کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1990361 1540679 2012 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Investigation of the molecular response to folate metabolism inhibition
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی زیست شیمی
پیش نمایش صفحه اول مقاله
Investigation of the molecular response to folate metabolism inhibition
چکیده انگلیسی

We investigated the molecular response to folate metabolism inhibition by exposing human lymphoblast cell lines to the methionine adenosyltransferase inhibitor cycloleucine. We carried out microarray analysis on replicate control and exposed cells by examining 47,000 transcripts on the Affymetrix HG U133 plus 2.0 arrays. We identified 13 genes that we considered reliable responders to cycloleucine treatment: chemokine receptor 3 (CXCR3), prostaglandin-endoperoxide synthase 2, growth arrest-specific 7, reduced folate carrier, klotho beta, early growth response 1, diaphanous homolog 3, prostaglandin D2 synthase (PGDS), butyrophilin-like 9, low-density lipoprotein receptor-related protein 11, chromosome 21 orf15, G-protein-coupled receptor 98 (GPR98) and cystathionine-beta-synthase (CBS). We further demonstrated that four of these genes, CXCR3, PGDS, GPR98 and CBS, consistently responded to cycloleucine treatment in additional experiments over a range of concentrations. We carried out gene-specific DNA methylation analysis on five genes, including CBS, and found no evidence that DNA methylation changes were mediating the gene expression changes observed. Pathway analysis of the microarray data identified four pathways of relevance for response to cycloleucine; the immune response NF-AT signaling pathway was the most statistically significant. Comparison with other gene expression studies focusing on folate deficiency revealed that gene products related to immune cells or the immune response is a common theme. This indicates that apart from their role in the immune response, it is likely that these gene products may also have a role to play in the cellular response to folate status.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: The Journal of Nutritional Biochemistry - Volume 23, Issue 11, November 2012, Pages 1531–1536
نویسندگان
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