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 and Kabogo, Doreen and 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. ISSN 0002-9440

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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 Article
Journal or Publication Title: American Journal of Pathology
Uncontrolled Keywords: /dk/atira/pure/subjectarea/asjc/2700/2734
Subjects:
Departments: Faculty of Health and Medicine > Biomedical & Life Sciences
ID Code: 137325
Deposited By: ep_importer_pure
Deposited On: 07 Oct 2019 08:20
Refereed?: Yes
Published?: Published
Last Modified: 01 Jan 2020 12:16
URI: https://eprints.lancs.ac.uk/id/eprint/137325

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