Upregulation of Ras homolog enriched in the brain (Rheb) in lipopolysaccharide-induced neuroinflammation

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• 作者：Maohong Cao¹ ; Xiang Tan¹ ; Wei Jin ; Heyi Zheng ; Wei Xu ; Ying Rui ; Lei Li ; Jianhua Cao ; Xiaohong Wu ; Gang Cui ; Kaifu Ke ; ^{kaifuke-nt@hotmail.com} ; Yilu Gao ; ^{YiluGao123@hotmail.com}
• 关键词：Lipopolysaccharide ; Rheb ; Neuroinflammation ; Astrocyte ; Neuron ; Rat
• 刊名：Neurochemistry International
• 出版年：2013
• 出版时间：March, 2013
• 年：2013
• 卷：62
• 期：4
• 页码：406-417
• 全文大小：3445 K

文摘

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.