pgp - publications

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1. Aquat Toxicol. 2012 Feb 19;114-115C:104-118. [Epub ahead of print]

P-glycoprotein (P-gp) in the monogonont rotifer, Brachionus koreanus: Molecular
characterization and expression in response to pharmaceuticals.

Rhee JS, Jeong CB, Kim BM, Lee JS.

Department of Molecular and Environmental Bioscience, Graduate School, Hanyang
University, Seoul 133-791, South Korea.

P-glycoprotein is involved in the efflux of diverse chemicals, including
hydrophobic compounds and pharmaceuticals as a first line of defense. Here, we
firstly identified and characterized the P-gp (Bk-P-gp) gene in the rotifer,
Brachionus koreanus. Bk-P-gp was highly conserved in genomic organization
compared to the human P-gp gene. Messenger RNA expression of Bk-P-gp revealed
that it would be regulated by temperature change via 14 heat shock response
elements in its promoter region. Bk-P-gp showed a high similarity of
motifs/domains compared to those of vertebrates in its amino acid sequences. To
check whether Bk-P-gp would be inducible, we exposed B. koreanus to six
pharmaceuticals including antibiotics for use in aquaculture and observed dose-
and time-dependency on transcripts of Bk-P-gp for 24h over a wide range of
concentration. Efflux assay and membrane topology supported its conserved
function for transportation of a number of chemicals upon cellular damage. To
reveal the effect of pharmaceuticals on the rotifer, we measured survival rate
and population growth rate after exposure to six pharmaceuticals. In an acute
toxicity test, both NOEC and LC(50) values for all the pharmaceuticals were high
for 24h. ATP, CBZ, SMX, and TMP markedly inhibited the population growth of B.
koreanus after exposure up to 100mg/L for 10 days. In this paper, we demonstrated
that various pharmaceuticals can retard growth rate with up-regulation of the
P-gp gene as a cellular defense system. This finding provides a better
understanding of molecular mechanisms involved in pharmaceutical-mediated
cellular damage in B. koreanus.

Copyright © 2012 Elsevier B.V. All rights reserved.

PMID: 22446822 [PubMed - as supplied by publisher]