Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain

Tomioka, Nobuo; Tamura, Yoshifuru; Takada, Tappei; Shibata, Shigeru; Suzuki, Hiroshi; Uchida, Shunya; Hosoyamada, Makoto

doi:10.1186/s12987-016-0046-x

Cited by 14 publications

(28 citation statements)

References 48 publications

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“…Recent reports have indicated that ependymal cells, which separate the CSF from brain parenchyma, express several transporters, such as L-glutamate transporters 33) and urate transporters. 34) In addition to these reports, Yasuda et al have found that arachnoid barrier epithelial cells, which are present in meninges, express several kinds of transporters, such as P-glycoprotein and ATPbinding cassette transporter G2. 35) Thus, there is a possibility that these epithelial cells also involves in vivo spermine elimination from the CSF.…”

Section: Resultsmentioning

confidence: 96%

Involvement of Carrier-Mediated Transport at the Blood–Cerebrospinal Fluid Barrier in Spermine Clearance from Rat Brain

Akanuma

Shimada

Kubo

et al. 2017

Biological & Pharmaceutical Bulletin

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Spermine is the end-product in the polyamine biosynthetic pathway, and its excess accumulation induces neuroexcitatory responses and neurotoxicity. The purpose of this study was to elucidate the involvement of transport systems at the brain barriers in the clearance of spermine. In vivo rat spermine elimination from brain parenchyma across the blood-brain barrier (BBB) and blood-cerebrospinal fluid (CSF) barrier (BCSFB) was assessed by intracerebral and intracerebroventricular administration techniques, respectively. To characterize spermine transport at the BCSFB, a transport study using rat choroid plexus was performed. After the intracerebral microinjection of [ Spermine is a natural polyamine, and the end-product in the polyamine biosynthetic pathway.1) In the brain, spermine binds to N-methyl-D-aspartate receptors, and is involved in the modulation of learning and memory.2,3) In addition, excess accumulation of spermine induces neuroexcitatory responses and, thus, neurotoxicity. 4) Therefore, it is considered that some mechanisms for control of the cerebral spermine concentration are present in the brain to maintain homeostasis of cerebral function via spermine-related neuro-responses. The precursor of spermine is spermidine, 5) which is synthesized from putrescine and it has been reported that the biosynthesis of spermine from spermidine is superior to that of spermidine from spermine.6-8) Hence, neural spermine transport system(s) could be important for the removal of spermine from the brain, and the modulation of cerebral spermine concentration.Brain parenchyma and cerebrospinal fluid (CSF) are separated from the circulating blood by the blood-brain barrier (BBB) and blood-CSF barrier (BCSFB), respectively. The BBB and BCSFB are formed by brain capillary endothelial and choroid plexus epithelial cells, respectively, and express some transporting molecules which are involved in active elimination of compound from the brain or CSF.9) Regarding the cationic compound elimination system(s) at these barriers, mRNAs of plasma membrane monoamine transporter (PMAT/ solute carrier (SLC)29A4), organic cation/carnitine transporter 1-2 (OCTN1-2/SLC22A4-5), organic cation transporter 1-3 (OCT1-3/SLC22A1-3), and multidrug and toxin extrusion 1-2 (MATE1-2/SLC47A1-2) are expressed in rat BBB and BCSFB cell lines. 10) Among these transporters, PMAT is, at least in part, involved in brain/CSF-to-blood transport of 1-methyl-4-phenylpyridinium (MPP + ) 10) and CSF-to-blood transport of histamine.11) In addition, OCT3 takes part in the efflux transport of creatinine, a cationic guanidino compound.12) Therefore, it is possible that cerebral spermine is eliminated across these brain barriers.Some previous studies have reported that polyamines including spermine are transported in a carrier-mediated manner in some organs and it has been reported that carrier-mediated transport of polyamines is present in mammalian intestine, liver, and kidney. [13][14][15] In addition, we have demonstrated that the rat inner blood-retinal barr...

