Vascular Homeostasis Regulators, Edn1 and Agpt2, are Upregulated as a Protective Effect of Heat-treated Zinc Yeast in Irradiated Murine Bone Marrow

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  • UENO Megumi
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
  • IMADOME Kaori
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
  • IWAKAWA Mayumi
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
  • ANZAI Kazunori
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences
  • IKOTA Nobuo
    Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences School of Pharmacy, Shujitsu University
  • IMAI Takashi
    Research Center for Charged Particle Therapy, National Institute of Radiological Sciences

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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.

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