Oxidative Stress Induced Lipocalin 2 Gene Expression: Addressing its Expression under the Harmful Conditions

Abstract

Lipocalin 2 (Lcn2, NGAL) is a member of the lipocalin superfamily with diverse functions such as the transport of fatty acids and the induction of apoptosis. Previous reports indicated that expression of Lcn2 is induced under harmful conditions. However, the mechanisms of the induction of Lcn2 expression remain to be elucidated. In this report, we intended to identify the factor or factors that induce Lcn2 expression. Up-regulation of Lcn2 expression after X-ray exposure was detected in the heart, the kidney and especially in the liver. Primary culture of liver component cells revealed that this up-regulation in the liver was induced in hepatocytes. Up-regulation of Lcn2 expression was also detected in HepG2 cells after the administration of X-rays or H(2)O(2). Interestingly, up-regulation of Lcn2 expression after H(2)O(2) treatment was canceled by the addition of the anti-oxidants, dimethylsulfoxide or cysteamine. These results strongly suggest that Lcn2 expression is induced by reactive oxygen species. Therefore, Lcn2 could be a useful biomarker to identify oxidative stress both in vitro and in vivo.

Neutrophil Gelatinase-Associated Lipocalin induces the expression of heme oxygenase-1 and superoxide dismutase 1, 2

“…There are mounting evidence indicating that HO-1 gene expression is induced by stimulates that increase the cellular production of ROS, including heme, heavy metals, UV light, hydrogen peroxide, and lipopolysaccharide (Immenschuh and Ramadori 2000, Hayashi et al 2001, Bussolati et al 2004, Kikuchi et al 2005, Bach 2006). In previous studies, we have shown the protective role of NGAL against ROS (Roudkenar et al 2007, Roudkenar et al 2008a, Roudkenar et al 2008b and in this study we report that NGAL induces HO-1 expression. To support this hypothesis, Kiayoshi Mori et al found that ischemiareperfusion enhances the expression of HO-1.…”

“…Moreover, it has been reported that NGAL is induced in the mouse liver when exposed to alpha particles and X-rays (Roudkenar et al 2007). Also, it was shown that NGAL acts as a cytoprotective factor against H 2 O 2 and cisplatin toxicity (Roudkenar et al 2008a, Roudkenar et al 2008b.…”

“…While it has been reported that NGAL might protect cells from ROS (Roudkenar et al 2007, Roudkenar et al 2008a, Roudkenar et al 2008b), its precise biological roles in this protection is not fully understood. Oxidative damage to macromolecules (nucleic acids, proteins, carbohydrates, and lipids) is mediated by reactive oxygen species (ROS) of intracellular origin such as hydrogen peroxide, oxygen free radicals, singlet oxygen, hypochlorite anion, nitric oxide, and peroxynitrite anion (Lavrovsky et al 2000, Limón-Pacheco andGonsebatt 2009).…”

The relationship between circulating neutrophil gelatinase-associated lipocalin and early alteration of metabolic parameters is associated with dietary saturated fat intake in non-diabetic Korean women

“…In addition, the present study also shows a significant negative correlation between circulating NGAL and SOD activity, an antioxidant biomarker. Roudkenar et al reported that NGAL expression induced and upregulated by reactive oxygen species can be attenuated by anti-oxidants [36].…”

Neutrophil Gelatinase Associated Lipocalin: Structure, Function and Role in Human Pathogenesis

“…This suggests that neutrophils, the primary effectors of acute inflammatory response in the body, require NGAL to home in to the target organs (in this case the transplanted heart). The latter role is suggested from observations made in both Chinese hamster ovary (CHO) and human embryonic kidney (HEK) cells that an aberrant expression of 24p3/Ngal leads to a significant upregulation in the expression of the antioxidant enzymes superoxide dismutase (SOD) and heme oxygenase (HO) (Bahmani et al, 2010;Roudkenar et al, 2007;Roudkenar et al, 2008c;Roudkenar et al, 2008a;Roudkenar et al, 2008b). NGAL also appears to play a role in wound healing.…”