Human renal organic anion transporter 1 (hOAT1) and its role in the nephrotoxicity of antiviral nucleotide analogs

被引：182

作者：

Cihlar, T ^{[1
]}

Ho, ES ^{[1
]}

Lin, DC ^{[1
]}

Mulato, AS ^{[1
]}

机构：

[1] Gilead Sci Inc, Foster City, CA 94404 USA

来源：

NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS | 2001年 / 20卷 / 4-7期

关键词：

D O I：

10.1081/NCN-100002341

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

hOAT1 is a renal membrane protein able to efficiently transport acyclic nucleoside phosphonates (ANPs). When expressed in CHO cells, hOAT1 mediates the uptake and cytotoxicity of ANPs suggesting that it plays an active role in the nephrotoxicity associated with cidofovir CMV therapy and high-dose adefovir HIV therapy. Although efficiently transported by hOAT1, tenofovir did not show any significant cytotoxicity in isolated human proximal tubular cells, which correlates with the lack of nephrotoxicity observed in HIV-infected patients on prolonged tenofovir therapy.

引用

收藏

页码：641 / 648

页数：8

相关论文

共 30 条

[1] 1-[((S)-2-HYDROXY-2-OXO-1,4,2-DIOXAPHOSPHORINAN-5-YL)METHYL]CYTOSINE, AN INTRACELLULAR PRODRUG FOR (S)-1-(3-HYDROXY-2-PHOSPHONYLMETHOXYPROPYL)CYTOSINE WITH IMPROVED THERAPEUTIC INDEX IN-VIVO [J].

BISCHOFBERGER, N ;

HITCHCOCK, MJM ;

CHEN, MS ;

BARKHIMER, DB ;

CUNDY, KC ;

KENT, KM ;

LACY, SA ;

LEE, WA ;

LI, ZH ;

MENDEL, DB ;

SMEE, DF ;

SMITH, JL .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1994, 38 (10) :2387-2391

[2] ELECTROPHYSIOLOGY AND ULTRASTRUCTURE OF CULTURED HUMAN PROXIMAL TUBULE CELLS [J].

BLACKBURN, JG ;

HAZENMARTIN, DJ ;

DETRISAC, CJ ;

SENS, DA .

KIDNEY INTERNATIONAL, 1988, 33 (02) :508-516

[3] Remission of AIDS-associated progressive multifocal leukoencephalopathy after cidofovir therapy [J].

Brambilla, AM ;

Castagna, A ;

Novati, R ;

Cinque, P ;

Terreni, MR ;

Moioli, MC ;

Lazzarin, A .

JOURNAL OF NEUROLOGY, 1999, 246 (08) :723-725

[4] The antiviral nucleotide analogs cidofovir and adefovir are novel substrates for human and rat renal organic anion transporter 1 [J].

Cihlar, T ;

Lin, DC ;

Pritchard, JB ;

Fuller, MD ;

Mendel, DB ;

Sweet, DH .

MOLECULAR PHARMACOLOGY, 1999, 56 (03) :570-580

[5] METABOLISM OF 1-(S)-(3-HYDROXY-2-PHOSPHONOMETHOXYPROPYL)-CYTOSINE (HPMPC) IN HUMAN EMBRYONIC LUNG-CELLS [J].

CIHLAR, T ;

VOTRUBA, I ;

HORSKA, K ;

LIBOSKA, R ;

ROSENBERG, I ;

HOLY, A .

COLLECTION OF CZECHOSLOVAK CHEMICAL COMMUNICATIONS, 1992, 57 (03) :661-672

[6]

Cundy KC, 1996, DRUG METAB DISPOS, V24, P745

[7] CLINICAL PHARMACOKINETICS OF CIDOFOVIR IN HUMAN IMMUNODEFICIENCY VIRUS-INFECTED PATIENTS [J].

CUNDY, KC ;

PETTY, BG ;

FLAHERTY, J ;

FISHER, PE ;

POLIS, MA ;

WACHSMAN, M ;

LIETMAN, PS ;

LALEZARI, JP ;

HITCHCOCK, MJM ;

JAFFE, HS .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (06) :1247-1252

[8]

Cundy KC, 1996, DRUG METAB DISPOS, V24, P315

[9] CLINICAL PHARMACOKINETICS OF ADEFOVIR IN HUMAN-IMMUNODEFICIENCY-VIRUS TYPE 1-INFECTED PATIENTS [J].

CUNDY, KC ;

BARDITCHCROVO, P ;

WALKER, RE ;

COLLIER, AC ;

EBELING, D ;

TOOLE, J ;

JAFFE, HS .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 1995, 39 (11) :2401-2405

[10] Clinical pharmacokinetics of the antiviral nucleotide analogues cidofovir and adefovir [J].

Cundy, KC .

CLINICAL PHARMACOKINETICS, 1999, 36 (02) :127-143