Significant reduction of the GLUT3 level, but not GLUT1 level, was observed in the brain tissues of several scrapie experimental animals and scrapie-infected cell lines.
Glucose transporters 1 (GLUT1) and 3 (GLUT3) belong to the solute carrier family 2 (SLC2, facilitated glucose transporter) and are the two most important glucose transporters (GLUTs) in brain tissue, and between them, GLUT3 is the primary one for neurons, which is responsible for glucose uptake. To obtain insights into the possible alterations of GLUT1 and GLUT3 in transmissible spongiform encephalopathies (TSEs), the protein levels of GLUT1 and GLUT3 in the brain tissues of agents 263K- and 139A-infected hamsters, as well as agents 139A- and ME7-infected mice, were evaluated. Western blots, immunofluorescent assay (IFA), and immunohistochemical (IHC) assays revealed that at the terminal stages of the infection, GLUT3 level in the brain tissues of scrapie-infected rodents was significantly downregulated, while GLUT1 level remained almost unchanged. The decline of GLUT3 level was closely related with prolonged incubation time. In line with these results in vivo, the GLUT3 level in a prion persistently infected cell line SMB-S15 was also lower than that of its normal cell line SMB-PS. Moreover, the level of hypoxia-inducible factor-1 alpha (HIF-1α), which positively regulated the expressions of GLUTs, was also markedly downregulated in the brains of several scrapie-infected animals. In vitro glucose uptake assays illustrated a markedly decreased 2-[N-(7-nitrobenze-2-oxa-1,3-diazol-4-yl)amino]-2-deoxyglucose uptake activity in SMB-S15 cells. Our data indicate that the reduction of GLUT3 is a common phenomenon in prion diseases, which occurs much earlier than the appearance of clinical symptoms. Defect in glucose uptake and metabolism of neurons, like in other neurodegenerative diseases, for example, Alzheimer's disease (AD), may be one of the essential processes in the pathogenesis of prion diseases.
Department of Neurology, Xijing Hospital, the Fourth Military Medical University, No. 15, Changle West Road, Xi'an, 710032, People's Republic of China.
Yu-E
YE
Yan
Jin
J
Zhang
Ke
K
Wang
Yin
Y
Xu
Ke
K
Ren
Bao-Yun
BY
Zhang
Ming
M
Shi
Cao
C
Chen
Qi
Q
Shi
Chan
C
Tian
Gang
G
Zhao
Xiao-Ping
XP
Dong
D000818:Animals; D001921:Brain / Q000378:metabolism* / Q000473:pathology; D002460:Cell Line; D006224:Cricetinae; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000502:physiology*; D051272:Glucose Transporter Type 1 / Q000096:biosynthesis*; D051274:Glucose Transporter Type 3 / Q000096:biosynthesis*; D008647:Mesocricetus; D051379:Mice; D008810:Mice, Inbred C57BL; D012608:Scrapie / Q000378:metabolism* / Q000473:pathology
D051272:Glucose Transporter Type 1; D051274:Glucose Transporter Type 3; C495678:Slc2a1 protein, mouse; C495689:Slc2a3 protein, mouse