Melatonin protects against apoptosis of megakaryocytic cells via its receptors and the AKT/mitochondrial/caspase pathway
Melatonin protects against apoptosis of megakaryocytic cells via its receptors and the AKT/mitochondrial/caspase pathway
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褪黑激素通过其受体和 AKT/线粒体/半胱天冬酶途径防止巨核细胞凋亡
DOI：
10.18632/aging.103483
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发表时间：
2020-07
期刊：
影响因子：
5.2
通讯作者：
Ye Jieyu
中科院分区：
文献类型：
--
作者：
Yang Mo;Li Liang;Chen Shichao;Li Suyi;Wang Bo;Zhang Changhua;Chen Youpeng;Yang Liuming;Xin Hongwu;Chen Chun;Xu Xiaojun;Zhang Qing;He Yulong;Ye Jieyu
临床研究表明，褪黑素可降低接受放疗或化疗的癌症患者的血小板减少的频率。在这里，我们研究了褪黑素促进血小板形成和存活的机制。结果表明，褪黑素对无血清诱导的CHRF巨核细胞(MKs)的凋亡具有保护作用。褪黑素以剂量依赖的方式促进MK集落形成单位(CFU)的形成。利用阿霉素处理的CHRF细胞，我们发现褪黑素可以挽救阿霉素诱导的G2/M期细胞周期停滞和细胞凋亡。褪黑素可增加p-AKT的表达，褪黑素受体阻滞剂可阻断这一作用。此外，我们还证明了褪黑素能促进辐射小鼠模型中的血小板恢复。在接受褪黑激素治疗的小鼠中，巨核细胞的生成在很大程度上得以保存。我们在体内的骨髓组织学和CFU-MK形成实验中得到了相同的结果。褪黑素可能通过激活其受体和AKT信号，直接刺激巨核细胞的生成，抑制巨核细胞的凋亡，从而发挥这些保护作用。
Clinical studies have shown that melatonin lowers the frequency of thrombocytopenia in patients with cancer undergoing radiotherapy or chemotherapy. Here, we investigated the mechanisms by which melatonin promotes platelet formation and survival. Our results show that melatonin exerted protective effects on serum-free induced apoptosis of CHRF megakaryocytes (MKs). Melatonin promoted the formation of MK colony forming units (CFUs) in a dose-dependent manner. Using doxorubicin-treated CHRF cells, we found that melatonin rescued G2/M cell cycle arrest and cell apoptosis induced by doxorubicin. The expression of p-AKT was increased by melatonin treatment, an effect that was abolished by melatonin receptor blocker. In addition, we demonstrated that melatonin enhanced the recovery of platelets in an irradiated mouse model. Megakaryopoiesis was largely preserved in melatonin-treated mice. We obtained the same results in vivo from bone marrow histology and CFU-MK formation assays. Melatonin may exert these protective effects by directly stimulating megakaryopoiesis and inhibiting megakaryocyte apoptosis through activation of its receptors and AKT signaling.
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影响因子：
9
作者：
通讯作者：
--
影响因子：
64.8
作者：
M. Spitschan
通讯作者：
M. Spitschan
影响因子：
64.5
作者：
Manning BD;Toker A
通讯作者：
Toker A
影响因子：
37.8
作者：
Li, K;Sung, RYT;Ng, PC
通讯作者：
Ng, PC
影响因子：
64.8
作者：
L. Johansson;B. Stauch;J. McCorvy;G. Han;N. Patel;Xi Ping Huang;A. Batyuk;C. Gati;Samuel T. Slocum;Chufeng Li;J. Grandner;S. Hao;Reid H. J. Olsen;A. Tribo;S. Zaare;Lan Zhu;N. Zatsepin;U. Weierstall;S. Yous;R. Stevens;Wei Liu;B. Roth;V. Katritch;V. Cherezov
通讯作者：
L. Johansson;B. Stauch;J. McCorvy;G. Han;N. Patel;Xi Ping Huang;A. Batyuk;C. Gati;Samuel T. Slocum;Chufeng Li;J. Grandner;S. Hao;Reid H. J. Olsen;A. Tribo;S. Zaare;Lan Zhu;N. Zatsepin;U. Weierstall;S. Yous;R. Stevens;Wei Liu;B. Roth;V. Katritch;V. Cherezov