Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2.
Accelerated apoptotic death and in vivo turnover of erythrocytes in mice lacking functional mitogen- and stress-activated kinase MSK1/2.
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DOI：
10.1038/srep17316
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发表时间：
2015-11-27
影响因子：
4.6
通讯作者：
Qadri SM
中科院分区：
文献类型：
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作者：
Lang E;Bissinger R;Fajol A;Salker MS;Singh Y;Zelenak C;Ghashghaeinia M;Gu S;Jilani K;Lupescu A;Reyskens KM;Ackermann TF;Föller M;Schleicher E;Sheffield WP;Arthur JS;Lang F;Qadri SM
丝裂原和应激激活激酶MSK 1/2在细胞凋亡中起决定性作用。与有核细胞的凋亡类似，称为红细胞凋亡的自杀性红细胞死亡的特征在于细胞收缩和细胞膜混乱，导致磷脂酰丝氨酸（PS）外化。在这里，我们探讨了是否MSK 1/2参与调节红细胞凋亡。为此，从缺乏功能性MSK 1/2的小鼠（msk-/-）和相应的野生型小鼠（msk+/+）中分离红细胞。血细胞计数、红细胞压积、血红蛋白浓度和平均红细胞体积在msk−/−和msk+/+小鼠中相似，但网织红细胞计数在msk−/−小鼠中显著增加。在未处理的msk−/−和msk+/+红细胞中，细胞膜PS暴露相似，但通过离体病理生理细胞应激源（如高渗休克或能量消耗）增强，msk−/−红细胞中的PS暴露水平显著高于msk+/+红细胞。在msk−/−红细胞中，高渗休克和能量消耗后的细胞收缩以及细胞外渗透压降低后的溶血更为明显。在msk−/−小鼠中，自体输注CFSE标记的红细胞从循环血液中的体内清除速度更快。来自msk−/−小鼠的脾脏比来自msk+/+小鼠的脾脏含有显著更多数量的PS暴露红细胞。目前的观察结果表明，在MSK 1/2缺陷小鼠中，红细胞的加速凋亡和随后的清除导致红细胞周转增强。
The mitogen- and stress-activated kinase MSK1/2 plays a decisive role in apoptosis. In analogy to apoptosis of nucleated cells, suicidal erythrocyte death called eryptosis is characterized by cell shrinkage and cell membrane scrambling leading to phosphatidylserine (PS) externalization. Here, we explored whether MSK1/2 participates in the regulation of eryptosis. To this end, erythrocytes were isolated from mice lacking functional MSK1/2 (msk−/−) and corresponding wild-type mice (msk+/+). Blood count, hematocrit, hemoglobin concentration and mean erythrocyte volume were similar in both msk−/− and msk+/+ mice, but reticulocyte count was significantly increased in msk−/− mice. Cell membrane PS exposure was similar in untreated msk−/− and msk+/+ erythrocytes, but was enhanced by pathophysiological cell stressors ex vivo such as hyperosmotic shock or energy depletion to significantly higher levels in msk−/− erythrocytes than in msk+/+ erythrocytes. Cell shrinkage following hyperosmotic shock and energy depletion, as well as hemolysis following decrease of extracellular osmolarity was more pronounced in msk−/− erythrocytes. The in vivo clearance of autologously-infused CFSE-labeled erythrocytes from circulating blood was faster in msk−/− mice. The spleens from msk−/− mice contained a significantly greater number of PS-exposing erythrocytes than spleens from msk+/+ mice. The present observations point to accelerated eryptosis and subsequent clearance of erythrocytes leading to enhanced erythrocyte turnover in MSK1/2-deficient mice.