Small interfering RNA-mediated xCT silencing in gliomas inhibits neurodegeneration and alleviates brain edema.
Neurodegeneration and brain edema are hallmarks of human malignant brain tumors. Here we show that genetic or pharmacological inhibition of the glutamate transporter xCT (X(c-) system, encoded by SLC7a11) in vivo leads to abrogated neurodegeneration, attenuated perifocal edema and prolonged survival. These results show a crucial role for xCT in glioma-induced neurodegeneration and brain edema, corroborating the concept that edema formation may be in part a consequence of peritumoral cell death.
Savaskan
Nicolai E
NE
Brain Research Institute, Swiss Federal Institute of Technology & University Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland.
Heckel
Alexandra
A
Hahnen
Eric
E
Engelhorn
Tobias
T
Doerfler
Arnd
A
Ganslandt
Oliver
O
Nimsky
Christopher
C
Buchfelder
Michael
M
Eyüpoglu
Ilker Y
IY
D027182:Amino Acid Transport System y+ / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism; D001929:Brain Edema / Q000473:pathology*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D020868:Gene Silencing; D005910:Glioma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D019636:Neurodegenerative Diseases / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000378:metabolism*
D027182:Amino Acid Transport System y+; D034741:RNA, Small Interfering; C118895:SLC7A11 protein, human