Protective effects of peroxiredoxin-1 at the injured blood-brain barrier.
Reactive oxygen species (ROS) play a pivotal role in the development of neuroinflammatory disorders, such as multiple sclerosis (MS). Here, we studied the effect of ROS on protein expression in brain endothelial cells (BECs) using proteomic techniques and show that long-term exposure to ROS induces adaptive responses in BECs to counteract an oxidative attack. ROS induce differential protein expression in BECs, among which is peroxiredoxin-1 (Prx1). To further study the role of Prx1 we established a BEC line overexpressing Prx1. Our data indicate that Prx-1 overexpression protects BECs from ROS-induced cell death, reduces adhesion and subsequent transendothelial migration of monocytes by decreasing intercellular adhesion molecule-1 expression, and enhances the integrity of the BEC layer. Interestingly, vascular Prx1 immunoreactivity was markedly upregulated in inflammatory lesions of experimental autoimmune encephalomyelitis (EAE) animals and active demyelinating MS lesions. These findings indicate that enhanced vascular Prx1 expression may reflect the occurrence of vascular oxidative stress in EAE and MS. On the other hand, it may function as an endogenous defense mechanism to inhibit leukocyte infiltration and counteract ROS-induced cellular injury.
Schreibelt
Gerty
G
Department of Molecular Cell Biology and Immunology, VU University Medical Center, Amsterdam, The Netherlands.
van Horssen
Jack
J
Haseloff
Reiner F
RF
Reijerkerk
Arie
A
van der Pol
Susanne M A
SM
Nieuwenhuizen
Orm
O
Krause
Eberhard
E
Blasig
Ingolf E
IE
Dijkstra
Christine D
CD
Ronken
Eric
E
de Vries
Helga E
HE
D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism* / Q000473:pathology; D015153:Blotting, Western; D001921:Brain / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line; D002465:Cell Movement / Q000502:physiology; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism; D042783:Endothelial Cells / Q000378:metabolism*; D005434:Flow Cytometry; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D013058:Mass Spectrometry; D009103:Multiple Sclerosis / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D054464:Peroxiredoxins / Q000378:metabolism*; D040081:Protein Array Analysis; D051381:Rats; D011917:Rats, Inbred Lew; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000633:toxicity*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017382:Reactive Oxygen Species; D054464:Peroxiredoxins