Lelkes P I, Ramos E M, Chick D M, Liu J, Unsworth B R
Department of Medicine, University of Wisconsin Medical School, Milwaukee 53201.
FASEB J. 1994 Nov;8(14):1177-82. doi: 10.1096/fasebj.8.14.7958625.
During spaceflight, alterations in blood and urinary catecholamine (CA) levels have been observed, yet the cellular/molecular mechanisms leading to these changes are not known. We used molecular, immunological, and biochemical approaches to analyze in situ the expression of catecholamine enzymes in adrenal medullary chromaffin cells of rats flown for 6 days on board Space Shuttle mission STS-54. Exposure to microgravity (10(-6) g) resulted in a 35% inhibition of both the expression and the specific activity of tyrosine hydroxylase (TH), the rate-limiting step in the cascade of CA synthesis. By contrast, the expression, specific activity, and immunoreactivity of other catecholamine-synthesizing enzymes, e.g., phenylethanolamine-N-methyl-transferase (PNMT), were not altered. The total tissue CA contents were reduced, concomitant with a decrease in the epinephrine:norepinephrine ratio. These results are in line with reports of other gravity-sensitive cellular effects and suggest that the inhibition of TH expression might be due to a direct effect of microgravity on PKC-dependent signal transduction pathways in chromaffin cells.
在太空飞行期间，已观察到血液和尿液中儿茶酚胺（CA）水平的变化，但导致这些变化的细胞/分子机制尚不清楚。我们使用分子、免疫和生化方法，对搭乘航天飞机任务STS - 54飞行6天的大鼠肾上腺髓质嗜铬细胞中儿茶酚胺酶的表达进行原位分析。暴露于微重力（10^(-6) g）导致酪氨酸羟化酶（TH）的表达和比活性均受到35%的抑制，TH是CA合成级联反应中的限速步骤。相比之下，其他儿茶酚胺合成酶，如苯乙醇胺 - N - 甲基转移酶（PNMT）的表达、比活性和免疫反应性并未改变。总组织CA含量降低，同时肾上腺素与去甲肾上腺素的比值下降。这些结果与其他重力敏感细胞效应的报道一致，并表明TH表达的抑制可能是由于微重力对嗜铬细胞中PKC依赖的信号转导途径的直接作用。
