title: Nanomolar melatonin enhances nNOS expression and controls HaCaT-cells bioenergetics.
abstract: A novel role of melatonin was unveiled, using immortalized human keratinocyte cells (HaCaT) as a model system. Within a time window compatible with its circadian rhythm, melatonin at nanomolar concentration raised both the expression level of the neuronal nitric oxide synthase mRNA and the nitric oxide oxidation products, nitrite and nitrate. On the same time scale, a depression of the mitochondrial membrane potential was detected together with a decrease of the oxidative phosphorylation efficiency, compensated by glycolysis as testified by an increased production of lactate. The melatonin concentration, ∼ nmolar, inducing the bioenergetic effects and their time dependence, both suggest that the observed nitric oxide-induced mitochondrial changes might play a role in the metabolic pathways characterizing the circadian melatonin chemistry.
authors.affiliation: Department of Biochemical Sciences, Sapienza University of Rome, Italy.
authors.forename: Marzia
authors.initials: M
authors.lastname: Arese
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Magnifico
authors.forename: Daniela
authors.initials: D
authors.lastname: Mastronicola
authors.forename: Fabio
authors.initials: F
authors.lastname: Altieri
authors.forename: Caterina
authors.initials: C
authors.lastname: Grillo
authors.forename: Thomas J J
authors.initials: TJ
authors.lastname: Blanck
authors.forename: Paolo
authors.initials: P
authors.lastname: Sarti
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism; D000975:Antioxidants / Q000494:pharmacology*; D015153:Blotting, Western; D002478:Cells, Cultured; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology*; D019344:Lactic Acid / Q000378:metabolism; D008550:Melatonin / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D008928:Mitochondria / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism; D052248:Nitric Oxide Synthase Type I / Q000235:genetics / Q000378:metabolism*; D009573:Nitrites / Q000378:metabolism; D010084:Oxidation-Reduction; D010085:Oxidative Phosphorylation; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000975:Antioxidants; D009573:Nitrites; D012333:RNA, Messenger; D009569:Nitric Oxide; D019344:Lactic Acid; D000255:Adenosine Triphosphate; C496320:NOS1 protein, human; D052248:Nitric Oxide Synthase Type I; D008550:Melatonin