Angiostrongylus cantonensis infection induces MMP-9 and causes tight junction protein disruption associated with Purkinj
- PDF / 4,822,041 Bytes
- 9 Pages / 595.276 x 790.866 pts Page_size
- 58 Downloads / 146 Views
HELMINTHOLOGY - ORIGINAL PAPER
Angiostrongylus cantonensis infection induces MMP-9 and causes tight junction protein disruption associated with Purkinje cell degeneration Shih-Chan Lai 1 & Cheng-You Lu 2 & Ling-Yuh Shyu 1 & Ke-Min Chen 1 Received: 15 January 2020 / Accepted: 2 August 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Angiostrongylus cantonensis causes a human central nervous system (CNS) infection characterized by eosinophilic meningitis or meningoencephalitis. Individuals infected with A. cantonensis exhibit unbalanced walking. The mechanism of extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. Tight junction proteins (e.g., claudin-5 and zonula occludens-1) are the most important regulators of paracellular permeability and cellular adhesion. In a previous study, we found that increased matrix metalloproteinase-9 (MMP-9) activity may be associated with blood–CNS barrier disruption and/or the degeneration of Purkinje cells in eosinophilic meningitis caused by A. cantonensis. In the present study, the co-localization of MMP-9 and tight junction proteins on the degeneration of Purkinje cells was measured via confocal laser scanning immunofluorescence microscopy. The statistical evidence indicated that MMP-9 correlated between tight junction protein disruption and Purkinje cell degeneration at 20 days post-infection with A. cantonensis. In conclusion, Purkinje cell degeneration is highly correlated with tight junction protein disruption via the MMP-9 activation pathway. Keywords Purkinje cell . MMP-9 . Angiostrongylus cantonensis
Introduction Angiostrongylus cantonensis is a visible neurotropic nematode that lives and grows in the central nervous system (CNS) of its mammalian hosts (Nishimura and Hung 1997). A. cantonensis infection induces severe CNS diseases, especially eosinophilic meningitis (Hsu et al. 1990) or meningoencephalitis (Gardiner et al. 1990). Neurological disorders and mechanical damage are caused by worms migrating in an A. cantonensis–infected nonpermissive host brain (Yoshimura et al. 1994) and the neurotoxicity of eosinophilderived basic proteins, serine proteases, and matrix Section Editor: David Bruce Conn * Ke-Min Chen [email protected] 1
Department of Parasitology, School of Medicine, Chung Shan Medical University, 110, Section 1, Chien-Kuo North Road, Taichung 402, Taiwan
2
Cardiovascular and Mitochondrial Related Disease Research Center, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien 970, Taiwan
metalloproteinases (MMPs) (Durack et al. 1979; Fredens et al. 1982; Hou et al. 2004; Lee et al. 2004). MMPs are a family of zinc-binding endopeptidases that catalyze the disruption of various extracellular matrices (ECMs) (Nagase and Woessner 1999). MMP-9 exhibits proteolytic activity against numerous ECM components (Sternlicht and Werb 2001). A mature CNS normally contains non-detectable or low levels of most MMPs, but an increased MMP expression has also been reported in various neuropath
Data Loading...
