NF-泻B-regulated micro RNAs (miRNAs) in primary human brain cells
- 作者：Walter J. Lukiw wlukiw@lsuhsc.edu
- 关键词：15-LOX ; 15-lipoxygenase ; AD ; Alzheimer's disease ; CFH ; complement factor H ; HNG ; human neuronal-glial ; LPS ; lipopolysaccharide ; miRNA ; micro RNA ; PDTC ; pyrollidine dithiocarbamate ; SYN-2 ; (SYN-II ; synapsin-2) ; TNF伪 ; tumor necrosis factor alpha ; TSPAN-12
- 刊名：Experimental Neurology
- 出版年：2012
- 期刊代码：78_00144886
- 类别：neu
- 出版时间：June, 2012
- 卷：235
- 期：2
- 页码：484-490
- 文件大小：667 K
摘要
Micro RNAs (miRNAs), small and labile ~ 22 nucleotide-sized fragments of single stranded RNA, are important regulators of messenger (mRNA) complexity and in shaping the transcriptome of a cell. In this communication, we utilized amyloid beta 42 (A尾42) peptides and interleukin-1beta (IL-1尾) as a combinatorial, physiologically-relevant stress to induce miRNAs in human primary neural (HNG) cells (a co-culture of neurons and astroglia). Specific miRNA up-regulation was monitored using miRNA arrays, Northern micro-dot blots and RT-PCR. Selective NF-泻B translocation and DNA binding inhibitors, including the chelator and anti-oxidant pyrollidine dithiocarbamate (PDTC) and the polyphenolic resveratrol analog CAY10512 (trans-3,5,4鈥?trihydroxystilbene), indicated the NF-泻B sensitivity of several brain miRNAs, including miRNA-9, miRNA-125b and miRNA-146a. The inducible miRNA-125b and miRNA-146a, and their verified mRNA targets, including 15-lipoxygenase (15-LOX), synapsin-2 (SYN-2), complement factor H (CFH) and tetraspanin-12 (TSPAN12), suggests complex and highly interactive roles for NF-泻B, miRNA-125b and miRNA-146a. These data further indicate that just two NF-泻B-mediated miRNAs have tremendous potential to contribute to the regulation of neurotrophic support, synaptogenesis, neuroinflammation, innate immune signaling and amyloidogenesis in stressed primary neural cells of the human brain.