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ZFIN ID: ZDB-PUB-200304-38
The vitamin B6-dependent enzymes PYGL and G6PD fuel NADPH oxidases to promote skin inflammation
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.
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:
  • Animals
  • Animals, Genetically Modified
  • Anti-Inflammatory Agents/pharmacology
  • Anti-Inflammatory Agents/therapeutic use
  • Biopsy
  • Datasets as Topic
  • Disease Models, Animal
  • Gene Expression Profiling
  • Glucosephosphate Dehydrogenase/antagonists & inhibitors
  • Glucosephosphate Dehydrogenase/genetics
  • Glucosephosphate Dehydrogenase/metabolism*
  • Glycogen/metabolism
  • Glycogen Phosphorylase, Liver Form/antagonists & inhibitors
  • Glycogen Phosphorylase, Liver Form/genetics
  • Glycogen Phosphorylase, Liver Form/metabolism*
  • HaCaT Cells
  • Humans
  • Intravital Microscopy
  • NADPH Oxidases/metabolism
  • Oligonucleotide Array Sequence Analysis
  • Oxidative Stress/drug effects
  • Oxidative Stress/immunology
  • Psoriasis/blood
  • Psoriasis/drug therapy
  • Psoriasis/immunology*
  • Psoriasis/pathology
  • Signal Transduction/drug effects
  • Signal Transduction/immunology
  • Skin/diagnostic imaging
  • Skin/drug effects
  • Skin/immunology
  • Skin/pathology
  • Vitamin B 6/blood
  • Vitamin B 6/metabolism*
  • Zebrafish
  • Zebrafish Proteins/metabolism*
PubMed: 32126244 Full text @ Dev. Comp. Immunol.
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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.
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