Early sensing and gene expression profiling under a low dose of cadmium exposure.
Cadmium (Cd) has been shown to have various detrimental effects on health. In recent years progress has been made in dissecting apart the molecular mechanisms underlying the effects of exposure to this toxic metal. In this paper we investigated changes in gene expression using a global transcript profiling approach to better understand the early molecular events that occur in primary rat hepatocytes when exposed to Cd at a concentration (4 microM) and time (3 h) that is prior to any significant increase in cytotoxic parameters. Gene expression changes were most dramatically noticed for proteins involved in transcriptional regulation, zinc finger protein production, and heat shock protein expression. Other genes whose expression changed significantly were those associated with maintaining cellular redox homeostasis such as increasing glutathione synthesis and antioxidant capacity, facilitating the survival or death response, and repairing damage or stimulating degradation. Expression changes were confirmed for selected genes in various groups utilizing qRT-PCR. Various times of Cd incubation were also used to assess the extent of the impact. To define whether or not any of these changes were associated with cadmium's ability to disturb the redox balance, we also tested the effects of Cd in the presence of a blocker of glutathione synthesis, D,L-buthionine-(S,R)-sulfoximine (BSO), and an antioxidant, N-acetylcysteine (NAC). The results show that the Cd induction of some genes can be categorized as occurring primarily in response to changes in the redox state as measured by attenuation of the response by the addition of NAC or to the availability of reduced glutathione as measured by the increase in response in the presence of BSO.
Hsiao
Chin-ju J
CJ
Department of Biological Sciences, Western Michigan University, Kalamazoo, MI 49008, USA.
Stapleton
Susan R
SR
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002104:Cadmium / Q000633:toxicity*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D008297:Male; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism; D013997:Time Factors
D000975:Antioxidants; D004791:Enzyme Inhibitors; D002104:Cadmium; D019328:Buthionine Sulfoximine; D000111:Acetylcysteine