Vascular homeostasis regulators,Edn1 and Agpt2,are upregulated as a protective effect of heat-treated zinc yeast in irradiated murine bone marrow

Purpose: to elucidate the mechanism underlying the in vivo radioprotection activity by zn-containing,heat-treated saccharomyces cerevisiae yeast (zn-yeast). materials and methods: zn-yeast suspension was administered into c3h/he mice immediately after whole body irradiation (wbi) at 7.5 gy. bone marrow was extracted from the mice 6 hours after irradiation and analyzed on a microarray. expression changes in the candidate responsive genes differentially expressed in treated mice were re-examined by qrt-pcr. the bone marrow was also examined pathologically at 6 h,3,7,and 14 days postirradiation. results: thirty-six genes,including edn1 and agpt2,were identified as candidate responsive genes in irradiated mouse bone marrow treated with zn-yeast by showing a greater than three-fold change compared with control (no irradiation and no zn-yeast) mice. the expressions of cdkn1a,bax,and ccng,which are well known as radioresponsive genes,were upregulated in wbi mice and zn-yeast treated wbi mice. pathological examination showed the newly formed microvessels lined with endothelial cells,and small round hematopoietic cells around vessels in bone marrow matrix of mice administered with zn-yeast after wbi,while whole-body irradiated mice developed fatty bone marrow within 2 weeks after irradiation. conclusion: this study identified a possible mechanism for the postirradiation protection conferred by zn-yeast. the protective effect of zn-yeast against wbi is related to maintaining the bone marrow microenvironment,including targeting endothelial cells and cytokine release.