Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis Transporters

S. H. Lee, T. Oh, B. Y. Jeon, E. Y. Kwak, W. S. Shim, Sangnae Cho, D. D. Kim, S. J. Chung, C. K. Shim

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

A pulmonary tuberculosis mouse model was used to assess the pharmacodynamic and pharmacokinetic characteristics of tuberculosis therapeutics. While membrane transporters play important roles in drug disposition and physiological homeostasis, their expressional changes and contribution have never been analysed in a tuberculosis animal model. The mRNA expression level of 20 Abc family transporters and 32 Slc family transporters in tuberculosis-infected mice were compared with those in nave uninfected mice using real-time polymerase chain reaction (PCR). Mycobacterium tuberculosis infection induced many dramatic expression changes of families of both Abc transporters and Slc transporters at 4 and 8 weeks, as observed in the livers, kidneys, and intestines of test mice and in a different mode, in the lungs and spleens as well. These changes were dependent on the tuberculosis progression with the tissue-specific manner, that is, in the lungs, the number of transporters of which the expression level changed due to M. tuberculosis infection had increased, and the magnitude of change also greater at 8 weeks, while in the spleen, the transcription of most transporters except Mrps had not changed or had recovered back to the same level of nave transcription at 8 weeks. Understanding the expression changes of transporters will assist in setting up rational preclinical dosing plans through the ability to predict the pharmacokinetics of new anti-tuberculosis chemotherapeutics and, furthermore, will assist in the design of safer and more efficient drug regimens.

Original languageEnglish
Pages (from-to)738-748
Number of pages11
JournalXenobiotica
Volume39
Issue number10
DOIs
Publication statusPublished - 2009 Nov 9

Fingerprint

Pharmacokinetics
Transcription
Pulmonary Tuberculosis
Tuberculosis
Pharmacodynamics
Tissue
Messenger RNA
Membrane Transport Proteins
Polymerase chain reaction
Mycobacterium Infections
Pharmaceutical Preparations
Liver
Animals
Mycobacterium tuberculosis
Spleen
Lung
Intestines
Real-Time Polymerase Chain Reaction
Homeostasis
Animal Models

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Toxicology
  • Pharmacology
  • Health, Toxicology and Mutagenesis

Cite this

Lee, S. H. ; Oh, T. ; Jeon, B. Y. ; Kwak, E. Y. ; Shim, W. S. ; Cho, Sangnae ; Kim, D. D. ; Chung, S. J. ; Shim, C. K. / Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis Transporters. In: Xenobiotica. 2009 ; Vol. 39, No. 10. pp. 738-748.
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Lee, SH, Oh, T, Jeon, BY, Kwak, EY, Shim, WS, Cho, S, Kim, DD, Chung, SJ & Shim, CK 2009, 'Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis Transporters', Xenobiotica, vol. 39, no. 10, pp. 738-748. https://doi.org/10.1080/00498250903089829

Tissue-specific changes in mRNA expression of Abc and Slc transporters in murine pulmonary tuberculosis Transporters. / Lee, S. H.; Oh, T.; Jeon, B. Y.; Kwak, E. Y.; Shim, W. S.; Cho, Sangnae; Kim, D. D.; Chung, S. J.; Shim, C. K.

In: Xenobiotica, Vol. 39, No. 10, 09.11.2009, p. 738-748.

Research output: Contribution to journalArticle

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AU - Shim, C. K.

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