Allicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2
Allicin alleviates lead-induced hematopoietic stem cell aging by up-regulating PKM2
复制标题
大蒜素通过上调 PKM2 缓解铅诱导的造血干细胞衰老
DOI：
10.1042/bsr20190243
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发表时间：
2019-07-05
影响因子：
4
通讯作者：
Chen, Yan
中科院分区：
文献类型：
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作者：
Cai, Shi-zhong;Zhao, Li-na;Chen, Yan
造血干细胞衰老与造血功能障碍和疾病有关。我们以前的研究表明，铅暴露诱导造血干细胞功能下降。大蒜素，一种从大蒜中提取的化学物质，据报道具有抗氧化和抗炎作用。然而，大蒜素对铅毒性的生物学活性，特别是在造血系统中的作用尚不清楚。在这里，我们发现铅暴露引起HSC的衰老表型，包括细胞静止紊乱，自我更新功能和集落形成能力丧失，以及骨髓偏向分化，所有这些都导致小鼠严重的造血功能障碍。大蒜素灌胃可显著改善体内铅诱导的肝星状细胞衰老表型。铅暴露诱导的过氧化条件下，导致DNA损伤，减少糖酵解酶丙酮酸激酶M2亚型（PKM2），这是一个表型，这是显着改善大蒜素治疗的HSC。提示大蒜素可通过上调PKM2的表达来减轻铅诱导的HSC衰老，因此大蒜素可能是一种预防铅中毒的天然药物。
Hematopoietic stem cells (HSCs) aging is associated with hematopoietic dysfunction and diseases. Our previous study showed that lead exposure induced a functional decline in HSCs. Allicin, a chemical extracted from the garlic (Allium sativum L.), has been reported to have antioxidative and anti-inflammatory effects. However, the biological activities of allicin on lead-induced toxicity, especially in the hematopoietic system, remain unclear. Here, we found that lead exposure elicited aging phenotypes in HSCs, including perturbed cell quiescence, disabled self-renewal function and colony-forming ability, and myeloid-biased differentiation, all of which contributed to significant hematopoietic disorders in mice. Intragastric administration of allicin substantially ameliorated lead-induced HSCs aging phenotypes in vivo. Lead exposure induced a peroxide condition in HSCs leading to DNA damage, which reduced expression of the glycolytic enzyme pyruvate kinase M2 isoform (PKM2), a phenotype which was significantly ameliorated by allicin treatment. These findings suggested that allicin alleviated lead-induced HSCs aging by up-regulating PKM2 expression; thus, it could be a natural herb for preventing lead toxicity.