Injury induces neuropsin mRNA in the central nervous system

Tomizawa, Kaori; He, Xiang; Yamanaka, Hiroki; Shiosaka, Sadao; Yoshida, Shigetaka

doi:10.1016/s0006-8993(99)01238-x

Cited by 21 publications

(25 citation statements)

References 16 publications

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“…Consistent with previous studies, the expression of neuropsin mRNA in WT mice was increased in the white matter of the spinal cord after injury (Tomizawa et al, 1999;Terayama et al, 2004). Extending on previous results, our findings demonstrate that neuropsin may promote oligodendrocyte death, demyelination and axonal degeneration after SCI.…”

Section: Discussionsupporting

confidence: 92%

“…Oligodendrocytes are highly vulnerable to excitotoxic signals mediated by glutamate receptors of the AMPA and kainate classes compared to astrocytes (Oka et al, 1993;Yoshioka et al, 1996;Agrawal and Fehlings, 1997;Matute -27 -et al, 1997;McDonald et al, 1998). Our previous experiments showed that excitotoxic injury caused by injection of kainate into the CNS induced expression of neuropsin mRNA in oligodendrocytes (Tomizawa et al, 1999). Furthermore, it has been shown that the proteolytic activation of neuropsin is induced in a glutamate receptor-dependent manner .…”

Section: Discussionmentioning

confidence: 96%

“…It has been reported that the expression of neuropsin is induced in several pathological conditions in the CNS including excitotoxic, traumatic or immunological injury, seizure and Alzheimer's disease (Okabe et al, 1996;Tomizawa et al, 1999;He et al, 2001;Shimizu-Okabe et al, 2001;Terayama et al, 2004;Terayama et al, 2005a). …”

Section: Discussionmentioning

confidence: 99%

“…A biochemical analysis of recombinant and native neuropsin suggested that it is an extracellular trypsin-type protease with a relatively narrow spectrum of substrates (Shimizu et al, 1998). Our previous experiments showed that traumatic, excitotoxic and immunological injury induced expression of neuropsin mRNA in the area surrounding the lesion in the CNS (Tomizawa et al, 1999;Terayama et al, 2004;Terayama et al, 2005a). Combined in situ hybridization and immunohistochemistry revealed that most of the cells expressing neuropsin mRNA were mature oligodendrocytes (Terayama et al, 2004).…”

Section: Introductionmentioning

confidence: 95%

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Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

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Abbreviations: SCI, spinal cord injury; DIG, digoxigenin; APC, adenomatus polyposis coli; MBP, myelin basic protein; TUNEL, TdT-mediated dUTP-fluorescein nick end labeling -3 - AbstractPrevious studies indicated that the expression of neuropsin, a serine protease, is induced in mature oligodendrocytes after injury to the central nervous system (CNS). The pathophysiology of spinal cord injury (SCI) involves primary and secondary mechanisms, the latter contributing further to permanent losses of function. To explore the role of neuropsin after SCI, histochemical and behavioral analyses were performed in wild-type (WT) and neuropsin-deficient (neuropsin -/-) mice using a crush injury model, a well-characterized and consistently reproducible model of SCI. In situ hybridization revealed that neuropsin mRNA expression was induced in the spinal cord white matter from WT mice after crush SCI, peaking at day 4. Neuropsin -/-mice showed attenuated demyelination, oligodendrocyte death, and axonal damage after SCI.Although axonal degeneration in the corticospinal tract was obvious caudal to the lesion site in both strains of mice after SCI, the number of surviving nerve fibers caudal to the lesion was significantly larger in neuropsin -/-mice than WT mice. Behavioral analysis revealed that the recovery at days 10-42 was significantly improved in neuropsin -/-mice compared to WT mice in spite of the severe initial hindlimb impairments due to SCI in both strains. These observations suggest that neuropsin is involved in the secondary phase of the pathogenesis of SCI mediated by demyelination, oligodendrocyte death, and axonal degeneration.-4 -

