Protease nexin-1 activity in cultured Schwann cells

Mulligan, L.P.; Rosenblatt, Dorrie E.; Toms, R.; Johnson, David

doi:10.1016/0304-3940(91)90756-j

Cited by 11 publications

(6 citation statements)

References 23 publications

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“…Several proteins were previously shown to increase neurite growth [e.g., SPARC (24)(25)(26), meteorin (27,28), pleiotrophin (29), and glial cell line-derived neurotrophic factor family receptor a-1 (30)]. Other proteins are directly involved in regeneration [e.g., protease nexin-1 (glia-derived nexin) (31)(32)(33)(34)(35), galectin-1 (36), and ADAM proteins (37,38)]. Moreover, axon guidance cues were identified such as neural cell adhesion molecule 1, neuropilin1/2 and semaphorin 3A (39,40), secreted frizzled-related protein 1 (41), and furin (42).…”

Section: Composition Of Schwann Cell Secretomesmentioning

confidence: 99%

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

et al. 2018

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Schwann cells promote nerve regeneration by adaptation of a regenerative phenotype referred to as repair mediating Schwann cell. Down‐regulation of myelin proteins, myelin clearance, formation of Bungner's bands, and secretion of trophic factors characterize this cell type. We have previously shown that the sphingosine‐1‐phosphate receptor agonist Fingolimod/FTY720P promotes the generation of this particular Schwann cell phenotype by activation of dedifferentiation markers and concomitant release of trophic factors resulting in enhanced neurite growth of dorsal root ganglion neurons. Despite its biomedical relevance, a detailed characterization of the corresponding Schwann cell secretóme is lacking, and the impact of FTY720P on enhancing neurite growth is not defined. Here, we applied a label‐free quantitative mass spectrometry approach to characterize the secretomes derived from primary neonatal and adult rat Schwann cells in response to FTY720P. We identified a large proportion of secreted proteins with a high overlap between the neonatal and adult Schwann cells, which can be associated with biologic processes such as development, axon growth, and regeneration. Moreover, FTY720P‐treated Schwann cells release proteins downstream of Smad signaling known to support neurite growth. Our results therefore uncover a network of trophic factors involved in glial‐mediated repair of the peripheral nervous system.—Schira, J., Heinen, A., Poschmann, G., Ziegler, B., Hartung, H.‐P., Stühler, K., Küry, P. Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism. FASEB J. 33, 4703–4715 (2019). http://www.fasebj.org

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Section: Composition Of Schwann Cell Secretomesmentioning

confidence: 99%

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

et al. 2018

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“…Since previous studies showed that neurons contacting astrocytes are relatively resistant to Ca*+-mediated toxicity (Mattson and Rychlik, 1990) and because PN-1 is produced by astrocytes (Rosenblatt et al, 1987;Reinhard et al, 1988;Milligan et al, 1991;Reinhard et al, 1994), we examined Ca2+ responses to thrombin in neurons alone compared to neurons contacting astrocytes. To begin, we found rest levels of [Ca*+], to be 1.5-fold higher in neurons not contacting astrocytes as compared with neurons contacting astrocytes.…”

Section: Pn-1 Attenuates the Elevation Of [Ca2+] That Mediates Glucomentioning

confidence: 99%

Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury

et al. 1995

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Protease nexin-I (PN-1) is a 44 kDa serine proteinase inhibitor that rapidly inhibits thrombin by forming SDS stable complexes with serine at the catalytic site of the protease. Levels of both PN-1 and thrombin are increased in the brain in response to insults such as ischemia, suggesting roles in neural injury and repair processes. We now report that PN-1-protected cultured rat hippocampal neurons against glucose deprivation- induced damage (GDID), and the protection was abolished by equimolar thrombin. PN-1 reduced resting intracellular free calcium levels ([Ca2+]i) and attenuated the elevation of [Ca2+]i normally associated with GDID. Thrombin reduced neuronal survival and caused a significant increase in [Ca2+]i. Submaximally toxic levels of thrombin exacerbated GDID. Calcium responses to thrombin were attenuated in neurons contacting PN-1 immunoreactive astrocytes. These findings suggest that PN-1 and thrombin play important roles in modulating neuronal calcium responses, and vulnerability, to metabolic/excitotoxic insults.

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“…The high molecular weight PNI immunoreactivity found in both control and injured nerves has not been previously noted (Meier et al, 1989). It is not clear whether this PNI band represents a complex with an unidentified target protease, other than thrombin, or is a dimer, as is sometimes seen with purified PNI preparations (Mulligan et al, 1991). It is reasonable to suggest that endogenous thrombin/PNI complexes, if preformed, might be cleared quickly by a receptor similar or identical to the a2-macroglobulin/low density lipoprotein receptor-related protein (Orth et al, 1992;Bu et al, 1994), limiting our ability to detect them.…”

Section: Discussionmentioning

confidence: 78%

Neural Thrombin and Protease Nexin I Kinetics After Murine Peripheral Nerve Injury

Smirnova

Jianxin

Citron

et al. 1996

Journal of Neurochemistry

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We addressed the balance between thrombin and its serpin protease nexin I (PNI) after sciatic nerve injury in the mouse. Prothrombin levels increased twofold 24 h after nerve crush, as measured by a specific chromogenic assay, and peaked at day 3. Thrombin activity also increased 2-4 days after injury in distal sciatic nerve segments. Nerve RNA analysis using reverse transcriptasepolymerase chain reaction (RT-PCR) assay confirmed that prothrombin was synthesized locally. We also monitored PNI levels in these injured nerve samples by complex formation with an 125l-labeled target protease and found peak activity occurring later, 6-9 days after the thrombin induction. These data indicate that nerve injury first induces the synthesis of prothrombin, which is subsequently converted to active thrombin. Nerve crushinduced thrombin is followed by the generation of functionally active PNI and may be directly responsible for its induction. By immunocytochemistry with anti-PNI antibody, we found that activated Schwann cells were the source of induced PNI. These results support the concept that the balance between serine proteases and their serpins is dysregulated during nerve injury and suggests a role for its reestablishment in nerve damage repair. Key Words: Thrombin-Protease nexin 1-Protease/inhibitor balance-Nerve injury-Regeneration-Serpin.

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Protease nexin-1 activity in cultured Schwann cells

Cited by 11 publications

References 23 publications

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

Secretome analysis of nerve repair mediating Schwann cells reveals Smad‐dependent trophism

Protease nexin-1 and thrombin modulate neuronal Ca2+ homeostasis and sensitivity to glucose deprivation-induced injury

Neural Thrombin and Protease Nexin I Kinetics After Murine Peripheral Nerve Injury

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