Expression and Localization of Carnitine/Organic Cation Transporter OCTN1 and OCTN2 in Ocular Epithelium

Garrett, Qian; Xu, Shi‐Hai; Simmons, Peter A.; Vehige, Joseph; Flanagan, Judith; Willcox, Mark

doi:10.1167/iovs.07-1528

Cited by 43 publications

(37 citation statements)

References 20 publications

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“…With immunohistochemical analysis, we tested only the expression of OCT-1 and OCT-2. Previous reports showed abundant expression of OCTN-1, OCNT-2, and OCT-3 isoforms in human ocular tissues (Garrett et al, 2008;Zhang et al, 2008;Xu et al, 2010). MPP + used in this study as a substrate for OCT transporter has broad specificity and interacts with both OCT as well as OCTN transporters (Jonker and Schinkel, 2004;Jong et al, 2011).…”

Section: Discussionmentioning

confidence: 91%

RETRACTION: Immunohistochemical and Functional Characterization of Peptide, Organic Cation, Neutral and Basic Amino Acid, and Monocarboxylate Drug Transporters in Human Ocular Tissues

2012

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Since there is paucity of information on solute transporters in human ocular tissues, the aim of this study was immunohistochemical and functional characterization of peptide transporters (PEPT), organic cation transporters (OCTs), neutral and basic amino acid transporters (ATB 0,+ ), and monocarboxylate transporters (MCTs) in human ocular barriers. Immunohistochemical localization of transporters was achieved using 5-mm-thick paraffin-embedded sections of whole human eyes. In vitro transport studies were carried out across human cornea and sclera-choroid-retinal pigment epithelium (SCRPE) using a cassette of specific substrates in the presence and absence of inhibitors to determine the role of transporters in transtissue solute delivery. Immunohistochemistry showed the expression of PEPT-1, PEPT-2, ATB 0,+

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Section: Discussionmentioning

confidence: 91%

RETRACTION: Immunohistochemical and Functional Characterization of Peptide, Organic Cation, Neutral and Basic Amino Acid, and Monocarboxylate Drug Transporters in Human Ocular Tissues

2012

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“…Human OCTN1 is expressed in kidneys, skeletal muscle, placenta, prostate, heart, fetal liver, eyes, and lungs ( Fig. 2) (Tamai et al, 1997;Garrett et al, 2008). There is also prominent expression of human OCTN1 in spleen, bone marrow, and whole blood, with particularly high levels in CD14 ϩ cells (Tokuhiro et al, 2003).…”

Section: Oatp1a2mentioning

confidence: 99%

“…Human OCTN2 is most notably detected in kidneys and placenta and to a lesser degree in other tissues ( Fig. 2) (Tamai et al, 1998;Tokuhiro et al, 2003;Lahjouji et al, 2004;Garrett et al, 2008). Octn2 and OCTN2 proteins are present on the brush border membrane vesicles from kidneys (Tamai et al, 2001a), placental syncytiotrophoblasts , and small intestine enterocytes , as well as the basolateral surface of epididymal cells (Rodríguez et al, 2002) (Table 4).…”

Section: Oatp1a2mentioning

confidence: 99%

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

2010

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“…Located on the luminal side, MATE1 is involved in the renal secretion of creatinine (35) and therapeutic drugs such as metformin (36) and cephalexin (37). Also expressed on the luminal side, OCTN1 is involved in the renal reabsorption of L-carnitine (38) and transport of several chemotherapeutics such as doxorubicin and methotrexate (39). As these organic cation transporters play an important role in the renal clearance of drug substrates, downregulation in their expression could have clinical consequences such as altered systemic drug concentrations and nephrotoxicity.…”

Section: Discussionmentioning

confidence: 99%

Endotoxin Modulates the Expression of Renal Drug Transporters in HIV-1 Transgenic Rats

Pour

Piquette-Miller

2018

J Pharm Pharm Sci

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PURPUSE: Bacterial co-infections and low grade endotoxemia are common in HIV patients. Inflammation due to endotoxin or HIV may influence the expression and activity of transporters. Kidney transporters influence renal drug clearances including many antiretroviral agents. Our objective was to study the effect of endotoxin and HIV on the renal expression of drug transporters in an HIV-transgenic (HIV-Tg) rat model. These rats develop immune dysfunction and AIDS-associated conditions like humans. METHODS: Endotoxin or saline was administered intraperitoneally to HIV-Tg or wild type (WT) littermates and kidneys were collected 18 hours later. Expression of transporters and cytokines were measured by qRT-PCR and Western blots. Serum cytokine levels were measured by ELISA. RESULTS: Endotoxin induced serum levels of IL-6, TNF-α and IFN-γ in both HIV-Tg and WT animals. The basal mRNA expression of Oct2, Oct3, Octn1, Mate1, Urat1 and Ent1was significantly lower (33-60%) and the expression of Ent2 and Pept2 was significantly higher (33-45%) in HIV-Tg as compared to WT. While endotoxin significantly downregulated the mRNA expression of Mdra1 and Pept2 in both HIV and WT groups (69-78%), it imposed a significant reduction on the mRNA expression of Oct2, Oct3, Octn1, Mate1, Oat2, urat1, and Ent1 (54-83%) only in the WT group. Endotoxin significantly increased the mRNA expression of Pept1 (140%) in both WT and HIV groups. CONCLUSIONS: HIV and endotoxin each imposed alterations in the expression of many clinically important renal drug transporters although co-infection did not augment this effect. Viral and/or bacterial infections may impact the renal clearance of drug substrates in patients and could potentially be a source of drug-disease interactions.

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Expression and Localization of Carnitine/Organic Cation Transporter OCTN1 and OCTN2 in Ocular Epithelium

Abstract: This report is the first to document OCTN1 and OCTN2 expression in human corneal and conjunctival epithelial cells. These findings suggest potential involvement of OCTN1 and OCTN2 in the transport of carnitine in ocular tissues.

Cited by 43 publications

References 20 publications

RETRACTION: Immunohistochemical and Functional Characterization of Peptide, Organic Cation, Neutral and Basic Amino Acid, and Monocarboxylate Drug Transporters in Human Ocular Tissues

RETRACTION: Immunohistochemical and Functional Characterization of Peptide, Organic Cation, Neutral and Basic Amino Acid, and Monocarboxylate Drug Transporters in Human Ocular Tissues

Xenobiotic, Bile Acid, and Cholesterol Transporters: Function and Regulation

Endotoxin Modulates the Expression of Renal Drug Transporters in HIV-1 Transgenic Rats

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