Characterization of ochratoxin A transport by human organic anion transporters

Jung, Kyu Yong; Takeda, Michio; Kim, Do Kyung; Tojo, Akihiro; Narikawa, Shinichi; Yoo, Byung Sun; Hosoyamada, Makoto; Ho, Seok; Sekine, Takashi; Endou, Hitoshi

doi:10.1016/s0024-3205(01)01296-6

Cited by 98 publications

(70 citation statements)

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“…We have demonstrated that the cytoplasmic membranes of S 2 hOAT1 and S 2 hOAT3 were stained with polyclonal antibodies against hOAT1 and hOAT3, respectively (24). Light-microscopic analysis of the hOAT1 and hOAT3 was performed as previously described (24,25). Briefly, the sections (2 mm) were cut and stained by the labeled streptavidin-biotin method.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

et al. 2003

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Abstract. The purpose of the present study was to elucidate the expression of human organic anion transporter 1 (hOAT1) and hOAT3 in the choroid plexus of the human brain and their interactions with neurotransmitter metabolites using stable cell lines. Immunohistochemical analysis revealed that hOAT1 and hOAT3 are expressed in the cytoplasmic membrane and cytoplasm of human choroid plexus. Neurotransmitter metabolites, namely, 5-methoxyindole-3-acetic acid (5-MI-3-AA), homovanillic acid (HVA), vanilmandelic acid (VMA), 3,4-dihydroxyphenylacetic acid (DOPAC), 5-hydroxyindole-3-acetic acid (5-HI-3-AA), N-acetyl-5-hydroxytryptamine (NA-5-HTT), melatonin, 5-methoxytryptamine (5-MTT), 3,4-dihidroxymandelic acid (DHMA), 5-hydroxytryptophol, and 5-methoxytryptophol (5-MTP), but not methanephrine (MN), normethanephrine (NMN), and 3-methyltyramine (3-MT), at 2 mM, inhibited para-aminohippuric acid uptake mediated by hOAT1. On the other hand, melatonin, 5-MI-3-AA, NA-5-HTT, 5-MTT, 5-MTP, HVA, 5-HI-3-AA, VMA, DOPAC, 5-hydroxytryptophol, and MN, but not 3-MT, DHMA, and NMN, at 2 mM, inhibited estrone sulfate uptake mediated by hOAT3. Differences in the IC 50 values between hOAT1 and hOAT3 were observed for DHMA, DOPAC, HVA, 5-HI-3-AA, melatonin, 5-MI-3-AA, 5-MTP, 5-MTT, and VMA. HOAT1 and hOAT3 mediated the transport of VMA but not HVA and melatonin. These results suggest that hOAT1 and hOAT3 are involved in the efflux of various neurotransmitter metabolites from the cerebrospinal fluid to the blood across the choroid plexus.

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Section: Immunohistochemistrymentioning

confidence: 99%

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

et al. 2003

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“…In addition, we have already found that there is no interspecies difference in the transport property of ochratoxin A by OAT1 between humans and rats, that is, the K m values were 0.57 and 0.42 µM, respectively (10,12). Further studies are necessary to clarify the effects of mycotoxins in the body using animal models like rats.…”

Section: Discussionmentioning

confidence: 96%

Interactions of Organic Anion Transporters and Organic Cation Transporters With Mycotoxins

et al. 2008

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Abstract. Mycotoxins are secondary metabolites of moulds that which exert adverse effects in humans and animals. It is known that direct cellular toxicity is often associated with increased cellular accumulation of toxic compounds, and membrane transport may be the first fundamental stage in the development of the cytotoxicity. To elucidate the entry pathway for mycotoxins into cells, we have investigated the interactions of human and rat organic anion transporters (hOATs/ rOats) and human organic cation transporters (hOCTs) with mycotoxins using cells stably expressing hOATs / rOats / hOCTs. The mycotoxins tested were aflatoxin B1, α-zearalenol, citrinin, citrioveridine, cyclopiazonic acid, fumonisin B1, gliotoxin, patulin, penicillic acid, rubratoxin B, and zearalenone. These mycotoxins inhibited organic anion uptake mediated by hOAT1-4, and organic cation uptake mediated by hOCT1-2. By comparing the IC 50 values of mycotoxins for hOATs, it was found that hOAT1 and hOAT3 exhibited higher affinity interactions with mycotoxins than hOAT2 and hOAT4. There was no interspecies difference between humans and rats for the interactions of OATs with mycotoxins except that of OAT3 with rubratoxin B. Finally, we observed that hOAT1-4 and hOCT1-2 mediated the uptake of aflatoxin B1. In conclusion, hOATs and hOCTs interacted with various mycotoxins. Considering the localization of hOATs / rOats and hOCTs, it was suggested that these transporters were the possible entrance pathway for mycotoxins in kidney and liver, leading to the induction of adverse effects in humans and rats.

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“…1C). It is notable that this K m for NPT4 is much higher than those for other OTxA uptake transporters hOAT1 (0.42 μM), hOAT3 (0.75 μM), and hOAT4 (22.9 μM) (10,11).…”

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confidence: 79%

“…2A, compounds (0.5 to 10 mM) tested here inhibited the [ 3 H]OTxA (0.1 μM) uptake at different ratios: piroxicam and indomethacin inhibited strongly; probenecid (1 mM) and citrinin, moderately; and aspartame, octanoic acid, and cimetidine, weakly. This inhibitory profile of hNPT4 is more similar to that of hOAT4 (except citrinin) (11) than those of hOAT1 and hOAT3 (10), suggesting that the substrate selectivity of hNPT4 is similar to that of hOAT4. Among these drugs, piroxicam and indomethacin inhibited strongly OTxA transport and hNPT4 does not seem to be the potential target of NSAIDs for the nephrotoxicity because of its low affinities for these drugs (IC 50 values: 26.3 μM for piroxicam and 25.8 μM for indomethacin) (Fig.…”

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confidence: 81%

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A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A

et al. 2011

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Abstract. In the present study, we investigated the transport of nephrotoxic mycotoxin ochratoxin A (OTxA) by a novel human organic anion transporter hNPT4 using the Xenopus oocyte expression system. hNPT4 mediated time-and concentration-dependent uptake of OTxA (K m : 802.8 μM) in a pH-and voltage-sensitive manner. Cis-inhibition experiments suggest that the substrate selectivity of hNPT4 is similar to that of hOAT4. The fact that the K m of OTxA for the efflux transporter hNPT4 was much higher than those for the uptake transporters hOAT1 and hOAT3 may favor the accumulation of OTxA in the tubular cell and lead to nephrotoxicity.

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Characterization of ochratoxin A transport by human organic anion transporters

Cited by 98 publications

References 0 publications

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

Expression of Human Organic Anion Transporters in the Choroid Plexus and Their Interactions With Neurotransmitter Metabolites

Interactions of Organic Anion Transporters and Organic Cation Transporters With Mycotoxins

A Novel Human Organic Anion Transporter NPT4 Mediates the Transport of Ochratoxin A

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