Peroxiredoxin V in multiple sclerosis lesions: predominant expression by astrocytes.
Oxidative stress is implicated in the pathogenesis of multiple sclerosis (MS). Defence against oxidative damage is mediated by antioxidants. Peroxiredoxin V (PRDX V) is an intracellular anti-oxidant enzyme with peroxynitrite reductase activity. It is increased during inflammation, when free radical production intensifies, and is protective in an animal model of brain injury. However, little is known about PRDX V expression in the human brain. We investigated PRDX V expression in white matter from normal human brain (n = 5) and MS patients (n = 18), using immunohistochemistry and immunoblotting. A global increase in PRDX V was evident in MS normal-appearing white matter (NAWM) but the most striking increase was in astrocytes in MS lesions. PRDX V- positive hypertrophic reactive astrocytes were seen in acute lesions where inflammation was present. Yet surprisingly, in chronic lesions (CL), where inflammation has abated and a glial scar formed, there was strong PRDX V staining of post-reactive, scar astrocytes. Furthermore, immunoblotting analysis of tissue from two MS cases confirmed a substantial increase in PRDX V expression in CL compared with NAWM from the same individual. This might indicate ongoing oxidative stress despite the absence of histologically defined inflammation. Further investigations of this phenomenon will be of interest for therapeutic targeting.
Holley
J E
JE
Institute of Biomedical and Clinical Science, Peninsula Medical School (Exeter), and Royal Devon and Exeter Hospital, Devon, UK. janet.holley@pms.ac.uk
Newcombe
J
J
Winyard
P G
PG
Gutowski
N J
NJ
D001253:Astrocytes / Q000473:pathology*; D001921:Brain / Q000166:cytology / Q000473:pathology; D002102:Cadaver; D005786:Gene Expression Regulation; D006801:Humans; D015151:Immunoblotting; D007150:Immunohistochemistry; D009103:Multiple Sclerosis / Q000473:pathology*; D054464:Peroxiredoxins / Q000378:metabolism*; D012016:Reference Values
C515974:PRDX5 protein, human; D054464:Peroxiredoxins