Chronic exposure to low doses of ionizing radiation impacts the processing of glycoprotein N-linked glycans in Medaka (Oryzias latipes)

Ionizing radiation is found naturally in the environment. Low doses of IR may have beneficial applications, yet there is also potential for detrimental long-term health effects. Impacts following exposure to low levels of IR have been refractory to identification and quantification. Glycoprotein glycosylation is vital to cell–cell communication and organismal function, and sensitive to changes in an organism's macro- and cellular environment. We investigated whether accumulated low doses of IR (LoDIR) affect the N-linked glycoprotein glycans using Medaka fish (Oryzias latipes). State-of-the-art methods in radiation exposure and glycan analysis were applied to study N-glycan changes after 190 day exposure at three different rates of gamma irradiation (2.25, 21.01, and 204.3 mGy/day) in wild-type adult Medaka. Tissue N-glycans were analyzed following enzymatic release from extracted proteins. N-linked glycan profiles are dominated by complex type N-glycans modified with terminal sialic acid and core fucose. Fucosylation and sialylation of N-linked glycoprotein glycans are affected by LoDIR and a subset of N-glycans are involved in the organismal radio–response. This is the first indication that the glycome can be interrogated for biomarkers that report the impact of chronic exposure to environmental stressors, such as low-level IR.电离辐射（Ionizing radiation，IR）广泛存在于自然环境中。低剂量的IR可具备有益的应用场景，但同时也可能带来潜在的长期有害健康效应。低剂量IR暴露后产生的影响，始终难以被准确识别与量化。糖蛋白糖基化（glycoprotein glycosylation）对于细胞间通讯与机体功能至关重要，同时对生物体宏观及细胞层面的环境变化极为敏感。本研究以青鳉鱼（Oryzias latipes）为模型，探究低剂量累积电离辐射（LoDIR）是否会对N-连接糖蛋白聚糖（N-linked glycoprotein glycans）产生影响。本研究采用辐射暴露与聚糖分析领域的顶尖技术，对成年野生型青鳉鱼进行为期190天的γ射线辐照（gamma irradiation），设置三种不同辐照剂量率（2.25、21.01与204.3 mGy/天），以此探究N-聚糖的变化情况。研究人员通过酶解法从提取的蛋白质中释放组织N-聚糖，并对其进行分析。N-连接聚糖谱主要由末端修饰有唾液酸（sialic acid）与核心岩藻糖（core fucose）的复合型N-聚糖（complex type N-glycans）构成。低剂量累积电离辐射会影响N-连接糖蛋白聚糖的岩藻糖基化（fucosylation）与唾液酸化（sialylation）过程，且部分N-聚糖参与了机体的辐射应答反应。本研究首次证实，可通过糖组（glycome）筛选生物标志物（biomarker），以反映慢性暴露于低剂量电离辐射这类环境应激源（environmental stressors）所产生的影响。