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PMID:15140875

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Citation

Zhou, Z, Yamamoto, Y, Sugai, F, Yoshida, K, Kishima, Y, Sumi, H, Nakamura, H and Sakoda, S (2004) Hepatoma-derived growth factor is a neurotrophic factor harbored in the nucleus. J. Biol. Chem. 279:27320-6

Abstract

Hepatoma-derived growth factor (HDGF) is a heparin-binding proliferating factor originally isolated from conditioned medium of the hepatoma-derived cell line HuH-7. HDGF has greatest homology in an amino acid sequence with high mobility group 1 (HMG1), which has been characterized as a DNA-binding, inflammatory, and potent neurite outgrowth molecule. HDGF is reported to be widely expressed and act as a growth factor in many kinds of cells. However, it has not been investigated in the nervous system. Here, we show by Western blot analysis that HDGF is present in the mouse brain from the embryonic period until adulthood. In situ hybridization and immunohistochemical analyses revealed that HDGF was expressed mainly in neurons, and HDGF protein was localized to the nucleus. HDGF and high mobility group 1 were secreted under physiological conditions and released extracellularly in necrotic conditions. Furthermore, we showed that exogenously supplied HDGF had a neurotrophic effect and was able to partially prevent the cell death of neurons in which endogenous HDGF was suppressed. Therefore, we propose that HDGF is a novel type of neurotrophic factor, on account of its localization in the nucleus and its potential to function in an autocrine manner under both physiological and pathological conditions throughout life.

Links

PubMed Online version:10.1074/jbc.M308650200

Keywords

Animals; Apoptosis/physiology; Autocrine Communication; Cell Line, Tumor; Cell Nucleus/metabolism; Cell Survival/drug effects; Cell Survival/physiology; HMGA1a Protein/secretion; Hippocampus/cytology; Hippocampus/metabolism; Hippocampus/ultrastructure; Intercellular Signaling Peptides and Proteins/genetics; Intercellular Signaling Peptides and Proteins/pharmacology; Intercellular Signaling Peptides and Proteins/physiology; Intercellular Signaling Peptides and Proteins/secretion; Male; Mice; Mice, Inbred C57BL; Nerve Growth Factors/genetics; Nerve Growth Factors/pharmacology; Nerve Growth Factors/physiology; Nerve Growth Factors/secretion; Neurons/cytology; Neurons/drug effects; Neurons/metabolism; RNA, Messenger/biosynthesis

Significance

Annotations

Gene product Qualifier GO ID GO term name Evidence Code with/from Aspect Notes Status


See also

References

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