Effects of hypoxia on adipose tissue expression of NFκB, IκBα, IKKγ and IKAP in patients with chronic obstructive pulmonary disease

Cell Biochem Biophys. 2013 May;66(1):7-12. doi: 10.1007/s12013-012-9391-9.

Abstract

Recently we observed increased adipose tissue (AT) expression of CD40-related signaling proteins but no activation of tumor necrosis factor-α or CD68 in patients with chronic sustained hypoxia resulting from chronic obstructive pulmonary disease (COPD). Transcription factor nuclear factor-κB (NFκB) is involved in cellular responses to hypoxia and activates the proinflammatory gene expression with concomitant upregulation of its own repressors--inhibitors of κB (IκB) in an auto feedback loop. Inhibitor of kappaB kinase (IKK)-γ and inhibitor of kappaB kinase complex-associated protein (IKAP) are further regulatory proteins involved in NFκB signaling. In this study, we hypothesized that chronic sustained hypoxia significantly relates to IκBα, IKKγ and IKAP within the AT in COPD patients. In 20 patients with stable disease, samples of subcutaneous AT were analyzed using real-time PCR. Although no significant differences were observed between two groups categorized by median PaO2 in NFκB (p = 0.065), gene expressions of IκBα, IKKγ and IKAP were all higher in hypoxemic patients (p = 0.033; p = 0.050; p = 0.010, respectively). In multivariate analyses, PaO2 independently predicted AT IκBα, IKKγ and IKAP (R (2) = 0.490, p = 0.012; R (2) = 0.586, p = 0.002; R (2) = 0.504, p = 0.009, respectively). In conclusion, our data suggest significant AT upregulation of IκBα, IKKγ and IKAP by chronic sustained hypoxia in COPD patients.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Arterial Pressure
  • Biomarkers / metabolism
  • Body Mass Index
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Female
  • Gene Expression Regulation
  • Humans
  • Hypoxia / metabolism
  • Hypoxia / pathology*
  • I-kappa B Kinase / genetics
  • I-kappa B Kinase / metabolism*
  • I-kappa B Proteins / genetics
  • I-kappa B Proteins / metabolism*
  • Inflammation / metabolism
  • Inflammation / pathology
  • Male
  • Middle Aged
  • NF-KappaB Inhibitor alpha
  • NF-kappa B p50 Subunit / antagonists & inhibitors
  • NF-kappa B p50 Subunit / genetics
  • NF-kappa B p50 Subunit / metabolism
  • Oxygen / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / pathology
  • Transcriptional Elongation Factors

Substances

  • Biomarkers
  • Carrier Proteins
  • Elp1 protein, human
  • I-kappa B Proteins
  • IKBKG protein, human
  • NF-kappa B p50 Subunit
  • NFKB1 protein, human
  • NFKBIA protein, human
  • Transcriptional Elongation Factors
  • NF-KappaB Inhibitor alpha
  • I-kappa B Kinase
  • Oxygen