PUBLICATION
Sublethal levels of cadmium down-regulate the gene expression of DNA mismatch recognition protein MutS homolog 6 (MSH6) in zebrafish (Danio rerio) embryos
- Authors
- Hsu, T., Tsai, H.T., Huang, K.M., Luan, M.C., and Hsieh, C.R.
- ID
- ZDB-PUB-100811-16
- Date
- 2010
- Source
- Chemosphere 81(6): 748-754 (Journal)
- Registered Authors
- Hsu, Todd
- Keywords
- Cadmium, DNA mismatch repair, Embryo, MSH2, MSH6, Zebrafish
- MeSH Terms
-
- Animals
- Cadmium/toxicity*
- DNA-Binding Proteins/genetics*
- DNA-Binding Proteins/metabolism
- Embryo, Nonmammalian/metabolism*
- Gene Expression/drug effects*
- RNA, Messenger/metabolism
- Water Pollutants, Chemical/toxicity*
- Zebrafish/genetics*
- Zebrafish/metabolism
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 20696460 Full text @ Chemosphere
Citation
Hsu, T., Tsai, H.T., Huang, K.M., Luan, M.C., and Hsieh, C.R. (2010) Sublethal levels of cadmium down-regulate the gene expression of DNA mismatch recognition protein MutS homolog 6 (MSH6) in zebrafish (Danio rerio) embryos. Chemosphere. 81(6):748-754.
Abstract
MutS homolog 6 (MSH6) is the major mismatch contacting component of the MSH2-MSH6 heterodimeric complex (MutSalpha) that mediates DNA mismatch repair (MMR) of simple mispairs and small insertion-deletion loops in eukaryotes. This study examined the potential of cadmium (Cd) to disturb the gene expression of MSH6 in vertebrates using zebrafish (Danio rerio) embryo as a model organism. Semiquantitative RT-PCR indicated that msh2 and msh6 expressions were suppressed in embryos at 1h post fertilization (hpf), then drastically up-regulated in 2hpf embryos and actively expressed in 3-25hpf embryos. In the presence of a constitutive beta-actin expression, exposure of 1hpf embryos to sublethal concentrations of CdCl(2) at 0.5-3muM for 4 or 9h caused a time and concentration-dependent down-regulation of msh6 transcription. Cd failed to inhibit msh2 transcription except at 3muM, reflecting the higher sensitivity of msh6 than msh2 transcription to Cd. Whole mount in situ hybridization showed a wide distribution of msh6 transcripts in the front body portions of 10hpf embryos and Cd-induced a general suppression of msh6 expression in zebrafish tissues. Cd-induced down-regulation of msh6 transcription paralleled with reduced levels of MSH6 protein synthesis and MSH6-mediated G-T mismatch binding activities identified by band shift assay using recombinant zebrafish MSH6 and an anti-human MSH6 antibody. Our results revealed the inhibition of Cd on MSH6 expression at both mRNA and protein levels and this mechanism may play a role in Cd genotoxicity.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping