PMID- 23391520
OWN - NLM
STAT- MEDLINE
DCOM- 20130920
LR  - 20130319
IS  - 1872-9754 (Electronic)
IS  - 0197-0186 (Linking)
VI  - 62
IP  - 4
DP  - 2013 Mar
TI  - Upregulation of Ras homolog enriched in the brain (Rheb) in 
      lipopolysaccharide-induced neuroinflammation.
PG  - 406-17
LID - S0197-0186(13)00034-X [pii]
LID - 10.1016/j.neuint.2013.01.025 [doi]
AB  - Ras homolog enriched in the brain (Rheb) is a homolog of Ras GTPase that 
      regulates cell growth, proliferation, and cell cycle via mammalian target of 
      rapamycin (mTOR). Recently, it has been confirmed that Rheb activation not only 
      promotes cellular proliferation and differentiation but also enhances cellular 
      apoptosis in response to diverse toxic stimuli. However, the function of Rheb in 
      the central nervous system (CNS) is still with limited understanding. To 
      elaborate whether Rheb was involved in CNS injury, we performed a 
      neuroinflammatory model by lipopolysaccharide (LPS) lateral ventral injection in 
      adult rats. Upregulation of Rheb was observed in the brain cortex by performing 
      western blotting and immunohistochemistry. Double immunofluorescent staining 
      demonstrated that Rheb was mainly in active astrocytes and neurons. PCNA and 
      active caspase-3 were upregulated, and co-labeling with Rheb, which indicated 
      that Rheb might be relevant to astrocytic proliferation and neuronal apoptosis 
      following the inflammatory response by LPS-induced. Furthermore, we also found 
      that the expression profiles of cyclinD1 and CDK4 were parallel with that of Rheb 
      in a time-space dependent manner. Finally, knocking down Rheb by siRNA and 
      treatment with rapamycin or lovastatin showed that not only astrocytic 
      proliferation decreased but also neuronal protection. Based on our data, we 
      suggested that Rheb might play an important role in physiological and 
      pathological functions following neuroinflammation caused by LPS, which might 
      provide a potential target to the treatment of neuroinflammation.
CI  - Copyright (c) 2013 Elsevier Ltd. All rights reserved.
FAU - Cao, Maohong
AU  - Cao M
AD  - Department of Neurology, Affiliated Hospital of Nantong University, Nantong, 
      Jiangsu Province 226001, People's Republic of China.
FAU - Tan, Xiang
AU  - Tan X
FAU - Jin, Wei
AU  - Jin W
FAU - Zheng, Heyi
AU  - Zheng H
FAU - Xu, Wei
AU  - Xu W
FAU - Rui, Ying
AU  - Rui Y
FAU - Li, Lei
AU  - Li L
FAU - Cao, Jianhua
AU  - Cao J
FAU - Wu, Xiaohong
AU  - Wu X
FAU - Cui, Gang
AU  - Cui G
FAU - Ke, Kaifu
AU  - Ke K
FAU - Gao, Yilu
AU  - Gao Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130204
PL  - England
TA  - Neurochem Int
JT  - Neurochemistry international
JID - 8006959
RN  - 0 (Lipopolysaccharides)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/*metabolism/pathology
MH  - Lipopolysaccharides/*pharmacology
MH  - Male
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - *Up-Regulation
EDAT- 2013/02/09 06:00
MHDA- 2013/09/21 06:00
CRDT- 2013/02/09 06:00
PHST- 2012/08/01 00:00 [received]
PHST- 2012/12/16 00:00 [revised]
PHST- 2013/01/26 00:00 [accepted]
PHST- 2013/02/09 06:00 [entrez]
PHST- 2013/02/09 06:00 [pubmed]
PHST- 2013/09/21 06:00 [medline]
AID - S0197-0186(13)00034-X [pii]
AID - 10.1016/j.neuint.2013.01.025 [doi]
PST - ppublish
SO  - Neurochem Int. 2013 Mar;62(4):406-17. doi: 10.1016/j.neuint.2013.01.025. Epub 
      2013 Feb 4.