Phosphorylation of mitogen-activated protein kinase 8 (MAPK8) is associated with germ cell apoptosis and redistribution of the Bcl2-modifying factor (BMF).
Phosphorylation of mitogen-activated protein kinase 8 (MAPK8) is associated with germ cell apoptosis and redistribution of the Bcl2-modifying factor (BMF).
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DOI：
10.2164/jandrol.107.003558
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发表时间：
2008-05
影响因子：
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通讯作者：
Matthew D Show;Christine M. Hill;M. D. Anway;W. Wright;B. Zirkin
中科院分区：
文献类型：
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作者：
Matthew D Show;Christine M. Hill;M. D. Anway;W. Wright;B. Zirkin
成功的精子发生需要生殖细胞与支持细胞保持物理接触，直到精子形成。以前的研究已经表明，Bcl 2修饰因子（BMF）是在许多上皮细胞中发现的促凋亡蛋白，当其被有丝分裂原活化蛋白激酶8（p-MAPK 8）的活性形式磷酸化时，响应于细胞与其基底层的粘附的丧失而启动凋亡。基于此，我们推测p-MAPK 8和BMF可能在睾丸生殖细胞从支持细胞脱离后的凋亡中起重要作用。正常大鼠睾丸的免疫组化分析显示p-MAPK 8在精母细胞和细长精子细胞中表达，但在圆形精子细胞中不表达。这一定位与BMF相反，BMF在圆形精子细胞中表达，但在精母细胞或细长精子细胞中不表达。当新鲜分离的生殖细胞在不存在支持细胞的情况下培养时，通过Western印迹分析观察到存在广泛生殖细胞凋亡的条件，即p-MAPK 8相对于总体MAPK 8蛋白的增加。此外，免疫细胞化学分析显示，与BMF表达相关的圆形精子细胞和精母细胞中免疫反应性p-MAPK 8增加。从这些相关的数据，我们提出，MAPK 8的激活和BMF的重新分配可能是整体参与的机制，通过该机制，特定的生殖细胞进行程序性细胞死亡，以响应其脱离支持细胞。
Successful spermatogenesis requires that germ cells remain in physical contact with Sertoli cells until spermiation. Previous studies have shown that the Bcl2-modifying factor (BMF) is a proapoptotic protein found in many epithelial cells which, when phosphorylated by the active form of mitogen-activated protein kinase 8 (p-MAPK8), initiates apoptosis in response to loss of adhesion of the cells to their basal lamina. Based on this, we hypothesized that p-MAPK8 and BMF may play important roles in the apoptotic death of testicular germ cells in response to their detachment from Sertoli cells. Immunohistochemical analysis of the normal rat testis revealed p-MAPK8 expression in spermatocytes and elongated spermatids but not in round spermatids. This localization was opposite to that of BMF, which is expressed in round spermatids but not in spermatocytes or elongated spermatids. When freshly isolated germ cells were cultured in the absence of Sertoli cells, a condition in which there was widespread germ cell apoptosis, an increase in p-MAPK8 relative to overall MAPK8 protein, was seen by Western blot analysis. Additionally, immunocytochemical analysis showed an increase in immunoreactive p-MAPK8 in round spermatids and spermatocytes in association with BMF expression. From these correlative data, we propose that the activation of MAPK8 and redistribution of BMF may be integrally involved in the mechanism by which specific germ cells undergo programmed cell death in response to their detachment from Sertoli cells.