ABSTRACT
Objective:To elucidate the change of whole genome expression profile for the effect of melatonin on radiation-induced intestinal injury in mice.Methods:C57BL/6J male mice were administrated with melatonin at 10 mg/kg body weight by intraperitoneal injection once a day for five consecutive days before abdominal irradiation with 14 Gy of γ-rays. Small intestines were harvested 3 d after radiation. GO annotation and KEGG pathway of the differential genes involved in small intestine were explored by DNA microarray analysis.Results:Compared with the control group, 584 differential genes were up-regulated and 538 differential genes were down-regulated for administration group pre-irradiation. The overlapping differential genes were selected from the irradiated mice and the administrated mice pre-irradiation. There were 324 up-regulated genes and 246 down-regulated genes unique to the administrated mice pre-irradiation. GO annotation analysis of the differential genes indicated that the top 15 significantly enriched biological processes for the administrated mice pre-irradiation mainly included autophagosome assembly (GO: 0000045), autophagosome organization (GO: 1905037) and regulation of acute inflammatory response (GO: 0002673). The genes ATG12, ATG16L2 and AMBRA1 were involved in autophagosome assembly and autophagosome organization. The genes C3, CPN1, CD55, CFP, CNR1, C1QA, C2 and CREB3L3 were involved in the regulation of acute inflammation response. KEGG pathway analysis of the differential genes involved indicated that the top 15 significantly enriched pathways for the administrated mice pre-irradiation mainly included O-glycan biosynthesis (hsa00512), glycosphingolipid biosynthesis (hsa00603), ECM-receptor interaction (hsa04512) and biosynthesis of unsaturated fatty acids (hsa01040). qRT-PCR verification showed that the expressions of ATG12 and ATG16L2 genes involved in autophagy for the administrated mice pre-irradiation increased significantly compared with the irradiated mice ( t=2.40, 4.35, P<0.05). Conclusions:The differential genes related with the biological process of autophagy, acute inflammatory response and the pathway of unsaturated fatty acid biosynthesis might be involved in the effect of melatonin on radiation-induced intestinal injury.
ABSTRACT
Uno de los retos más importantes de este siglo en la neurología genómica es construir mapas de expresión espacial de genes a lo largo de las distintas estructuras cerebrales con el fin de correlacionarlos con ciertas neuropatologías. Se analizaron los perfiles de transcripción de ocho genes HAS21 localizados en la región crítica del síndrome de Down en diferentes estructuras del cerebro humano normal. Se tomaron como referencia los valores de expresión de ocho genes HAS21/DSCR provenientes de experimentos de micromatrices de ADN de cerebros humanos normales y cuyos valores están disponibles en la base de datos del proyecto cerebro humano del Atlas del Cerebro del Allen Institute for Brain Sciences en Seattle, Washington (http://www.brainmap.org). Se determinó una expresión diferencial de estos genes HAS21/DSCR a lo largo de las estructuras localizadas en el lóbulo frontal, el lóbulo límbico y en los núcleos centrales. En el putamen, el núcleo caudado, el giro parahipocampal y en las áreas centrales se registraron los mayores niveles de transcripción global; estas áreas del cerebro parecen estar asociadas con diversos procesos de aprendizaje y de memoria. Se correlacionó la transcripción diferencial de genes DSCR con la localización cerebral y su potencial papel funcional.
One of the most important challenges of the 21st Century Neurology is to build gene expression profiles along the different structures of human brain trying to correlate them with some neuropathologies. The expression profiles of eight HAS21 genes located on the Down syndrome critical region in different structures of the normal human brain was analyzed. From DNA microarray experiments of normal human brains which are available in the free access human brain database of the Brain Atlas project of the Allen Institute for Brain Sciences in Seattle, Washington (http://www.brainmap.org) expression levels data of eight HSA21/DSCR genes along different structures of normal human brain were statistically analyzed. A differential expression of these genes HSA21/DSCR in some anatomic structures located in the frontal lobe, limbic lobe and cerebral central nuclei was registered. Putamen, caudate nucleus, parahipocampal gyro and central areas, showed high levels of transcription for those HSA21/DSCR genes included in the study; these areas of the brain appear to be associated with some processes of learning and memory. This study allowed us to correlate the differential transcription of DSCR genes, their structural localization and functional role in brain function.
Um dos maiores desafio deste século na neurologia genômica é construir mapas de expressão espacial de genes ao longo das diferentes estruturas cerebrais com o fim de correlacionálos com certas neuropatologias. Foram analisados os perfis de transcrição de oito genes HAS21 localizados na região crítica da síndrome de Down em diferentes estruturas do cérebro humano normal. Foram usados como referência os valores de expressão de oito genes HAS21/DSCR provenientes de experimentos de micromatrizes de ADN de cérebros humanos normais e cujos valores estão disponíveis no bando de dados do projeto cérebro humano do Atlas do Cérebro do Allen Institute for Brain Sciences em Seattle, Washington (http://www.brainmap.org). Determinouse uma expressão diferencial destes genes HAS21/DSCR ao longo das estruturas localizadas no lóbulo frontal, o lóbulo límbico e nos núcleos centrais. No putâmen, o núcleo caudado, o giro parahipocampal e nas áreas centrais foram registrados os maiores níveis de transcrição global; estas áreas do cérebro parecem estar associadas com diversos processos de aprendizagem e de memória. Correlacionouse a transcrição diferencial de genes DSCR com a localização cerebral e seu potencial papel funcional.