Organic cation/carnitine transporter OCTN3 is present in astrocytes and is up-regulated by peroxisome proliferators-activator receptor agonist

Januszewicz, Elżbieta; Pająk, Beata; Gajkowska, B; Samluk, Łukasz; Djavadian, R; Hinton, Barry T.; Nałęcz, Katarzyna A.

doi:10.1016/j.biocel.2009.08.020

Cited by 36 publications

(40 citation statements)

References 61 publications

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“…A clear example is that while OCTN3 is a rodent member of the OCTN family, and expressed in rat astrocytes, 76) humans do not appear to have this member. 37) Currently, the understanding of species differences of astrocytic organic ion transporters is premature.…”

Section: Cautionary Notes On Astrocyte Organic Ion Transporter Studiesmentioning

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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Section: Cautionary Notes On Astrocyte Organic Ion Transporter Studiesmentioning

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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“…The polyclonal antibodies against C-terminal peptides of rOctn2 [20] and rOctn3 [10] were raised and affinity purified by GenScript Corporation. Alexa Fluor 568 labeled anti-rabbit and Alexa Fluor 488 labeled anti-mouse antibodies were from Molecular Probes.…”

Section: Materials L-[methyl-mentioning

confidence: 99%

“…The pipette solution containing selected neurons was transferred directly into RNA lysis RTL buffer. Total RNA was isolated with RNeasy Ò Micro Kit and reverse-transcribed as given in [10]. Real-time PCR reactions with primers designed for detection of octn2, octn3, b-actin and 18SRNA [10] were performed with the following thermal conditions: a single cycle at 94°C for 2 min, followed by 35 cycles (denaturation 30 s at 94°C, annealing 30 s at either 52°C for OCTN2 or 51°C for OCTN3 and 30 s at 72°C for extension).…”

Section: Cell Culturementioning

confidence: 99%

“…Moreover, carnitine has been postulated as a neuromodulator and anti-aging medication, increasing levels of certain neurotransmitters in various brain regions [18]. Recently, a different regulatory mechanism has been demonstrated for both high affinity carnitine transporters in astrocytes [10] in comparison with peripheral tissues [19], since only expression of OCTN3 was up-regulated in astrocytes by peroxisome proliferatorsactivator receptor agonist [10]. Taking into account various physiological roles of carnitine, the present study was aimed at verification of expression of octn2 and octn3 genes and presence of both proteins coded by these genes in neurons of suckling and adult rats, i.e.…”

Section: Introductionmentioning

confidence: 99%

“…gradient [8]. Moreover, OCTN3 has been postulated to be a peroxisomal transporter, both in the brain [10] and in peripheral tissues [11]. Expression of octn2 was detected by in situ hybridization in cerebral cortex and cerebellum of 4-week old rats [12].…”

Section: Introductionmentioning

confidence: 99%

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High Affinity Carnitine Transporters from OCTN Family in Neural Cells

et al. 2010

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Neurons are known to accumulate L-carnitine--a compound necessary for transfer of acyl moieties through biological membranes, apart from very low beta-oxidation of fatty acids in adult brain. Present study demonstrates expression of octn2 and octn3 genes coding high affinity carnitine transporters, as well as presence of both proteins in neurons obtained from suckling and adult rats, and also in mouse transformed neural cells. Measurements of carnitine transport show activity of both transporters in neural cells, pointing to their importance in physiological processes other than beta-oxidation.

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