PUBLICATION

Diphenyleneiodonium chloride, an inhibitor of reduced nicotinamide adenine dinucleotide phosphate oxidase, suppresses light-dependent induction of clock and DNA repair genes in zebrafish

Authors
Osaki, T., Uchida, Y., Hirayama, J., and Nishina, H.
ID
ZDB-PUB-110803-43
Date
2011
Source
Biological & pharmaceutical bulletin   34(8): 1343-1347 (Journal)
Registered Authors
Hirayama, Jun
Keywords
circadian clock, flavin-containing oxidase, reduction-oxidation, reactive oxygen species, zebrafish
MeSH Terms
  • Animals
  • CLOCK Proteins
  • Cells, Cultured
  • Chlorides/pharmacology
  • Circadian Clocks/genetics*
  • DNA Repair/genetics*
  • Enzyme Inhibitors/pharmacology
  • Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors
  • Flavin-Adenine Dinucleotide/metabolism
  • Flavins/metabolism*
  • Gene Expression Regulation*
  • Light*
  • Mitogen-Activated Protein Kinases/antagonists & inhibitors
  • NADPH Oxidases/antagonists & inhibitors*
  • Onium Compounds/pharmacology*
  • Oxidation-Reduction
  • Reactive Oxygen Species/metabolism
  • Signal Transduction
  • Zebrafish
PubMed
21804230 Full text @ Biol. Pharm. Bull.
Abstract
In most species, solar light is both a DNA-damaging agent and the key entraining stimulus for the endogenous circadian clock. The zebrafish is an attractive vertebrate system in which to study the influence of light on gene expression because the DNA repair proteins and circadian oscillators in this species are light-responsive. At the molecular level, light treatment of zebrafish cells induces the production of reactive oxygen species (ROS). ROS both alters the reduction–oxidation (redox) state of these cells and stimulates intracellular extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) cascades that transduce photic signals activating the transcription of particular light-responsive genes, including some clock genes and some DNA repair genes involved in photoreactivation. To date, however, the phototransducing molecules responsible for light-dependent ROS production have not been identified. Flavin-containing oxidases, such as reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, are versatile flavoenzymes that catalyze molecular oxidation in numerous metabolic pathways. Importantly, light induces the photoreduction of the flavin adenine dinucleotide (FAD) moiety in these oxidases, leading to ROS production. Here, we show in cultured zebrafish cells that diphenyleneiodonium chloride (DPI), an inhibitor of NADPH oxidase, both suppresses ERK/MAPK activation and efficiently reduces light-dependent expression of clock and photoreactivation genes. Our results suggest that flavin-containing oxidases may be responsible for light-dependent ROS production and thus light-dependent gene expression in zebrafish. Our findings also support the existence of a regulatory link between photoreactivation and the circadian clock in this species.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping