Neutrophil gelatinase-associated lipocalin: a new antioxidant that exerts its cytoprotective effect independent on Heme Oxygenase-1

Free Radic Res. 2011 Jul;45(7):810-9. doi: 10.3109/10715762.2011.581279. Epub 2011 May 5.

Abstract

Neutrophil Gelatinase-Associated Lipocalin (NGAL/Lcn2), a member of the lipocalin family, has a variety of functions. There are extensive studies examining the expression of NGAL under harmful conditions. However, its precise function remains poorly understood. Heme Oxygenase 1 (HO-1) is an enzyme with well-established cytoprotective effects. Previous work showed that NGAL induces expression of HO-1. Interestingly, the same stimuli induced the expression of both NGAL and HO-1. The current study was designed to (1) determine whether NGAL exerts its cytoprotective effect through HO-1 and (2) compare NGAL and HO-1 with each other in terms of their protective role against oxidative stress. The current data indicate that NGAL exerts its cytoprotective effect independent of HO-1 and protects cells against oxidative stress more efficiently than HO-1. The data also strongly suggest that induction of NGAL under harmful conditions is a compensatory response to ameliorate oxidative stress-mediated toxicity. These findings may suggest new applications of NGAL, particularly when oxidative stress is a major factor.

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Antioxidants / metabolism*
  • Apoptosis
  • Cell Line, Tumor
  • Cytoprotection*
  • Gene Silencing
  • HEK293 Cells
  • Heme Oxygenase-1 / antagonists & inhibitors
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • In Situ Nick-End Labeling
  • Lipocalin-2
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Oxidative Stress
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • Protoporphyrins / pharmacology
  • RNA, Small Interfering

Substances

  • Acute-Phase Proteins
  • Antioxidants
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • Protoporphyrins
  • RNA, Small Interfering
  • zinc protoporphyrin
  • HMOX1 protein, human
  • Heme Oxygenase-1