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A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion.

Mitsios N, Saka M, Krupinski J, Pennucci R, Sanfeliu C, Wang Q, Rubio F, Gaffney J, Kumar P, Kumar S, Sullivan M, Slevin M - BMC Neurosci (2007)

Bottom Line: Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases.Interestingly, the mean fold changes were much higher in the human.Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology, Chemistry and Health Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, UK. n.mitsios@mmu.ac.uk

ABSTRACT

Background: Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain.

Results: Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11.

Conclusion: Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.

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Related in: MedlinePlus

Statistical analysis of microarray data. Total number of genes and number of overlapping genes (between the two array sets) deregulated following stroke in human and rat (A). Scatter plots representing the data dispersion over two logarithmic scales for all time-points in human (B) and rat (C).
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Figure 1: Statistical analysis of microarray data. Total number of genes and number of overlapping genes (between the two array sets) deregulated following stroke in human and rat (A). Scatter plots representing the data dispersion over two logarithmic scales for all time-points in human (B) and rat (C).

Mentions: The expression of ischemia-related genes was determined by comparing the infarct-induced expression (combined samples from infarcted and peri-infarcted areas) to that in the contralateral hemisphere: 77, 92 and 15 genes were de-regulated in stroke-affected regions in the 3 patient survival groups respectively, while 9, 51, 48, 166, 253, 117 and 261 genes were altered at the 7 different time-points in the animal model compared to the controls (Figure 1). The combined number of differentially expressed transcripts in stroke patients represented 6.5%, 7.8% and 1.3% respectively in each survival group of the total number of the genes on the microarray. These findings compare with 0.8%, 4.3%, 4%, 14.1%, 21.5%, 10% and 22.2% of genes respectively at each time-point in rats.


A microarray study of gene and protein regulation in human and rat brain following middle cerebral artery occlusion.

Mitsios N, Saka M, Krupinski J, Pennucci R, Sanfeliu C, Wang Q, Rubio F, Gaffney J, Kumar P, Kumar S, Sullivan M, Slevin M - BMC Neurosci (2007)

Statistical analysis of microarray data. Total number of genes and number of overlapping genes (between the two array sets) deregulated following stroke in human and rat (A). Scatter plots representing the data dispersion over two logarithmic scales for all time-points in human (B) and rat (C).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2194693&req=5

Figure 1: Statistical analysis of microarray data. Total number of genes and number of overlapping genes (between the two array sets) deregulated following stroke in human and rat (A). Scatter plots representing the data dispersion over two logarithmic scales for all time-points in human (B) and rat (C).
Mentions: The expression of ischemia-related genes was determined by comparing the infarct-induced expression (combined samples from infarcted and peri-infarcted areas) to that in the contralateral hemisphere: 77, 92 and 15 genes were de-regulated in stroke-affected regions in the 3 patient survival groups respectively, while 9, 51, 48, 166, 253, 117 and 261 genes were altered at the 7 different time-points in the animal model compared to the controls (Figure 1). The combined number of differentially expressed transcripts in stroke patients represented 6.5%, 7.8% and 1.3% respectively in each survival group of the total number of the genes on the microarray. These findings compare with 0.8%, 4.3%, 4%, 14.1%, 21.5%, 10% and 22.2% of genes respectively at each time-point in rats.

Bottom Line: Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases.Interestingly, the mean fold changes were much higher in the human.Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.

View Article: PubMed Central - HTML - PubMed

Affiliation: School of Biology, Chemistry and Health Science, John Dalton Building, Manchester Metropolitan University, Chester Street, Manchester, UK. n.mitsios@mmu.ac.uk

ABSTRACT

Background: Altered gene expression is an important feature of ischemic cerebral injury and affects proteins of many functional classes. We have used microarrays to investigate the changes in gene expression at various times after middle cerebral artery occlusion in human and rat brain.

Results: Our results demonstrated a significant difference in the number of genes affected and the time-course of expression between the two cases. The total number of deregulated genes in the rat was 335 versus 126 in the human, while, of 393 overlapping genes between the two array sets, 184 were changed only in the rat and 36 in the human with a total of 41 genes deregulated in both cases. Interestingly, the mean fold changes were much higher in the human. The expression of novel genes, including p21-activated kinase 1 (PAK1), matrix metalloproteinase 11 (MMP11) and integrase interactor 1, was further analyzed by RT-PCR, Western blotting and immunohistochemistry. Strong neuronal staining was seen for PAK1 and MMP11.

Conclusion: Our findings confirmed previous studies reporting that gene expression screening can detect known and unknown transcriptional features of stroke and highlight the importance of research using human brain tissue in the search for novel therapeutic agents.

Show MeSH
Related in: MedlinePlus