Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China.
Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, Chongqing Engineering Research Center for Nanomedicine, College of Preventive Medicine, Third Military Medical University, Chongqing 400038, China; Department of Hematology, Daping Hospital, Third Military Medical University, Chongqing 400036, China.
Exp Cell Res. 2018 Sep 15;370(2):409-416. doi: 10.1016/j.yexcr.2018.07.003. Epub 2018 Jul 4.
Ionizing radiation (IR) triggers the generation of reactive oxygen species (ROS), which shows potential roles in damaging the DNA and proteins at the nucleus, and eventually results in apoptosis and even cell death. Antioxidant agents can inhibit the generation of ROS after IR exposure. Tannic acid (TA), has an antioxidant activity involving in preventing cardiovascular and cerebrovascular diseases. However, little is known about the effects of TA on irradiation-induced apoptosis in megakaryocytes. Here, we evaluated the anti-radiation activity of TA in megakaryocytes. Our results showed that TA protected megakaryocytes from apoptosis induced by IR, attenuated IR-induced increases in the production of ROS, and inhibited the changes of mitochondrial membrane potential (MMP). Moreover, TA down-regulated NAPDH oxidase 1 (Nox1) expression, and decreased the phosphorylated levels of JNK and p38. Furthermore, JNK inhibitor could reduce apoptosis induced by X-irradiation in M07e cells. In vivo experiments confirmed that TA could promote the platelet recovery, reduce the percentage of apoptosis CD41 megakaryocytes in bone marrow and raise survival during 30 days in mice by total body irradiation. In conclusion, TA can protecte the megakaryocytes from apoptosis caused by IR through inhibiting Nox1 expression to reduce ROS generation and repressing JNK/p38 MAPK pathway activation.
电离辐射（IR）会引发活性氧（ROS）的产生，ROS 在破坏细胞核内的 DNA 和蛋白质方面具有潜在作用，最终导致细胞凋亡甚至死亡。抗氧化剂可以抑制 IR 暴露后 ROS 的产生。单宁酸（TA）具有抗氧化活性，涉及预防心血管和脑血管疾病。然而，关于 TA 对巨核细胞照射诱导凋亡的影响知之甚少。在这里，我们评估了 TA 在巨核细胞中的抗辐射活性。我们的结果表明，TA 可保护巨核细胞免受 IR 诱导的凋亡，减弱 IR 诱导的 ROS 产生增加，并抑制线粒体膜电位（MMP）的变化。此外，TA 下调 NADPH 氧化酶 1（Nox1）的表达，并降低 JNK 和 p38 的磷酸化水平。此外，JNK 抑制剂可减少 X 射线照射在 M07e 细胞中诱导的凋亡。体内实验证实，TA 可通过抑制 Nox1 表达来减少 ROS 的产生，并抑制 JNK/p38 MAPK 通路的激活，从而促进全身照射小鼠血小板的恢复，减少骨髓中凋亡 CD41 巨核细胞的百分比，并提高 30 天内的存活率。总之，TA 可以通过抑制 Nox1 表达来减少 ROS 的产生，并抑制 JNK/p38 MAPK 通路的激活，从而保护巨核细胞免受 IR 引起的凋亡。
