High-dose irradiation poses extreme risk of mortality from acute damage to the hematopoietic compartment and gastrointestinal tract. While bone marrow transplantation can reestablish the hematopoietic compartment, a more imminent risk of death is posed by gastrointestinal acute radiation syndrome (GI-ARS), for which there are no FDA-approved medical countermeasures. Although the mechanisms dictating the severity of GI-ARS remain incompletely understood, sialylation by ST6GAL1 has been shown to protect against radiation-induced apoptosis in vitro. Here, we used a C57BL/6 St6gal1-KO mouse model to investigate the contribution of ST6GAL1 to susceptibility to total body irradiation in vivo. Twelve gray total body ionizing γ-irradiation (TBI) followed by bone marrow transplant is not lethal to wild-type mice, but St6gal1-KO counterparts succumbed within 7 d. Both St6gal1-KO and wild-type animals exhibited damage to the GI epithelium, diarrhea and weight loss, but these symptoms became progressively more severe in the St6gal1-KO animals while wild-type counterparts showed signs of recovery by 120 h after TBI. Increased apoptosis in the GI tracts of St6gal1-KO mice and the absence of regenerative crypts were also observed. Together, these observations highlight an important role for ST6GAL1 in protection and recovery from GI-ARS in vivo.

中文翻译：

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唾液酸转移酶 ST6GAL1 可防止辐射引起的胃肠道损伤。

高剂量照射会因造血区室和胃肠道的急性损伤而造成极大的死亡风险。虽然骨髓移植可以重建造血区室，但胃肠道急性辐射综合征 (GI-ARS) 会带来更迫在眉睫的死亡风险，对此没有 FDA 批准的医疗对策。尽管决定 GI-ARS 严重程度的机制仍未完全了解，但 ST6GAL1 的唾液酸化已被证明可以在体外防止辐射诱导的细胞凋亡。在这里，我们使用 C57BL/6  St6gal1 -KO 小鼠模型来研究 ST6GAL1 对体内全身照射敏感性的贡献。12 次灰色全身电离 γ 辐射 (TBI) 后进行骨髓移植对野生型小鼠不致命，但St6gal1 -KO 对应物在 7 d 内死亡。无论ST6GAL1 -KO和野生型动物表现出对胃肠道上皮细胞，腹泻和消瘦的损伤，但这些症状在逐渐变得更严重ST6GAL1 -KO动物，而野生型对应TBI后出现复苏迹象的120小时。还观察到St6gal1 -KO 小鼠胃肠道细胞凋亡增加，并且没有再生隐窝。总之，这些观察结果突出了 ST6GAL1 在体内 GI-ARS 保护和恢复中的重要作用。