Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Lu, Wen-Jen; Tamai, Ikumi; Nezu, Jun-ichi; Lai, Ming-Liang; Huang, Jin‐ding

doi:10.1007/s11373-006-9071-0

Cited by 35 publications

(24 citation statements)

References 39 publications

(51 reference statements)

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“…Second, the uptake of Sb(III) was 10-times higher than that of Sb(V) in the non-toxic condition, whereas it was 2.8-times higher in the toxic condition. A similar uptake has been reported for As in HEK-293 cells, as it was 2-times higher for As(III) than that for As(V) (Lu et al, 2006).…”

Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) supporting

confidence: 85%

“…At the higher concentrations, the activity was decreased to 48 ± 7% at 10 μM and to 2 ± 7 % at 18 μM, with numerous morphological changes and strong cell damage. The median lethal concentration (LC 50 ) estimated for Sb(III) reached 9.15 μM, close to the LC 50 value of As(III) in the HEK-293 cell line (10.9 μM) (Lu et al, 2006). In the case of Sb (V), the dose-response curve was quite different from that of Sb(III) at lower concentrations of 1-3 μM.…”

Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) supporting

confidence: 61%

“…This activity was maintained at approximately 100% up to 500 μM without significant morphological changes. In contrast to the effects of trivalent species of Sb and As, the LC 50 value of As(V) in HEK-293 cells was reported to be 98.1 μM (Lu et al, 2006). According to the results of this assay, the optimal concentration for further studies was estimated to be 10 μM for Sb(III) and Sb(V).…”

Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) mentioning

confidence: 83%

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Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

2016

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-Antimony cytotoxicity was assessed in human embryonic kidney cells . Uptake, mitochondrial respiratory activity, ROS generation and diffusional kinetics were measured using fluorescence recovery after photobleaching (FRAP). Furthermore, the toxic effect induced by Sb was compared with As toxicity in regard to ROS generation and diffusional kinetics, which provides information on the protein aggregation process. Our results show a favored uptake of Sb(III) and a more severe effect, decreasing the mitochondrial activity more than in the presence of Sb(V). In comparison with As, the Sb species did not generate a significant increase in ROS generation, which was observed with As(III) and As(V). FRAP analysis yielded important information on the diffusion and binding dynamics of live cells in presence of these metalloids. The mobile fraction showed a strong decrease with the As species and Sb(III). The diffusion rate and the k off-rate were significantly decreased for the As and Sb species but were more strong in the presence of As(III).

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Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) supporting

confidence: 85%

Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) supporting

confidence: 61%

Section: Mitochondrial Activity In the Presence Of Sb(iii) And Sb(v) mentioning

confidence: 83%

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Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

2016

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“…To date, however, many studies of RMP hepatotoxicity have concentrated on the transporters that export RMP, and few studies have been published concerning the importance of the transporters that uptake RMP. In fact, RMP inhibits the uptake of bile acids by OATP1B1 (14). For example, RMP inhibits OATP1B1-mediated substrate uptake into the liver in a Xenopus laevis oocyte expression system (13 uptake of bilirubin and RMP, thus directly leading to changes in the susceptibility to RMP hepatotoxicity (15).…”

Section: Introductionmentioning

confidence: 99%

SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury

Chen

Deng

et al. 2012

Mol Med Report

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Abstract. The organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) plays an important role in the transport of endogenous and xenobiotic compounds, such as bile acids and rifampin. In this study, the association between OATP1B1 polymorphisms and rifampin hepatotoxicity was investigated using integrated population genetic analysis and functional studies. A total of 273 unrelated patients treated with rifampin were recruited. The allele frequencies were examined in patients with drug (rifampin)-induced liver injury (DILI) (n=118) and without (non-DILI) (n=155). Functional analyses were conducted to determine whether the inhibition of bile acids by rifampin was associated with OATP1B1 variants. In the present study, 24 single nucleotide polymorphisms (SNPs) in OATP1B1 were detected in a Chinese population, with two of them causing an amino acid change (rs2306283 and rs4149056). The haplotypes constructed by these two SNPs were OATP1B1 IntroductionRifampin (RMP) is one of the major antituberculosis drugs, a second-choice antistaphylococcal agent and an effective medicine in controlling pruritus in primary biliary cirrhosis (1-3). The common adverse reactions to RMP include fever, nausea, vomiting, diarrhea, abdominal pain, hemolytic anemia, thrombocytopenia, liver injury and tubular defects. The hepatotoxicity induced by RMP was first reported in 1971, and it has an incidence rate of 5 to 12.5% (4,5). RMP-induced hepatotoxicity can be divided into three categories: hepatocellular, cholestatic or mixed-type injury (6). In spite of the well-accepted toxicity of RMP in vivo, its toxic mechanism remains unclear. Recently, one important mechanism was determined to be a rise in serum bilirubin via competitive inhibition of hepatocyte bilirubin transport by RMP (7). The inhibition of the hepatic uptake of bile acid has been proposed as the mechanism responsible for RMP-induced cholestasis (8). Notably, the genetic polymorphisms of bile acid transporters have been reported to be closely related to the susceptibility to RMP hepatotoxicity (9).Organic anion transporting polypeptide 1B1 (OATP1B1, encoded by SLCO1B1) is one of the most important bile acid transporters. It is mainly expressed on the basolateral membrane of human hepatocytes and is responsible for bilirubin uptake (10,11). Several studies have demonstrated that OATP1B1 plays an important role in the hepatic uptake of RMP (12). In particular, it has displayed a great capability for RMP transport in HeLa cells, with RMP uptake being markedly decreased by the OATP1B1 allelic variants (13). To date, however, many studies of RMP hepatotoxicity have concentrated on the transporters that export RMP, and few studies have been published concerning the importance of the transporters that uptake RMP. In fact, RMP inhibits the uptake of bile acids by OATP1B1 (14). For example, RMP inhibits OATP1B1-mediated substrate uptake into the liver in a Xenopus laevis oocyte expression system (13

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“…Additionally, OATPB (Calatayud et al, 2012) and OATPC (Lu et al, 2006), two human members of the organic anion transporting polypeptide family that mediate the transmembrane transport of a wide range of amphipathic endogenous and exogenous organic compounds (Hagenbuch and Meier, 2004), are also involved in As(III) influx.…”

Section: Saccharomyces Cerevisiae As(v) Enters the Cell Via The Phosmentioning

confidence: 99%

Mechanisms of Arsenic Detoxification and Resistance

Pillai¹

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Organic anion transporting polypeptide-C mediates arsenic uptake in HEK-293 cells

Cited by 35 publications

References 39 publications

Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

Mechanisms underlying the toxic effects of antimony species in human embryonic kidney cells (HEK-293) and their comparison with arsenic species

SLCO1B1 *15 haplotype is associated with rifampin-induced liver injury

Mechanisms of Arsenic Detoxification and Resistance

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