PUBLICATION
The vitamin B6-dependent enzymes PYGL and G6PD fuel NADPH oxidases to promote skin inflammation
- Authors
- Martínez-Navarro, F.J., Martínez-Morcillo, F.J., López-Muñoz, A., Pardo-Sánchez, I., Martínez-Menchón, T., Corbalán-Vélez, R., Cayuela, M.L., Pérez-Oliva, A.B., García-Moreno, D., Mulero, V.
- ID
- ZDB-PUB-200304-38
- Date
- 2020
- Source
- Developmental and comparative immunology 108: 103666 (Journal)
- Registered Authors
- Mulero, Victor
- Keywords
- G6PD, Hydrogen peroxide, Inflammation, Neutrophils, Nfkb, Oxidative stress, PYGL, Psoriasis, Skin, Vitamin B6, Zebrafish
- MeSH Terms
-
- Oligonucleotide Array Sequence Analysis
- Datasets as Topic
- Gene Expression Profiling
- Biopsy
- Psoriasis/blood
- Psoriasis/drug therapy
- Psoriasis/immunology*
- Psoriasis/pathology
- Oxidative Stress/drug effects
- Oxidative Stress/immunology
- Zebrafish Proteins/metabolism*
- Glycogen Phosphorylase, Liver Form/antagonists & inhibitors
- Glycogen Phosphorylase, Liver Form/genetics
- Glycogen Phosphorylase, Liver Form/metabolism*
- Disease Models, Animal
- Glycogen/metabolism
- Animals, Genetically Modified
- Intravital Microscopy
- Animals
- HaCaT Cells
- Glucosephosphate Dehydrogenase/antagonists & inhibitors
- Glucosephosphate Dehydrogenase/genetics
- Glucosephosphate Dehydrogenase/metabolism*
- Skin/diagnostic imaging
- Skin/drug effects
- Skin/immunology
- Skin/pathology
- Anti-Inflammatory Agents/pharmacology
- Anti-Inflammatory Agents/therapeutic use
- NADPH Oxidases/metabolism
- Humans
- Signal Transduction/drug effects
- Signal Transduction/immunology
- Vitamin B 6/blood
- Vitamin B 6/metabolism*
- Zebrafish
- PubMed
- 32126244 Full text @ Dev. Comp. Immunol.
Citation
Martínez-Navarro, F.J., Martínez-Morcillo, F.J., López-Muñoz, A., Pardo-Sánchez, I., Martínez-Menchón, T., Corbalán-Vélez, R., Cayuela, M.L., Pérez-Oliva, A.B., García-Moreno, D., Mulero, V. (2020) The vitamin B6-dependent enzymes PYGL and G6PD fuel NADPH oxidases to promote skin inflammation. Developmental and comparative immunology. 108:103666.
Abstract
Psoriasis is a skin inflammatory disorder that affects 3% of the human population. Although several therapies based on the neutralization of proinflammatory cytokines have been used with relative success, additional treatments are required. The in silico analysis of gene expression data of psoriasis lesional skin and an analysis of vitamin B6 metabolites in the sera of psoriasis patients point to altered vitamin B6 metabolism at both local and systemic levels. Functional studies showed that vitamin B6 vitamers reduced skin neutrophil infiltration, oxidative stress and Nfkb activity in two zebrafish models of skin inflammation. Strikingly, inhibition of glycogen phosphorylase L (Pygl) and glucose-6-phosphate dehydrogenase (G6pd), two vitamin B6-dependent enzymes, alleviated oxidative-stress induced inflammation in zebrafish skin inflammation models. Despite the central role of G6pd in antioxidant defenses, the results of the study demonstrate that glycogen stores and G6pd fuel NADPH oxidase to promote skin inflammation, revealing novel targets for the treatment of skin inflammatory disorders.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping