Effect of cadmium on 24-hour pattern in expression of redox enzyme and clock genes in rat medial basal hypothalamus.
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 microg/day) on 24-h changes in expression of redox pathway enzyme and circadian genes in rat medial basal hypothalamus (MBH). Rats receiving CdCl(2) (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 CdCl(2) 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 CdCl(2) 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.
Jiménez-Ortega
Vanesa
V
Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, Madrid, Spain. jimenezv@med.ucm.es
Cardinali
Daniel P
DP
Fernández-Mateos
María P
MP
Ríos-Lugo
María J
MJ
Scacchi
Pablo A
PA
Esquifino
Ana I
AI
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D019256:Cadmium Chloride / Q000494:pharmacology*; D002374:Catalase / Q000235:genetics / Q000378:metabolism; D002940:Circadian Rhythm / Q000187:drug effects / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D005979:Glutathione Peroxidase / Q000235:genetics / Q000378:metabolism; D005980:Glutathione Reductase / Q000235:genetics / Q000378:metabolism; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics / Q000378:metabolism; D007033:Hypothalamus, Middle / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism
D007527:Isoenzymes; D002374:Catalase; D005979:Glutathione Peroxidase; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D013482:Superoxide Dismutase; D005980:Glutathione Reductase; D019256:Cadmium Chloride