Neuronal expression of hippocampal cholinergic neurostimulating peptide (HCNP)-precursor mRNA in rat brain

Taiji, Mutsuo; Tohdoh, Naoki; Ojika, Kosei

doi:10.1002/(sici)1097-4547(19960801)45:3<202::aid-jnr2>3.0.co;2-h

Cited by 18 publications

(8 citation statements)

References 40 publications

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“…In rat medial septal nuclei, RKIP was found to enhance in vitro acetylcholine synthesis by up-regulating choline acetyltransferase and possibly stimulating cholinergic neuronal pathways [57][58][59][60].…”

Section: Rkip Biologymentioning

confidence: 96%

“…Although RKIP is expressed in multiple tissues of the rat, higher expression levels can be found in the testis, brain oligodendrocytes, Schwann cells, Purkinje cells of the cerebellum, and within cortical and hippocampal layers of the brain [48,[53][54][55][56][57]. In rat medial septal nuclei, RKIP was found to enhance in vitro acetylcholine synthesis by up-regulating choline acetyltransferase and possibly stimulating cholinergic neuronal pathways [57][58][59][60].…”

Section: Rkip Biologymentioning

confidence: 99%

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Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP)

Keller

2004

Anti-Cancer Drugs

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The metastatic cascade is a complicated process that involves many steps from gain of the metastatic phenotype in the primary tumor cells through establishment of macroscopic tumor at the distant target organ. A group of genes, termed metastasis suppressor genes (MSG), encode for proteins that inhibit various steps of the metastatic cascade. Accordingly, loss of MSG promotes the metastatic phenotype. Although several MSG have been identified, the mechanisms through which they enhance metastasis are not clearly defined. Gene array analysis of a low metastatic LNCaP prostate cancer cell line compared to its highly metastatic derivative C4-2B prostate cancer cell line revealed decreased expression of raf kinase inhibitor protein (RKIP) in the C4-2B cell line. RKIP blocks the activation of several signaling pathways including MEK, G-proteins and NFkappaB. Immunohistochemical analysis of prostate cancer primary tumors and metastases revealed that RKIP protein expression was decreased in metastases. Restoration of RKIP expression in the C4-2B cell line diminished metastasis in a murine model. These results demonstrate that RKIP is a MSG. Loss of RKIP enhanced both angiogenesis and vascular invasion, and protected against apoptosis. These findings suggest that targeting the RKIP pathway may diminish the metastatic cascade. However, challenges exist as to the best method to target RKIP expression. Restoration of RKIP expression in all cancer cells in vivo is challenging. A plausible strategy is to use small molecules that target proteins in signaling pathways that are dysregulated due to loss of RKIP.

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Section: Rkip Biologymentioning

confidence: 96%

Section: Rkip Biologymentioning

confidence: 99%

Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP)

Keller

2004

Anti-Cancer Drugs

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“…The function of PEBP1 and its cleavage product, HCNP in Alzheimer's disease, and dementia is still unclear. Some studies confirm the accumulation of HCNP (Taiji and Ojika 1996), whereas others show decreased PEBP mRNA and protein expression (Maki et al 2002) which was correlated with increased amyloid beta plaques. Downregulation of PEBP1 may result in lower levels of HCNP or altered coordination of signal transduction pathways that may contribute to neuronal dysfunction and pathogenesis in AD (Odabaei et al 2004).…”

Section: Discussionmentioning

confidence: 94%

Downregulation of PEBP1 in Rat Brain Cortex in Hypoxia

et al. 2009

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In order to understand dementia and other ailments associated with high altitude hypoxia, adult Sprague Dawley male rats were exposed to simulated conditions of high altitude (7,500 m above sea level, 59 mmHg) for a period of 5 days and analyzed for changes in neuronal proteome by 2-D sodium dodecyl sulfate polyacrylamide gel electrophoresis. Protein extracts obtained from the brain cortex and hippocampus of the hypoxic rats were separated by 2-D gel electrophoresis. Differentially expressed proteins (analysis by 2-D gel analysis software, Bio-2D, Vilber-Lourmat, France and Delta2d, Decodon, Germany) were subjected to matrix-assisted laser desorption/ionization time-of-flight analysis. Among the proteins identified, the spot corresponding to pI 5.4 and molecular weight 21 kDa, identified as phosphatidylethanolamine binding protein (PEBP1), was consistently lowered (54%) in hypoxic cortex samples. PEBP1, also known as Raf kinase inhibitor protein, is a precursor of hippocampus cholinergic neurostimulatory peptide (HCNP). Western blot analysis revealed elevated phospho-extracellular signal-regulated kinase in hypoxic rat cortex samples, indicating activation of Raf/mitogen-activated protein kinase pathway under hypoxia. Lowered HCNP levels leading to 23% decrease in choline acetyltransferase and 63% increase in acetylcholinesterase activity were detected in hypoxic rat brain cortex, while no significant change was noted in hippocampus. Since PEBP1 is lowered in a number of neurological disorders associated with dementia, we speculate that lowered expression of PEBP1 might be responsible for dementia associated with high-altitude hypoxia. Further studies targeting PEBP1 might give clues about signaling pathways associated with hypoxia and dementia.

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“…The speciftc accumulation of HCNP-related components in hippocampal Hirano bodies suggests that these molecules may be directly involved in the formation of abnormal microfilaments [2, 31, the main components of Hirano bodies. Support for this notion is provided by recent observations that the highest levels of HCNP precursor protein mRNA expression [18] and HCNP immunoreactivity are seen in pyramidal neurons of the hippocampus of rats [8, 111. However, the elucidation of the actual role of HCNP-reIated components in the mechanisms involved in Hiran0 body formation requires additional investigations.…”

Section: Discussionmentioning

confidence: 98%

Possible implication of hippocampal cholinergic neurostimulating peptide (HCNP)‐related components in Hirano body formation

Mitake

Katada

Otsuka

et al. 1996

Neuropathology Appl Neurobio

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We have previously demonstrated that hippocampal cholinergic neurostimulating peptide (HCNP)-related components accumulate in almost all Hirano bodies in Sommer's sector of the hippocampus of elderly individuals, and that the number of HCNP-positive Hirano bodies is greater in patients with Alzheimer's disease. Although Hirano bodies occur preferentially in the neuronal processes of the stratum pyramidale of the hippocampus, they can be seen occasionally as small inclusions, intermingled with neurofibrillary tangles and in association with senile plaques. Here we show that the small inclusions are also recognized by an anti-HCNP antibody, and by using immunoelectron microscopy demonstrate that these HCNP-positive inclusions, intermingled with tau protein-positive neurofibrillary tangles and beta-amyloid-positive senile plaques are indeed Hirano bodies. These findings strongly suggest that HCNP-related components may be involved in Hirano body formation.

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Neuronal expression of hippocampal cholinergic neurostimulating peptide (HCNP)-precursor mRNA in rat brain

Cited by 18 publications

References 40 publications

Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP)

Metastasis suppressor genes: a role for raf kinase inhibitor protein (RKIP)

Downregulation of PEBP1 in Rat Brain Cortex in Hypoxia

Possible implication of hippocampal cholinergic neurostimulating peptide (HCNP)‐related components in Hirano body formation

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