNA profiles in human lipid disorders and cancer-related multidrug resistance and to analyze the pharmacologic and metabolic regulation of ABC transporter expression important for drug development in large-scale screening approaches.

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