Neutrophil gelatinase-associated lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2

Cell Stress Chaperones. 2010 Jul;15(4):395-403. doi: 10.1007/s12192-009-0154-5. Epub 2009 Nov 11.

Abstract

Lipocalin-2 (Lcn2, NGAL) is a member of the lipocalin super family with diverse function such as the induction of apoptosis, the suppression of bacterial growth, and modulation of inflammatory response. Much interest has recently been focused on the physiological/pathological role of the lipocalin-2 that is considered to be a novel protective factor against oxidative stress. However, its precise biological roles in this protection are not fully understood. In this report we intended to test the effect of lipocalin-2 on the expression of heme oxygenase ((1, 2)) and superoxide dismutase ((1, 2)) which are two strong antioxidants. NGAL was cloned to pcDNA3.1 plasmid by using genetic engineering method. The recombinant vector was transfected to CHO and HEK293T to establish stable cell expressing NGAL and the expression of HO-1, 2 and SOD(1, 2) were compared with appropriate controls by RT-PCR and western blot. On the other hand, expression of NGAL was suppressed by siRNA transfection in order to study the effect of lipocalin-2 on mentioned genes/proteins. The results showed that the expression of HO-1 and SOD(1, 2) enzymes were higher in cells expressing recombinant lipocalin-2 compared with the control cells. Although the expression of HO-1 was lower in NGAL silencing cells, the expression of SOD(1) and SOD(2) were higher. Our data suggest that NGAL is a potent inducer of HO-1 and somewhat SOD(1) and SOD(2) and it appears that part of antioxidant property of NGAL could be attributed to the induction of HO-1 and SOD(1, 2).

MeSH terms

  • Acute-Phase Proteins / genetics
  • Acute-Phase Proteins / metabolism*
  • Animals
  • CHO Cells
  • Cell Line
  • Cricetinae
  • Cricetulus
  • Heme Oxygenase-1 / metabolism*
  • Humans
  • Lipocalin-2
  • Lipocalins / genetics
  • Lipocalins / metabolism*
  • Oxidative Stress
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / metabolism*
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Superoxide Dismutase / metabolism*
  • Superoxide Dismutase-1
  • Transfection

Substances

  • Acute-Phase Proteins
  • LCN2 protein, human
  • Lipocalin-2
  • Lipocalins
  • Proto-Oncogene Proteins
  • RNA, Small Interfering
  • SOD1 protein, human
  • Heme Oxygenase-1
  • Superoxide Dismutase
  • Superoxide Dismutase-1
  • superoxide dismutase 2