Antioxidant and cytoprotective responses to redox stress.
Aerobic cells produce reactive oxygen species as a consequence of normal cellular metabolism, and an array of antioxidant systems are in place to maintain the redox balance. When the redox equilibrium of the cell is upset by pro-oxidant environmental stimuli, adaptive responses to the redox stress take place, which can result in up-regulation of antioxidant proteins and detoxification enzymes. Over the past few years, it has become apparent that members of the CNC (cap 'n' collar)-basic leucine zipper family of transcription factors are principal mediators of defensive responses to redox stress. In mammals, the CNC family members nuclear factor-erythroid 2 p45-related factors 1 and 2 (Nrf1 and Nrf2) have been shown to be involved in the transcriptional up-regulation of cytoprotective genes including those encoding glutamate cysteine ligase, NAD(P)H:quinone oxidoreductase, glutathione S-transferases and aldo-keto reductases. An evolutionarily conserved system exists in Caenorhabditis elegans, and it is possible that Drosophila melanogaster may also utilize CNC transcription factors to induce antioxidant genes in response to pro-oxidant chemicals. The advent of microarray and proteomic technologies has advanced our understanding of the gene batteries regulated by oxidative insult, but has highlighted the complexity of gene regulation by environmental factors. This review focuses on the antioxidant response to environmental stress, and the impact that microarrays and proteomics have made in this field.
Mathers
Joanne
J
Biomedical Research Centre, University of Dundee, Ninewells Hospital and Medical School, Dundee DD I 9SY, U.K.
Fraser
Jennifer A
JA
McMahon
Michael
M
Saunders
Robert D C
RD
Hayes
John D
JD
McLellan
Lesley I
LI
D000818:Animals; D000975:Antioxidants / Q000378:metabolism* / Q000494:pharmacology; D019610:Cytoprotection / Q000502:physiology*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism / Q000494:pharmacology; D004781:Environmental Exposure / Q000009:adverse effects; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D020411:Oligonucleotide Array Sequence Analysis; D010084:Oxidation-Reduction / Q000187:drug effects*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D040901:Proteomics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D012097:Repressor Proteins / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction / Q000502:physiology; D015534:Trans-Activators / Q000235:genetics / Q000378:metabolism
D000975:Antioxidants; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D051266:Nuclear Respiratory Factor 1; D051264:Nuclear Respiratory Factors; D017382:Reactive Oxygen Species; D012097:Repressor Proteins; D015534:Trans-Activators; C116463:cnc protein, Drosophila