New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo

Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 a...

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Veröffentlicht in:Brain research 2004-10, Vol.1024 (1), p.34-43
Hauptverfasser: Shashoua, Victor E., Adams, David S., Volodina, Natalia V., Li, Hua
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container_title Brain research
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creator Shashoua, Victor E.
Adams, David S.
Volodina, Natalia V.
Li, Hua
description Neurodegenerative, cardiovascular, and age-related disorders have been attributed to the cellular damage caused by elevated production of reactive oxygen species (ROS) and free radicals (FRs). These cannot be adequately defended by existing levels of key antioxidant enzymes. Two peptides, 8 and 14 amino acids long, were synthesized and found to up-regulate, at nanomolar concentrations, superoxide dismutase (SOD) and catalase (CAT) m-RNAs (9- to 12-fold) within 3 h, and then elevate by 5- to 10-fold the protein levels of SOD, CAT, and glutathione peroxidase (GPX) in rat primary cortical cultures. Kinetic studies showed that the peptide up-regulation of all three enzymes appears to be a coordinated process which occurs in vitro and in vivo. We also found that ischemia alone, without added drugs, can lead to enhanced gene expression of SOD, CAT, and GPX. This suggests that the CNS can initiate its own “defense” against ROS and FR. Thus, our peptides may activate such systems, as well as AP-1 transcription factor, reported in earlier findings to lead to “repair” (growth) of injured cells.
doi_str_mv 10.1016/j.brainres.2004.06.086
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subjects Animals
Antioxidants - metabolism
AP-1 transcription factor
Biological and medical sciences
Catalase
Catalase - biosynthesis
Catalase - genetics
Cells, Cultured
Cerebral Cortex - drug effects
Cerebral Cortex - enzymology
Ependymin
Gene Expression Regulation, Enzymologic - drug effects
Gene Expression Regulation, Enzymologic - physiology
Glutathione peroxidase
Glutathione Peroxidase - biosynthesis
Glutathione Peroxidase - genetics
Ischemia effect
Medical sciences
Nervous system involvement in other diseases. Miscellaneous
Neurodegenerative disease
Neurology
Peptide effect
Peptides - pharmacology
Rats
Superoxide dismutase
Superoxide Dismutase - biosynthesis
Superoxide Dismutase - genetics
Up-regulation of antioxidant genes
title New synthetic peptides can enhance gene expression of key antioxidant defense enzymes in vitro and in vivo
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