title: Association of human neuroglobin with cystatin C, a cysteine proteinase inhibitor.
abstract: Neuroglobin (Ngb) is a newly discovered globin that is expressed in vertebrate brain. It has been reported that Ngb levels increase in neurons in response to oxygen deprivation, and that Ngb protects neurons from hypoxia. However, the mechanism of this neuroprotection remains unclear. In the present study, we identified human cystatin C, a cysteine proteinase inhibitor, as an Ngb-binding protein by using a yeast two-hybrid system. Surface plasmon resonance experiments verified that Ngb binds to cystatin C dimers, not to the monomers. Because both intracellular cystatin C and the amyloidogenic variant of cystatin C form dimers, Ngb may modulate the intracellular transport (or secretion) of cystatin C to protect against neuronal death under conditions of oxidative stress and/or it may have a role in the development of neurodegenerative diseases.
authors.affiliation: Department of Molecular Engineering, Graduate School of Engineering, Kyoto University, Kyoto 615-8510, Japan. kei@wakasugi.mbox.media.kyoto-u.ac.jp
authors.forename: Keisuke
authors.initials: K
authors.lastname: Wakasugi
authors.forename: Tomomi
authors.initials: T
authors.lastname: Nakano
authors.forename: Isao
authors.initials: I
authors.lastname: Morishima
mesh_terms: D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D055316:Cystatin C; D015891:Cystatins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D015853:Cysteine Proteinase Inhibitors / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D019281:Dimerization; D015723:Gene Library; D005914:Globins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000078787:Neuroglobin; D018384:Oxidative Stress / Q000235:genetics; D011485:Protein Binding; D012441:Saccharomyces cerevisiae / Q000235:genetics; D020349:Surface Plasmon Resonance; D014170:Transformation, Genetic; D020798:Two-Hybrid System Techniques
chemical_list: C525030:CST3 protein, human; D055316:Cystatin C; D015891:Cystatins; D015853:Cysteine Proteinase Inhibitors; D009419:Nerve Tissue Proteins; D000078787:Neuroglobin; D005914:Globins