Bion-M1和航天飞机STS-135任务后唾液腺蛋白的表达

M. Mednieks, A. Khatri, A. Hand
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引用次数: 5

摘要

唾液腺分泌的蛋白储存在颗粒中并释放到唾液中。啮齿动物的唾液腺在形态和功能上与人类的唾液腺相似,因此是一个可靠的实验模型。为了确定微重力对分泌蛋白的影响是否会随着飞行时间的延长而增加,我们采用了形态学、免疫细胞化学和生化/分子方法研究了它们在小鼠腮腺中的表达。STS-135(13天)和Bion-M1(30天)飞行动物的腺泡细胞自噬和凋亡增加,导管细胞含有内吞蛋白的空泡。免疫金标法检测STS-135细胞ⅱ型蛋白激酶A (RII)调控亚基降低(p<0.01),富含脯氨酸的蛋白(PRPs, p<0.001)和腮腺分泌蛋白(PSP, p<0.05)升高。这些结果表明微重力对分泌的影响是功能依赖的。微阵列分析显示,许多基因的表达发生了显著变化,包括环-3 ',5 ',-腺苷单磷酸(cyclic AMP)信号通路的成分。与栖息地地面对照相比,来自两个飞行的小鼠表现出环amp特异性磷酸二酯酶、腺苷酸环化酶异构体和几种a激酶锚定蛋白的表达改变。Bion-M1飞行小鼠显示溶菌酶和淀粉酶基因表达增加,PRPs基因表达减少,RII基因表达与对照组相比没有变化。在太空旅行中,分泌蛋白的表达发生了改变,这代表了对微重力条件的可逆调整。最终的目标是开发一种使用唾液(一种容易获得的体液)的测试试剂盒,以评估太空旅行的生理影响。
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Salivary Gland Protein Expression after Bion-M1 and Space Shuttle STS-135 Missions
ABSTRACT Secretory proteins produced by salivary glands are stored in granules and released into saliva. Rodent salivary glands are a reliable experimental model because they are morphologically and functionally similar to those of humans. To determine if the effects of microgravity on secretory proteins are increased on extended flights, their expression in mouse parotid glands, morphological, immunocytochemical, and biochemical/molecular methods were employed. Acinar cells of STS-135 (13 day) and Bion-M1 (30 day) flight animals showed an increase of autophagy and apoptosis, while duct cells contained vacuoles with endocytosed proteins. In STS-135, decreases were seen in the regulatory subunit of type II protein kinase A (RII) by Western blotting, and demilune cell and parotid protein (DCPP) and α-amylase (p<0.01) by immunogold labeling, while proline-rich proteins (PRPs, p<0.001) and parotid secretory protein (PSP, p<0.05) were increased. These results suggest microgravity effects on secretion are function-dependent. Microarray analyses showed significant changes in the expression of a number of genes, including components of the cyclic-3’,5’,-adenosine monophosphate (cyclic AMP) signaling pathway. Compared to habitat ground controls, mice from both flights exhibited altered expression of cyclic AMP-specific phosphodiesterases, adenylate cyclase isoforms, and several A-kinase anchoring proteins. Bion-M1 flight mice showed increases in gene expression for lysozyme and amylase, a decrease in PRPs, and RII expression was unchanged from control values. Secretory protein expression is altered by travel in space, representing a reversible adjustment to microgravity conditions. Ultimately, the goal is to develop a test kit using saliva — an easily obtained body fluid — to assess the physiologic effects of travel in space.
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