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Gene Review

Lcn2  -  lipocalin 2

Rattus norvegicus

Synonyms: Alpha-2-microglobulin-related protein, Alpha-2U globulin-related protein, Lipocalin-2, NGAL, Neutrophil gelatinase-associated lipocalin, ...
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Disease relevance of Lcn2

  • In rats without IT, the p35 levels slightly decreased after ischemia or reperfusion, whereas the levels of p25 (the truncated form of p35) were much higher than those in sham control rats after ischemia and remained elevated during reperfusion [1].

High impact information on Lcn2

  • Iron unloading depends on the cycling of 24p3/Ngal through acidic endosomes, but its pH sensitivity and its subcellular targeting differed from transferrin [2].
  • Indeed, during the conversion of mesenchyme into epithelia (where we discovered the protein), 24p3/Ngal and transferrin were endocytosed by different cells that characterize different stages of development, and they triggered unique responses [2].
  • In a previous study (H. Shirataki, K. Kaibuchi, T. Yamaguchi, K. Wada, H. Horiuchi, and Y. Takai, J. Biol. Chem. 267:10946-10949, 1992), we highly purified from bovine brain crude membranes the putative target protein for smg p25A/rab3A p25, a ras p21-related small GTP-binding protein implicated in neurotransmitter release [3].
  • These results indicate that rabphilin-3A is a novel protein that has C2 domains and selectively interacts with the GTP-bound form of rab3A p25 [3].
  • However, little is known about induction of NGAL expression in blood vessels [4].

Biological context of Lcn2

  • Neutrophil gelatinase-associated lipocalin (NGAL) has recently emerged as an important modulator of cell homeostasis [4].
  • Developmental expression and cellular localization of a novel brain-specific 25-kDa protein (p25), a substrate of tau protein kinase II, were investigated in the rat brain using polyclonal antibodies raised against peptides synthesized based on the p25 amino acid sequence [5].
  • Induction of the alpha 2MRP gene expression occurred within 24 h after addition of AGE [6].

Anatomical context of Lcn2

  • Elevated plasma NGAL levels, possibly because of activation of blood leukocytes, are associated with atherosclerosis [4].
  • Expression of NGAL mRNA and protein was also up-regulated in an NF-kappaB-dependent manner in rat and human vascular smooth muscle cells (SMCs) in response to interleukin-1beta stimulation [4].
  • Using a rat carotid artery injury model, we found that NGAL was highly induced in the intima after angioplasty but was attenuated by adenovirus-mediated expression of a dominant-negative mutant of inhibitor of nuclear factor (NF)-kappaB kinase beta (dnIKKbeta) [4].
  • Rat SMC-produced NGAL was present as mono- and homomeric forms in the cytosol and in a complex containing matrix metalloproteinase-9 (MMP-9) after secretion [4].
  • A brain-specific protein p25 is localized and associated with oligodendrocytes, neuropil, and fiber-like structures of the CA3 hippocampal region in the rat brain [5].

Associations of Lcn2 with chemical compounds


Analytical, diagnostic and therapeutic context of Lcn2

  • Although IT did not promote significant changes in p35 and p25 levels, it induced a slight increase in calpastatin and eIF4G levels in the hippocampal subregions after 4 h of reperfusion [1].
  • By western immunoblotting, p25 was found to be expressed only slightly in the embryonic period; the expression increased from 11 days up to 5 weeks of age, and continued to increase gradually until 1-2 years of age [5].


  1. Calpain-induced Proteolysis After Transient Global Cerebral Ischemia and Ischemic Tolerance in a Rat Model. Garc??a-Bonilla, L., Burda, J., Pi??eiro, D., Ayuso, I., G??mez-Calcerrada, M., Salinas, M. Neurochem. Res. (2006) [Pubmed]
  2. An iron delivery pathway mediated by a lipocalin. Yang, J., Goetz, D., Li, J.Y., Wang, W., Mori, K., Setlik, D., Du, T., Erdjument-Bromage, H., Tempst, P., Strong, R., Barasch, J. Mol. Cell (2002) [Pubmed]
  3. Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin. Shirataki, H., Kaibuchi, K., Sakoda, T., Kishida, S., Yamaguchi, T., Wada, K., Miyazaki, M., Takai, Y. Mol. Cell. Biol. (1993) [Pubmed]
  4. Induction of Neutrophil Gelatinase-Associated Lipocalin in Vascular Injury via Activation of Nuclear Factor-{kappa}B. Bu, D.X., Hemdahl, A.L., Gabrielsen, A., Fuxe, J., Zhu, C., Eriksson, P., Yan, Z.Q. Am. J. Pathol. (2006) [Pubmed]
  5. A brain-specific protein p25 is localized and associated with oligodendrocytes, neuropil, and fiber-like structures of the CA3 hippocampal region in the rat brain. Takahashi, M., Tomizawa, K., Fujita, S.C., Sato, K., Uchida, T., Imahori, K. J. Neurochem. (1993) [Pubmed]
  6. Isolation and characterization of the genes up-regulated in isolated neurons by aged garlic extract (AGE). Sumi , S., Tsuneyoshi, T., Matsuo, H., Yoshimatsu, T. J. Nutr. (2001) [Pubmed]
  7. Gene expression changes in the immature rat uterus: effects of uterotrophic and sub-uterotrophic doses of bisphenol A. Ashby, J., Odum, J. Toxicol. Sci. (2004) [Pubmed]
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