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Section: Discussionsupporting

confidence: 92%

Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

et al. 2007

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“…Accordingly, hK6 has been implicated in the progression of Alzheimer's disease. This activity of hK6 in brain is consistent with the finding that its mRNA is induced in the perilesioned region upon injury of the central nervous system (39). These results and the fact that hK6 has been found in significantly increased concentrations in the serum of ovarian cancer patients and in the cerebrospinal fluid, plasma, and blood of Alzheimer's disease patients have led to the development of an immunofluorometric assay for the measurement of this new biomarker for breast and ovarian cancer and for Alzheimer's disease (40 -42).…”

supporting

confidence: 90%

The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family

Gomis‐Rüth¹,

Bayés²,

Sotiropoulou³

et al. 2002

Journal of Biological Chemistry

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Zyme/protease M/neurosin/human kallikrein 6 (hK6) is a member of the human kallikrein family of trypsinlike serine proteinases and was originally identified as being down-regulated in metastatic breast and ovarian tumors when compared with corresponding primary tumors. Recent evidence suggests that hK6 may serve as a circulating tumor marker in ovarian cancers. In addition, it was described in the brain of Parkinson's disease and Alzheimer's disease patients, where it is implicated in amyloid precursor protein processing. It is thus a biomarker for these diseases. To examine the mechanism of activation of hK6, we have solved the structure of its proform, the first of a human kallikrein family member. The proenzyme displays a fold that exhibits chimeric features between those of trypsinogen and other family members. It lacks the characteristic "kallikrein loop" and forms the six disulfide bridges of trypsin. Pro-hK6 displays a completely closed specificity pocket and a unique conformation of the regions involved in structural rearrangements upon proteolytic cleavage activation. This points to a novel activation mechanism, which could be extrapolated to other human kallikreins.

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2006

Dial. Transplant.

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We have analyzed surfactant protein B (SP‐B) and its encoding gene (SFTPB, MIM 178640) in 40 unrelated pediatric patients with unexplained respiratory distress (URD). There was high consanguinity (eight kindreds) and an underlying autosomal recessive trait could be inferred in most cases, with overall high sex ratio (32/17) suggesting proband's gender to impact on penetrance. The clinical/biological presentations fitted into three major nosologic frameworks. I: SP‐B deficiency (nine probands), complete or incomplete, with homozygous/compoundly heterozygous mutations identified (six probands), including one from the population isolate of Réunion Island (496delG). In addition, there was a consanguineous kindred in which incomplete deficiency was unambiguously unlinked to SFTPB. II: pulmonary alveolar proteinosis (PAP, 19 probands), with typical storage of PAS‐positive material within the alveoli with foamy macrophages and variable interstitial reaction, which was diagnosed in most patients from Réunion Island. In contrast to previously published findings, mutation and/or segregation analyses excluded SFTPB as a disease locus, although slight metabolic derangement related to SP‐B and/or mild SFTPB changes could somehow contribute to disease. III: URD without evidence for SP‐B deficiency or PAP (12 probands), equally unlinked to SFTPB, although a single patient had a possibly causal, maternally‐derived, heterozygous genetic change (G4521A). The population frequency of five known and four novel SNPs was studied, providing as many potential markers for pulmonary disease related to SFTPB. Overall, URD was found to be heterogeneous, both phenotypically and genetically, even in population isolates where a founder effect might have been expected. When disease loci are identified, patient genotyping will be crucial as a diagnostic aid, for devising proper treatment, and as a basis for genetic counseling. © 2003 Wiley‐Liss, Inc.

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Injury induces neuropsin mRNA in the central nervous system

Cited by 21 publications

References 16 publications

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

Neuropsin promotes oligodendrocyte death, demyelination and axonal degeneration after spinal cord injury

The Structure of Human Prokallikrein 6 Reveals a Novel Activation Mechanism for the Kallikrein Family

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