Lipocalin-2 (LCN2), also known as neutrophil gelatinase-associated lipocalin (NGAL), is a 25 kDa protein belonging to the lipocalin superfamily. It was initially found in activated neutrophils, however, many other cells, like kidney tubular cells, may produce NGAL in response to various insults. This protein is released from injured tubular cells after various damaging stimuli, is already known by nephrologists as one of the most promising biomarkers of incoming Acute Kidney Injury (AKI). Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions. Moreover, recent studies seem to suggest a potential involvement of this factor also in the genesis and progression of chronic kidney diseases. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores, which are high-affinity iron chelators. NGAL, first known as an antibacterial factor of natural immunity, and an acute phase protein, is currently one of the most interesting and enigmatic proteins involved in the process of tumor development. acting as an intracellular iron carrier and protecting MMP9 from proteolytic degradation, NGAL has a clear pro-tumoral effect. In thyroid carcinomas, NGAL is strongly induced by NF-kB, an important factor involved both in tumor growth and in the link between chronic inflammation and neoplastic development. Thus, Lipocalin-2 (LCN2/NGAL) has been implicated in a variety of processes including cell differentiation, proliferation, survival and morphogenesis.
Neutrophil gelatinase-associated lipocalin(LCN2) is a secreted protein and belongs to the calycin superfamily. This protein is released from injured tubular cells after various damaging stimuli; is already known by nephrologists as one of the most promising biomarkers of incoming Acute Kidney Injury (AKI). Recent evidence also suggests its role as a biomarker in a variety of other renal and non-renal conditions. Moreover; recent studies seem to suggest a potential involvement of this factor also in the genesis and progression of chronic kidney diseases. NGAL is the first known mammalian protein which specifically binds organic molecules called siderophores; which are high-affinity iron chelators. NGAL; first known as an antibacterial factor of natural immunity; and an acute phase protein; is currently one of the most interesting and enigmatic proteins involved in the process of tumor development. acting as an intracellular iron carrier and protecting MMP9 from proteolytic degradation; NGAL has a clear pro-tumoral effect; as has already been observed in different tumors (e.g. breast; stomach; oesophagus; brain) in humans. In thyroid carcinomas; NGAL is strongly induced by NF-kB; an important factor involved both in tumor growth and in the link between chronic inflammation and neoplastic development. Thus; Lipocalin-2 (LCN2/NGAL) has been implicated in a variety of processes including cell differentiation; proliferation; survival and morphogenesis.
LCN2 is iron-trafficking protein involved in multiple processes such as apoptosis; innate immunity and renal development. LCN2 binds iron through association with 2;5-dihydroxybenzoic acid (2;5-DHBA); a siderophore that shares structural similarities with bacterial enterobactin; and delivers or removes iron from the cell; depending on the context. LCN2 is involved in apoptosis due to interleukin-3 (IL3) deprivation: iron-loaded form increases intracellular iron concentration without promoting apoptosis; while iron-free form decreases intracellular iron levels; inducing expression of the proapoptotic protein BCL2L11/BIM; resulting in apoptosis. LCN2 is involved in innate immunity; possibly by sequestrating iron; leading to limit bacterial growth.
Human N-Glycosylase/DNA Lyase(OOG1) is a DNA repair enzyme, which belongs to the type-1 OGG1 family. OOG1 incises DNA at 8-oxoG residues, and excises 7,8-dihydro-8-oxoguanine and 2,6-diamino-4-hydroxy-5-N-methylformamidopyrimidine (FAPY) from damage DNA. It has a β-lyase activity that nicks DNA 3’ to the lesion. OOG1 together with APEX1 is recruited to nuclear speckles in UVA-irradiated cells. The OGG1 gene mutations may be caused Renal cell carcinoma.
Nogo-66 Receptor-Related Protein 3 (NgR3) has primary structures with NgR2 (NgRH1, NgRL3) and biochemical properties that are homologous to Nogo-66 receptor (NgR), and constitute a novel neuronal receptor protein family. NgR is GPI-anchored and contains eight leucine-rich repeats (LRR), it is the neuronal receptor for the myelin- associated proteins Nogo-A, OMgp (oligodendrocyte myelin glycoprotein), and MAG (myelin-associated glycoprotein) and mediates the inhibition of CNS axonal regeneration both in vitro and in vivo. NgR2 and NgR3 have similar structure and distinct but overlapping expression versus NgR. NgR2 can be metalloproteinase-cleaved to release a soluble ectodomain. NgR2 has also been shown to bind MAG, but ligands for NgR3 have not yet been determined. Mature huaman NgR3 shares 88%, 88%, 48% and 44% amino acid identity with mature mouse NgR3, rat NgR3, human NgRH1 and NgR, repectively.
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