Purification and structural analysis of hippocampal cholinergic neurostimulating peptide

Ojika, Kosei; Kojima, Shinichi; Ueki, Yoshitaka; Fukushima, Nobuyuki; Hayashi, Ken’ichiro; Yamamoto, Masahiko

doi:10.1016/0006-8993(92)90465-l

Cited by 72 publications

(63 citation statements)

References 31 publications

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“…For instance, PEDF, 1 a serpin inhibitor with potent antiangiogenic activity (14), was detected as a protein secreted by preadipocytes but not by adipocytes. Conversely, we found an acute phase reactant, haptoglobin, and two smaller polypeptides, hippocampal cholinergic neurostimulating peptide (HCNP) and neutrophil gelatinase-associated lipocalin (NGAL), that were produced by adipocytes (15,16). We showed that whereas haptoglobin was correspondingly up-regulated at the mRNA level, NGAL and HCNP showed no change in mRNA expression levels suggesting that the regulation of these protein levels occurs post-transcriptionally.…”

mentioning

confidence: 99%

A Proteomic Approach for Identification of Secreted Proteins during the Differentiation of 3T3-L1 Preadipocytes to Adipocytes

Kratchmarova

Kalume

Blagoev

et al. 2002

Molecular & Cellular Proteomics

236

187

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We have undertaken a systematic proteomic approach to purify and identify secreted factors that are differentially expressed in preadipocytes versus adipocytes. Using one-dimensional gel electrophoresis combined with nanoelectrospray tandem mass spectrometry, proteins that were specifically secreted by 3T3-L1 preadipocytes or adipocytes were identified. In addition to a number of previously reported molecules that are up-or down-regulated during this differentiation process (adipsin, adipocyte complement-related protein 30 kDa, complement C3, and fibronectin), we identified four secreted molecules that have not been shown previously to be expressed differentially during the process of adipogenesis. Pigment epithelium-derived factor, a soluble molecule with potent antiangiogenic properties, was found to be highly secreted by preadipocytes but not adipocytes. Conversely, we found hippocampal cholinergic neurostimulating peptide, neutrophil gelatinase-associated lipocalin, and haptoglobin to be expressed highly by mature adipocytes. We also used liquid chromatography-based separation followed by automated tandem mass spectrometry to identify proteins secreted by mature adipocytes. Several additional secreted proteins including resistin, secreted acidic cysteine-rich glycoprotein/osteonectin, stromal cell-derived factor-1, cystatin C, gelsolin, and matrix metalloprotease-2 were identified by this method. To our knowledge, this is the first study to identify several novel secreted proteins by adipocytes by a proteomic approach using mass spectrometry. Molecular & Cellular Proteomics 1:213-222, 2002.

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mentioning

confidence: 99%

A Proteomic Approach for Identification of Secreted Proteins during the Differentiation of 3T3-L1 Preadipocytes to Adipocytes

Kratchmarova

Kalume

Blagoev

et al. 2002

Molecular & Cellular Proteomics

236

187

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“…However, PEBP1 can be also released into the extracellular environment by alternative secretion and act as a soluble factor (79). These functions are mediated by an N-terminal peptide, which is proteolytically removed from PEBP1 and that was named hippocampal cholinergic neurostimulating peptide (HCNP) because of its functions in neuronal differentiation and acetylcholine synthesis (80). HCNP also acts as an endocrine factor in cardiac physiology, demonstrating a role in nonneuronal organs (79,81).…”

Section: Discussionmentioning

confidence: 99%

Matrix Metalloproteinase 10 Degradomics in Keratinocytes and Epidermal Tissue Identifies Bioactive Substrates With Pleiotropic Functions*

Schlage

Kockmann

Sabino

et al. 2015

Molecular & Cellular Proteomics

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“…3 The original studies showed that HCNP stimulated the development and differentiation of cholinergic neurons in cultures of rat medial septal nuclei, by enhancing the activity of choline acetyltransferase (ChAT) and thus promoting acetylcholine synthesis. 3,46 These medial septal cholinergic neurons project back to the hippocampus to form the septohippocampal cholinergic pathway, whose dysfunction has been linked to cognitive impairments, particularly those associated with aging. 47 HCNP's ability to enhance ChAT expression specifically in the septal medial nucleus, and promote cholinergic phenotype development, was later confirmed in vivo using transgenic mice that overexpressed HCNP in the murine forebrain and hippocampus.…”

Section: Rkip Hcnp and Neural Developmentmentioning

confidence: 99%

“…Then, in 1992, Ojika et al purified a novel 11-residue peptide from the soluble fraction of neonatal rat hippocampi, and called it hip-pocampal cholinergic neurostimulating peptide (HCNP) because of its ability to stimulate acetylcholine synthesis in cultures of medial septal nuclei, a region of the brain that receives inputs from the hippocampus. 3 It would be another three years before the genes that encode rat and human HCNP were cloned, and recognized as homologs of bovine pebp1. 4 The discovery of HCNP was, in some respects, a major step toward ascribing a physiologic activity to this mysterious gene in the mammalian brain.…”

Section: Introduction: History Of Rkipmentioning

confidence: 99%

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

et al. 2014

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In 1984, a cytosolic protein was isolated from bovine brain and coined phosphatidylethanolamine binding protein (PEBP) to describe its phospholipid-binding potential. Its cellular function remained elusive for more than a decade until it was discovered that PEBP had the ability to suppress the Raf1-mitogen activated protein kinase (MAPK) pathway, earning it the new name of Raf1 kinase inhibitory protein (RKIP). This milestone discovery has paved the way for numerous studies that have now extended the reach of RKIP's function to other signaling cascades, within the context of various physiological and pathophysiological systems. This review will summarize our current knowledge of the neurophysiological roles of RKIP in the mammalian brain, including its function in the circadian clock and synaptic plasticity. It will also discuss evidence for an involvement of RKIP and its derived neuropeptide, hippocampal cholinergic neurostimulating peptide (HCNP), in neural development and differentiation. Implications in certain pathologies such as Alzheimer's disease and brain cancer will be highlighted. By chronicling the diverse functions of RKIP in the brain, we hope that this review will serve as a timely resource that ignites future studies on this versatile, multifaceted protein in the nervous system.

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Purification and structural analysis of hippocampal cholinergic neurostimulating peptide

Cited by 72 publications

References 31 publications

A Proteomic Approach for Identification of Secreted Proteins during the Differentiation of 3T3-L1 Preadipocytes to Adipocytes

A Proteomic Approach for Identification of Secreted Proteins during the Differentiation of 3T3-L1 Preadipocytes to Adipocytes

Matrix Metalloproteinase 10 Degradomics in Keratinocytes and Epidermal Tissue Identifies Bioactive Substrates With Pleiotropic Functions*

Raf Kinase Inhibitory Protein (RKIP): Functional Pleiotropy in the Mammalian Brain

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