Proteomic Profiling of Growth Hormone-Responsive Proteins in Human Peripheral Blood Leukocytes
Proteomic Profiling of Growth Hormone-Responsive Proteins in Human Peripheral Blood Leukocytes
复制标题
DOI：
10.1210/jc.2009-0778
复制
发表时间：
2009-08-01
影响因子：
5.8
通讯作者：
Baxter, Robert C.
中科院分区：
文献类型：
--
作者：
Chung, Liping;Nelson, Anne E.;Baxter, Robert C.
内容：GH是一种已知的免疫系统调节剂，但外源性GH给药对白色血细胞蛋白的影响尚未研究。表面增强激光解吸电离飞行时间质谱SELDI-TOF MS是研究GH对免疫系统蛋白质影响的有力平台。目的：我们的目标是探索一种新的方法，通过SELDI-TOF MS蛋白质组学分析检测人白细胞中GH反应蛋白。设计：我们进行了一项随机、双盲、安慰剂对照的GH给药研究，治疗8周，随后洗脱6周。来自30名受试者的治疗前和治疗后样本用于生物标志物发现。设置：该研究在临床研究机构进行。参与者：我们研究了30名接受娱乐训练的健康运动员。干预：受试者接受重组人GH（2 mg/d sc; n = 22）或安慰剂（n = 8）治疗8 wk。采用CM 10弱阳离子交换蛋白芯片进行蛋白质组学分析，并对GH调控蛋白进行纯化，通过质谱和/或免疫印迹进行鉴定。SELDI-TOF分析揭示了一些GH调节的肽/蛋白在3- 22 kDa的范围内，无论是向上或向下调节的GH。其中几个可能是有用的生物标志物生长激素的行动。钙结合，促炎calgranulin S100 A8，S100 A9，和S100 A12都显着下调GH treatment.Conclusion：这项研究说明了新的使用人类白细胞蛋白质组学分析SELDI-TOF MS，并揭示了促炎S100蛋白质的负调控GH在人类白色血细胞。（临床内分泌代谢杂志94：3038-3043，2009）
Context: GH is a known modulator of the immune system, but the effect of exogenous GH administration on white blood cell proteins has not been investigated. Surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) is a powerful platform for the study of GH effects on immune system proteins.Objective: Our objective was to explore a novel approach for the detection of GH-responsive proteins in human leukocytes by proteomic analysis using SELDI-TOF MS.Design: We conducted a randomized double-blind, placebo-controlled GH administration study of 8 wk treatment followed by 6 wk washout. Pre- and posttreatment samples from 30 subjects were used for biomarker discovery.Setting: The study was performed at a clinical research facility.Participants: We studied 30 recreationally trained healthy athletes.Intervention: Subjects received either recombinant human GH (2 mg/d sc; n = 22) or placebo (n = 8) for 8 wk.Main Outcome Measures: Proteomic profiles were determined using CM10 weak cation-exchange protein chips, and some GH-regulated proteins were purified and identified by mass spectrometry and/or immunoblotting.Results: SELDI-TOF analysis revealed a number of GH-regulated peptides/proteins in the 3- to 22-kDa range that are either up-or down-regulated by GH. Several of these may be useful as biomarkers of GH action. The calcium-binding, proinflammatory calgranulins S100A8, S100A9, and S100A12 were all significantly down-regulated in response to GH treatment.Conclusion: This study illustrates the novel use of human leukocyte proteomic profiling by SELDI-TOF MS and reveals the negative regulation of proinflammatory S100 proteins by GH in human white blood cells. (J Clin Endocrinol Metab 94: 3038-3043, 2009)