ニュートリゲノミクスからみた高血糖による遺伝子発現変化とアスタキサンチン

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Diabetic nephropathy is characterized by the proliferation of glomerular mesangium cells and the accumulation of extra-cellular matrix. We recently demonstrated that astaxanthin reduced glomerular oxidative stress as well as inhibited the increase of urinary albumin in diabetic db/db mice. The aim of the present study is to determine the gene expression patterns in glomerular cells of astaxanthin-treated mice by using a microarray technique. The diet for the astaxanthin supplementation group was prepared by mixing control powder with astaxanthin at 0.02%. Glomerular cells were obtained from the kidneys of mice by laser capture microdissection according to the previously reported method. Preparation of cRNA and target hybridization was performed according to the Affymetrix GeneChip Eukarryotic Small Sample Target Labeling Assay Protocol. The gene expression profile was determined by the mouse expression set 430A GeneChip. The DNA chips were scanned using a specially designed con focal scanner (GeneChip Scanenr 3000, Affymetrix). Array data analysis was done using Affymetrix GeneChip Operating Software (GCOS) version 1.0 and the Ingenuity Pathway Analysis software (Ingenuity Systems, Mountain View, CA). By comparison between diabetic db/db and non-diabetic db/m mice, 779 probes (3.1%) were significantly affected, up-regulated 550 probes and down-regulated 229 probes, at least 1.5-fold in the diabetic mice. Ingenuity signal analysis for up-regulated 550 probes determined the mitochondrial oxidative phosphorylation pathway as a most significantly affected caronical pathway. These genes are associated with complex I, III, and IV located in the inner mitochondrial membrane, and the expression level of them was decreased in mice treated with astaxanthin. In addition, the expression of many genes associated with oxidative stress, cytokine, collagen synthesis, and TGF-b signaling was enhanced in diabetic mice, and this enhancement was significantly decreased in the astaxanthin-treated mice. In conclusion, this genome-wide nutrigenomics approach provided insight into genes and genetic putative pathways that affected by the high-glucose stimulation as well as those involved in the anti-diabetic mechanism of astaxanthin.
日本ビタミン学会の論文
2006-07-25

ニュートリゲノミクスからみた高血糖による遺伝子発現変化とアスタキサンチン

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