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Section: Resultsmentioning

confidence: 96%

Involvement of Carrier-Mediated Transport at the Blood–Cerebrospinal Fluid Barrier in Spermine Clearance from Rat Brain

Akanuma

Shimada

Kubo

et al. 2017

Biological & Pharmaceutical Bulletin

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“…Urate needs to pass through the BBB and/or BCSFB by specific transporters to enter the CSF and brain ISF. Among urate transporters, GLUT9/SLC2A9, urate transporter 1 (URAT1/SLC22A12), and breast cancer resistance protein (BCRP/ABCG2) were reported to play important roles in the regulation of serum uric acid [ 130 , 134 ] and are all expressed in the BBB and/or BCSFB [ 142 , 143 , 144 ].…”

Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

“…An immunohistochemical analysis of mouse brain frozen sections revealed the expression pattern of Glut9 in ependymal cells, tanycytes lining the floor of the ventral third ventricle, and NeuN-positive cells in the brain parenchyma, although submembrane localization (apical or basolateral) was inconclusive [ 143 ]. Furthermore, immunohistochemistry using a methacarn-fixed mouse brain revealed Glut9 expression on the luminal membrane of the brain capillary endothelium [ 143 ]. Although these approaches failed to show Glut9 expression in the CP, the presence of Slc2a9 was identified not only in ependymal cells but, also, in CP epithelial cells by highly sensitive in-situ hybridization [ 143 ].…”

Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

“…Furthermore, immunohistochemistry using a methacarn-fixed mouse brain revealed Glut9 expression on the luminal membrane of the brain capillary endothelium [ 143 ]. Although these approaches failed to show Glut9 expression in the CP, the presence of Slc2a9 was identified not only in ependymal cells but, also, in CP epithelial cells by highly sensitive in-situ hybridization [ 143 ]. We have recently reported the expression of GLUT9 in CP epithelial and ependymal cells of autopsied human brains; however, immunoreactivity signals in the CP were weak and heterogeneous among subjects [ 142 ].…”

Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

“…Although mouse Urat1 was demonstrated to be present in the brain capillaries and CP by immunoblotting [ 156 ], immunohistochemistry data failed to confirm Urat1 expression in these structures [ 144 ]. In contrast, in-situ hybridization revealed Slc22a12 signals in the CP and brain parenchyma, as well as in ependymal cells [ 143 ]. Our immunohistochemical study using autopsied human brains further revealed that URAT1 is located in the basolateral side of CP epithelial cells ( Figure 4 b) [ 142 ].…”

Section: Urate Transporters In Choroid Plexus Epithelial Cellsmentioning

confidence: 99%

See 2 more Smart Citations

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

Chiba

Murakami

Matsumoto

et al. 2020

IJMS

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The choroid plexus plays a central role in the regulation of the microenvironment of the central nervous system by secreting the majority of the cerebrospinal fluid and controlling its composition, despite that it only represents approximately 1% of the total brain weight. In addition to a variety of transporter and channel proteins for solutes and water, the choroid plexus epithelial cells are equipped with glucose, fructose, and urate transporters that are used as energy sources or antioxidative neuroprotective substrates. This review focuses on the recent advances in the understanding of the transporters of the SLC2A and SLC5A families (GLUT1, SGLT2, GLUT5, GLUT8, and GLUT9), as well as on the urate-transporting URAT1 and BCRP/ABCG2, which are expressed in choroid plexus epithelial cells. The glucose, fructose, and urate transporters repertoire in the choroid plexus epithelium share similar features with the renal proximal tubular epithelium, although some of these transporters exhibit inversely polarized submembrane localization. Since choroid plexus epithelial cells have high energy demands for proper functioning, a decline in the expression and function of these transporters can contribute to the process of age-associated brain impairment and pathophysiology of neurodegenerative diseases.

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A New Perspective on the Prediction and Treatment of Stroke: The Role of Uric Acid

Zhu,

Huang,

Zhang

et al. 2024

Neurosci. Bull.

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Immunohistochemical and in situ hybridization study of urate transporters GLUT9/URATv1, ABCG2, and URAT1 in the murine brain

Cited by 14 publications

References 48 publications

Involvement of Carrier-Mediated Transport at the Blood–Cerebrospinal Fluid Barrier in Spermine Clearance from Rat Brain

Involvement of Carrier-Mediated Transport at the Blood–Cerebrospinal Fluid Barrier in Spermine Clearance from Rat Brain

Glucose, Fructose, and Urate Transporters in the Choroid Plexus Epithelium

A New Perspective on the Prediction and Treatment of Stroke: The Role of Uric Acid

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