Effect of cadmium on 24-hour pattern in expression of redox enzyme and clock genes in rat medial basal hypothalamus
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The effect of cadmium (Cd) in the brain has been attributed to an increase in reactive oxygen species in cells, particularly when high amounts of the metal are given. In this study we examined the effect of a low dose of Cd (7.5 μg/day) on 24-h changes in expression of redox pathway enzyme and circadian genes in rat medial basal hypothalamus (MBH). Rats receiving CdCl2 (5 ppm in drinking water) or tap water for 1 month were killed at six different time intervals throughout a 24 h cycle. MBH mRNA levels were measured by real-time PCR analysis. In CdCl2 treated rats a disruption of 24-h pattern of hypothalamic gene expression of nitric oxide synthase (NOS)-1 and -2, heme oxygenase (HO)-1 and -2, Mn- superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione reductase was detectable. Mean levels of MBH mRNA for HO-2, Mn-SOD and catalase augmented after Cd intake, whereas those of NOS-2 decreased. After CdCl2 intake rats the 24-h pattern of clock gene expression in MBH seen in controls was significantly suppressed (Bmal1) or changed in phase (Per1, Per2, Cry2) while in the case of Clock significant 24-h variations were induced. The results are compatible with the view that a low amount of Cd given in tap water brought about significant changes in circadian expression of redox enzyme and clock genes in rat MBH. © Springer Science Business Media, LLC. 2010.
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The effect of cadmium (Cd) in the brain has been attributed to an increase in reactive oxygen species in cells, particularly when high amounts of the metal are given. In this study we examined the effect of a low dose of Cd (7.5 μg/day) on 24-h changes in expression of redox pathway enzyme and circadian genes in rat medial basal hypothalamus (MBH). Rats receiving CdCl2 (5 ppm in drinking water) or tap water for 1 month were killed at six different time intervals throughout a 24 h cycle. MBH mRNA levels were measured by real-time PCR analysis. In CdCl2 treated rats a disruption of 24-h pattern of hypothalamic gene expression of nitric oxide synthase (NOS)-1 and -2, heme oxygenase (HO)-1 and -2, Mn- superoxide dismutase (SOD), catalase, glutathione peroxidase and glutathione reductase was detectable. Mean levels of MBH mRNA for HO-2, Mn-SOD and catalase augmented after Cd intake, whereas those of NOS-2 decreased. After CdCl2 intake rats the 24-h pattern of clock gene expression in MBH seen in controls was significantly suppressed (Bmal1) or changed in phase (Per1, Per2, Cry2) while in the case of Clock significant 24-h variations were induced. The results are compatible with the view that a low amount of Cd given in tap water brought about significant changes in circadian expression of redox enzyme and clock genes in rat MBH. © Springer Science%2bBusiness Media, LLC. 2010.
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Cadmium; Catalase; Circadian rhythms; Clock genes; Gene expression; Glutathione peroxidase; Glutathione reductase; Heme oxygenase; Medial basal hypothalamus; Nitric oxide synthase; Superoxide dismutase beta actin; cadmium; cadmium chloride; catalase; copper zinc superoxide dismutase; cryptochrome 2; glutathione peroxidase; glutathione reductase; heme oxygenase 1; heme oxygenase 2; inducible nitric oxide synthase; manganese superoxide dismutase; messenger RNA; neuronal nitric oxide synthase; oxidoreductase; PER1 protein; PER2 protein; protein BMAL1; tap water; transcription factor CLOCK; cadmium chloride; catalase; glutathione peroxidase; glutathione reductase; heme oxygenase; isoenzyme; nitric oxide synthase; superoxide dismutase; animal experiment; animal tissue; article; circadian rhythm; controlled study; early photophase; early scotophase; gene expression; hypothalamus; late scotophase; male; nonhuman; protein expression; rat; real time polymerase chain reaction; time; Wistar rat; animal; biological rhythm; drug effect; gene expression regulation; genetics; metabolism; oxidation reduction reaction; physiology; Rattus; Animals; Biological Clocks; Cadmium Chloride; Catalase; Circadian Rhythm; Gene Expression Regulation, Enzymologic; Glutathione Peroxidase; Glutathione Reductase; Heme Oxygenase (Decyclizing); Hypothalamus, Middle; Isoenzymes; Male; Nitric Oxide Synthase; Oxidation-Reduction; Rats; Rats, Wistar; Superoxide Dismutase
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