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Gene expression profiling under low dose and short incubation time of cadmium in primary rat hepatocyte in culture

ABSTRACT: The study was performed using primary rat hepatocyte in culture from 4 adult male Sprague-Dawley rats to investigate the changes in gene expression under low dose (4μM) and short exposure (3hrs) of cadmium chloride. By comparing the gene expression profiles of control and cadmium-treated cells, the most dramatic and significant changes were for those genes associated with transcriptional regulation, antioxidant response and control of protein integrity. Changes in other genes involved in cellular physiological responses such as inflammation, growth and apoptosis were also observed. Results were further confirmed by quantitative real time polymerase chain reaction (qRT-PCR). Keywords: early protective responses

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE8013 | GEO | 2009/02/25

SECONDARY ACCESSION(S): PRJNA100809

REPOSITORIES: GEO

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Project description:Cadmium is a natural element that can accumulate to toxic levels in the environment leading to detrimental effects in animals and humans including kidney, liver and lung injuries. Using a transcriptomics approach, genes and cellular pathways affected by a low dose of cadmium were investigated. Adult largemouth bass were intraperitoneally injected with 20 Âµg/kg of cadmium chloride and microarray analyses were conducted in the liver and testis 48 hours after injection. Transcriptomics profiles identified in response to cadmium treatment were tissue-specific with the most differential expression changes found in the liver tissues, which also contained much higher levels of cadmium than the testes. Acute exposure to a low dose of cadmium induced oxidative stress response and oxidative damage pathways in the liver. The mRNA levels of antioxidants such as catalase increased and numerous transcripts related to DNA damage and DNA repair were significantly altered. Hepatic mRNA levels of metallothionein, a proposed marker of cadmium exposure, showed a small insignificant increase after 48 hours exposure. Carbohydrate metabolic pathways were also disrupted in cadmium-exposed fish with hepatic transcripts such as UDP-glucose pyrophosphorylase 2 and sorbitol dehydrogenase highly induced. Both tissues exhibited a disruption of steroid signalling pathways. In the testis, estrogen receptor beta and transcripts linked to cholesterol metabolism were suppressed. On the contrary, genes involved in cholesterol metabolism were highly increased in the liver including genes encoding for the rate limiting steroidogenic acute regulatory protein and the catalytic enzyme 7-dehydrocholesterol reductase. Integration of the transcriptomics data using functional enrichment analyses revealed a number of enriched gene networks associated with previously reported adverse outcomes of cadmium exposure such as liver toxicity and impaired reproduction. Adult largemouth bass (n=4 per treatment) were ip injected with a single dose of cadmium chloride (20 ug/kg) or a saline solution. After 48 hours, liver and testis were excised and differential gene expression profiles were examined.

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Gene expression profiling under low dose and short incubation time of cadmium in primary rat hepatocyte in culture

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