24-Hour variation in gene expression of redox pathway enzymes in rat hypothalamus: effect of melatonin treatment.
The 24-h changes in medial basal hypothalamic (MBH) gene expression of redox pathway enzymes nitric oxide synthase (NOS)-1 and NOS-2, heme oxygenase (HO)-1 and HO-2, Cu/Zn- and Mn-superoxide dismutases (SOD) and catalase were examined in adult male Wistar rats kept under an alternating regimen of light/dark. Half of the animals received melatonin (approximately 60 microg/day) in the drinking water. After 1 month, rats were killed at six different time intervals, throughout a 24-h cycle. MBH mRNA levels were measured by real-time PCR analysis. In controls, gene expression of NOS-2 and HO-2 peaked at the early light phase while that of HO-1 showed a maximum at the middle of the dark phase. None of MBH mRNAs encoding NOS-1, Cu/Zn-SOD, Mn-SOD and catalase exhibited significant 24-h variations in control rats. Melatonin administration decreased significantly mRNAs for NOS-1, NOS-2, HO-1 and HO-2 as well as changed their 24-h profile. Melatonin augmented gene expression of the antioxidant enzymes Cu/Zn-SOD, Mn-SOD or catalase at certain time intervals only. The results are compatible with the view that the principal indirect (i.e. gene expression of redox pathway enzymes) effect of melatonin on redox pathway in the hypothalamus is mainly exerted via down-regulation of pro-oxidant enzyme mRNAs.
Jiménez-Ortega
Vanesa
V
Department of Biochemistry and Molecular Biology III, School of Medicine, Universidad Complutense, Madrid, Spain.
Cano
Pilar
P
Cardinali
Daniel P
DP
Esquifino
Ana I
AI
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000235:genetics; D007031:Hypothalamus / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D008550:Melatonin / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000235:genetics; D010084:Oxidation-Reduction / Q000187:drug effects; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000235:genetics
D000975:Antioxidants; D012333:RNA, Messenger; D019001:Nitric Oxide Synthase; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2; D013482:Superoxide Dismutase; D008550:Melatonin