The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes

Schnell, Christian; Shahmoradi, Ali; Wichert, Sven P.; Mayerl, Steffen; Hagos, Yohannes; Heuer, Heike; Rossner, Moritz J.; Hülsmann, Swen

doi:10.1007/s00429-013-0645-0

Cited by 73 publications

(69 citation statements)

References 38 publications

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“…Note that hybridization signal labels vessel segments in the control, but not in LPS-injected brain. Scale bar ϭ 50 m. OATP1c1 mRNA in astrocytes varied greatly between brain regions, confirming recent studies (23,27). In mice, OATP1c1 mRNA was easily detected in hippocampal and cortical astrocytes, whereas it was not detected in hypothalamic astrocytes with the exposure time used in this experiment.…”

Section: Oatp1c1 Mrnasupporting

confidence: 90%

“…Of the several proteins capable of TH transport and present in the rodent brain (22,23), we focused on OATP1c1 and MCT8 because they are critically important for brain TH homeostasis (24). Both transporters facilitate TH traffic in multiple cell types (25)(26)(27)(28)(29)(30) and are indispensable for TH entry into the brain via the blood-brain and/or blood-cerebrospinal fluid barrier (24,(31)(32)(33)(34). In fact, almost the entire T 3 uptake into the brain is facilitated by MCT8 (32), whereas both MCT8 and OATP1c1 contribute to T 4 uptake (24).…”

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confidence: 99%

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Parallel Regulation of Thyroid Hormone Transporters OATP1c1 and MCT8 During and After Endotoxemia at the Blood-Brain Barrier of Male Rodents

et al. 2015

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There is increasing evidence that local thyroid hormone (TH) availability changes profoundly in inflammatory conditions due to altered expression of deiodinases that metabolize TH. It is largely unknown, however, how inflammation affects TH availability via the expression of TH transporters. In this study we examined the effect of bacterial lipopolysaccharide (LPS) administration on two TH transporters that are critically important for brain TH homeostasis, organic anion-transporting polypeptide 1c1 (OATP1c1), and monocarboxylate transporter 8 (MCT8). MRNA levels were studied by in situ hybridization and qPCR as well as protein levels by immunofluorescence in both the rat and mouse forebrain. The mRNA of both transporters decreased robustly in the first 9 hours after LPS injection, specifically in brain blood vessels; OATP1c1 mRNA in astrocytes and MCT8 mRNA in neurons remained unchanged. At 24 and/or 48 hours after LPS administration, OATP1c1 and MCT8 mRNAs increased markedly above control levels in brain vessels. OATP1c1 protein decreased markedly in vessels by 24 hours whereas MCT8 protein levels did not decrease significantly. These changes were highly similar in mice and rats. The data demonstrate that OATP1c1 and MCT8 expression are regulated in a parallel manner during inflammation at the blood-brain barrier of rodents. Given the indispensable role of both transporters in allowing TH access to the brain, the results suggest reduced brain TH uptake during systemic inflammation.

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Section: Oatp1c1 Mrnasupporting

confidence: 90%

mentioning

confidence: 99%

Parallel Regulation of Thyroid Hormone Transporters OATP1c1 and MCT8 During and After Endotoxemia at the Blood-Brain Barrier of Male Rodents

et al. 2015

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“…56) However, Hülsmann's group has recently clarified that SR101-labelling intensity is severely reduced in the presence of rifampicin and dehydroepiandrosterone sulfate, which are OATP substrates/inhibitors, 57) and SR101-labelled astrocytes mostly disappeared in Oatp1c1-knockout mice. 58) OATP1C1 is a multi-specific organic anion transporter, but its primary substrates are thyroid hormones, with the highest activity towards 3,5,3′,5′-tetraiodothyronine (thyroxine, T4). 59,60) The thyroid hormone transporting ability of OATP1C1 is in good agreement with the critical roles of astrocytes in CNS thyroid hormone homeostasis.…”

