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Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal-lysosomal markers in surviving neurons after 192-IgG-saporin administrations into the adult rat brain

Hawkes, Cheryl; Kabogo, Doreen; Amritraj, Asha and Kar, Satyabrata (2006). Up-regulation of cation-independent mannose 6-phosphate receptor and endosomal-lysosomal markers in surviving neurons after 192-IgG-saporin administrations into the adult rat brain. American Journal of Pathology, 169(4) pp. 1140–1154.

DOI (Digital Object Identifier) Link: https://doi.org/10.2353/ajpath.2006.051208
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Abstract

The cation-independent mannose 6-phosphate receptor (CI-MPR) is a single transmembrane domain glycoprotein that plays a major role in the trafficking of lysosomal enzymes from the trans-Golgi network to the endosomal-lysosomal (EL) system. Because dysfunction of EL system is associated with a variety of neurodegenerative disorders, it is possible that the CI-MPR may have a role in regulating neuronal viability after toxicity/injury. In the present study, we report that 192-IgG-saporin-induced loss of basal forebrain cholinergic neurons causes a transient upregulation of CI-MPR protein levels in surviving neurons of the basal forebrain and frontal cortex but not in the brainstem region, which was relatively spared by the immunotoxin. This was accompanied by a parallel time-dependent increase in other EL markers, ie, cathepsin D, Rab5, and LAMP2 in the basal forebrain region, whereas in the frontal cortex the levels of cathepsin D, and to some extent Rab5, were increased. Given the critical role of the EL system in the clearance of abnormal proteins in response to changing conditions, it is likely that the observed increase in the CI-MPR and components of the EL system in surviving neurons after 192-IgG-saporin treatment represents an adaptive mechanism to restore the metabolic/structural abnormalities induced by the loss of cholinergic neurons.

Item Type: Journal Item
Copyright Holders: 2006 American Society for Investigative Pathology
ISSN: 1525-2191
Academic Unit/School: Faculty of Science, Technology, Engineering and Mathematics (STEM) > Life, Health and Chemical Sciences
Faculty of Science, Technology, Engineering and Mathematics (STEM)
Related URLs:
Item ID: 44105
Depositing User: Cheryl Hawkes
Date Deposited: 07 Sep 2015 08:35
Last Modified: 07 Dec 2018 10:34
URI: http://oro.open.ac.uk/id/eprint/44105
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