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Kallikrein cascades in traumatic spinal cord injury

Title: Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration.
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Name(s): Radulovic, Maja, author
Yoon, Hyesook, author
Larson, Nadya, author
Wu, Jianmin, author
Linbo, Rachel, author
Burda, Joshua E, author
Diamandis, Eleftherios P, author
Blaber, Sachiko I, author
Blaber, Michael, author
Fehlings, Michael G, author
Scarisbrick, Isobel A, author
Type of Resource: text
Genre: Journal Article
Text
Date Issued: 2013-11-01
Physical Form: computer
online resource
Extent: 1 online resource
Language(s): English
Abstract/Description: Kallikreins (KLKs) are a family of 15 secreted serine proteases with emerging roles in neurologic diseases. To illuminate their contributions to the pathophysiology of spinal cord injury (SCI), we evaluated acute through chronic changes in the immunohistochemical appearance of 6 KLKs (KLK1, KLK5, KLK6, KLK7, KLK8, and KLK9) in postmortem human traumatic SCI cases, quantified their RNA expression levels in experimental murine SCI, and assessed the impact of recombinant forms of each enzyme toward murine cortical neurons in vitro. Temporally and spatially distinct changes in KLK expression were observed with partially overlapping patterns between human and murine SCI, including peak elevations (or reductions) during the acute and subacute periods. Kallikrein 9 showed the most marked changes and remained chronically elevated. Importantly, a subset of KLKs (KLK1, KLK5, KLK6, KLK7, and KLK9) were neurotoxic toward primary neurons in vitro. Kallikrein immunoreactivity was also observed in association with swollen axons and retraction bulbs in the human SCI cases examined. Together, these findings demonstrate that elevated levels of a significant subset of KLKs are positioned to contribute to neurodegenerative changes in cases of CNS trauma and disease and, therefore, represent new potential targets for the development of neuroprotective strategies.
Identifier: FSU_pmch_24128681 (IID), 10.1097/NEN.0000000000000007 (DOI), PMC4097185 (PMCID), 24128681 (RID), 24128681 (EID)
Grant Number: P30 CA015083, R01 NS052741, CA1060A11, R01NS052741
Publication Note: This NIH-funded author manuscript originally appeared in PubMed Central at https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4097185.
Subject(s): Adolescent
Adult
Aged
Animals
Axons/metabolism
Axons/pathology
Child
Child, Preschool
Female
Humans
Kallikreins/genetics
Kallikreins/metabolism
Male
Mice
Middle Aged
Nerve Degeneration/genetics
Nerve Degeneration/metabolism
Nerve Degeneration/pathology
Signal Transduction/physiology
Spinal Cord/metabolism
Spinal Cord/pathology
Spinal Cord Injuries/genetics
Spinal Cord Injuries/metabolism
Spinal Cord Injuries/pathology
Persistent Link to This Record: http://purl.flvc.org/fsu/fd/FSU_pmch_24128681
Owner Institution: FSU
Is Part Of: Journal of neuropathology and experimental neurology.
1554-6578
Issue: iss. 11, vol. 72

Choose the citation style.
Radulovic, M., Yoon, H., Larson, N., Wu, J., Linbo, R., Burda, J. E., … Scarisbrick, I. A. (2013). Kallikrein cascades in traumatic spinal cord injury: in vitro evidence for roles in axonopathy and neuron degeneration. Journal Of Neuropathology And Experimental Neurology. Retrieved from http://purl.flvc.org/fsu/fd/FSU_pmch_24128681