Section: Organic Anion Transportersmentioning

confidence: 99%

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Furihata

Anzai

2017

Biological & Pharmaceutical Bulletin

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It has become widely acknowledged that astrocytes play essential roles in maintaining physiological central nervous system (CNS) activities. Astrocytes fulfill their roles partly through the manipulation of their plasma membrane transporter functions, and therefore these transporters have been regarded as promising drug targets for various CNS diseases. A representative example is excitatory amino acid transporter 2 (EAAT2), which works as a critical regulator of excitatory signal transduction through its glutamate uptake activity at the tripartite synapse. Thus, enhancement of EAAT2 functionality is expected to accelerate glutamate clearance at synapses, which is a promising approach for the prevention of over-excitation of glutamate receptors. In addition to such well-known astrocyte-specific transporters, cumulative evidence suggests that multi-specific organic ion transporters (i.e., organic cation/anion transporters [OCTs/OATs], carnitine/organic cation transporters [OCTNs], and organic anion transporting polypeptides [OATPs]) are also functionally expressed in astrocytes. Even though identification and characterization of their physiological/pathophysiological roles in astrocytes are in the initial stage, the findings obtained so far indicate that OCT3 and plasma membrane monoamine transporter are significantly involved in the clearance of biogenic amine neurotransmitters in the synaptic cleft, and that OCTN2 and OATP1C1 provide a cellular entry gate for carnitine/acetyl-L-carnitine and thyroxine, respectively. Therefore, organic ion transporters, including those mentioned above, are expected to become emerging pharmacological targets for various CNS diseases. With such expectations in mind, this review will briefly summarize the functional expression of organic ion transporters in astrocytes.

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“…As a first step toward the characterization of region-specific molecular signatures of astrocytes, we have combined FACS with 3' digital gene expression [20]. In this RNAseq approach, we selectively focused on mRNAs expression profiles of astrocytes FACS isolated from the cortex (Cx), hippocampus (Hi), and brainstem (Bs).…”

Section: Transcriptomic Approaches To Unravel Glial Heterogeneitymentioning

confidence: 99%

“…Fig. 1a-d) [20]. This study was purely hypothesis driven and utilized only a small fraction of the obtained data.…”

Section: Transcriptomic Approaches To Unravel Glial Heterogeneitymentioning

confidence: 99%

Dissecting the regional diversity of glial cells by applying -omic technologies

Dieterich

Rossner²

2015

E-Neuroforum

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With an estimated number of approximately 10,000 different proteins in each single mammalian cell [16], in-depth identification of a cell's entire proteome Dissecting the regional diversity of glial cells by applying -omic technologies Abstract Neuronal as well as glial cells contribute to higher order brain functions. Many observations show that neurons and glial cells are not only physically highly intermingled but are physiologically tightly connected and mutually depend at various levels on each other. Moreover, macroglia classes like astrocytes, NG2 cells and oligodendrocytes are not at all homogenous cell populations but do possess a markedly heterogeneity in various aspects similar to neurons. The diversity of differences in morphology, functionality and, cellular activity has been acknowledged recently and will be integrated into a concept of brain function that pictures a neural rather than a puristical neuronal world. With the recent progress in "omic" technologies, an unbiased and exploratory approach toward an enhanced understanding of glial heterogeneity has become possible. Here, we provide an overview on current technical transcriptomic and proteomic approaches used to dissect glial heterogeneity of the brain. is still a major challenge for modern proteomic technologies. In addition, the total number of different/unique proteins per synapse is estimated to be at approximately 2000-2500 [17], which are often under control of different activity-dependent turnover rates. While today's state-of-theart MS instruments routinely sequence single purified proteins with subfemtomolar sensitivity, the effective identification of low-abundance proteins is orders of magnitude lower in complex mixtures due to limited dynamic range and sequencing speed and due to the common, strong bias toward acquiring MS/MS data on higher abundance molecules. Hence, to tackle activity-dependent proteome alterations entire, functionally heterogeneous brain regions with different subtypes of neurons and macroglial cells are usually being sampled at the loss of cell-type specificity and spatial resolution. The characterization of a proteome is an even more difficult challenge if temporal and spatial aspects of a proteome or a subpopulation of the proteome have to be taken into consideration. Thus, the separation and enrichment of the subproteome in question is key for its successful characterization. To overcome the above mentioned limitations, several cellular and biochemical (subcellular) enrichment strategies combined with proteomics have been developed to increase sensitivity and selectivity for the analysis of neuronal and glial proteomes, and to finally dissolve cellular heterogeneity of neural cells in the brain (. Fig. 2a-b). KeywordsConcerning cellular selectivity, intracellular proteomes and secretomes from cultured primary astrocytes and astroglial cell lines have been characterized in detail by several labs as proteomic approaches as indicated above require a much larger quantity than transcriptomic approaches. Analys...

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The multispecific thyroid hormone transporter OATP1C1 mediates cell-specific sulforhodamine 101-labeling of hippocampal astrocytes

Cited by 73 publications

References 38 publications

Parallel Regulation of Thyroid Hormone Transporters OATP1c1 and MCT8 During and After Endotoxemia at the Blood-Brain Barrier of Male Rodents

Parallel Regulation of Thyroid Hormone Transporters OATP1c1 and MCT8 During and After Endotoxemia at the Blood-Brain Barrier of Male Rodents

Functional Expression of Organic Ion Transporters in Astrocytes and Their Potential as a Drug Target in the Treatment of Central Nervous System Diseases

Dissecting the regional diversity of glial cells by applying -omic technologies

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