Macrophage glucose-6-phosphate dehydrogenase stimulates proinflammatory responses with oxidative stress

Mira Ham, Joo Won Lee, A. Hyun Choi, Hagoon Jang, Goun Choi, Jiyoung Park, Chisayo Kozuka, Dorothy D. Sears, Hiroaki Masuzaki, Jae Bum Kima

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35 Scopus citations

Abstract

Glucose-6-phosphate dehydrogenase (G6PD) is a key enzyme that regulates cellular redox potential. In this study, we demonstrate that macrophage G6PD plays an important role in the modulation of proinflammatory responses and oxidative stress. The G6PD levels in macrophages in the adipose tissue of obese animals were elevated, and G6PD mRNA levels positively correlated with those of proinflammatory genes. Lipopolysaccharide (LPS) and free fatty acids, which initiate proinflammatory signals, stimulated macrophage G6PD. Overexpression of macrophage G6PD potentiated the expression of proinflammatory and prooxidative genes responsible for the aggravation of insulin sensitivity in adipocytes. In contrast, when macrophage G6PD was inhibited or suppressed via chemical inhibitors or small interfering RNA (siRNA), respectively, basal and LPS-induced proinflammatory gene expression was attenuated. Furthermore, macrophage G6PD increased activation of the p38 mitogen-activated protein kinase (MAPK) and NF-κB pathways, which may lead to a vicious cycle of oxidative stress and proinflammatory cascade. Together, these data suggest that an abnormal increase of G6PD in macrophages promotes oxidative stress and inflammatory responses in the adipose tissue of obese animals.

Original languageEnglish (US)
Pages (from-to)2425-2435
Number of pages11
JournalMolecular and cellular biology
Volume33
Issue number12
DOIs
StatePublished - Jun 1 2013

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ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

Cite this

Ham, M., Lee, J. W., Choi, A. H., Jang, H., Choi, G., Park, J., Kozuka, C., Sears, D. D., Masuzaki, H., & Kima, J. B. (2013). Macrophage glucose-6-phosphate dehydrogenase stimulates proinflammatory responses with oxidative stress. Molecular and cellular biology, 33(12), 2425-2435. https://doi.org/10.1128/MCB.01260-12