新发现的SOCS蛋白家族:揭示了创伤和营养不良时代谢异常的机理

A newly identified SOCS protein family: one of the mechanisms of metabolic changes during stress and malnutrition in vivo

细胞因子信号传递抑制体（SOCS）是一组新近才被认识的蛋白，它们经细胞因子诱导而释放，再反馈抑制细胞因子在细胞内的信号传递。以往的工作显示：内毒素能显著提高SOCS在大鼠肝脏中的表达，这又同内毒素引起的生长激素的拮抗密切相关。目的探明SOCS基因在营养不良（饥饿）状态下在不同组织中的反应。方法雄性S-D大鼠（～200g）分别受饥饿1、2、3天，另一组在饥饿3天后重新进食3天。用Northemblotting检测肝脏和肌肉中的mRNA水平，其中所用的cDNA探针为Joslin研究中心所克隆。结果在一天禁食后，鼠肝脏中的SOCS-3mRNA出现了进行性的增高，至禁食3天其值高于原来的一倍，而SOCS-2mRNA却在同时下降了75％。重新进食3天后，SOCS－2和SOCS-3重新恢复到正常水平。细胞内信号传递蛋白STAT1、STAT3、STAT5a和STAT5b均无酪氨酸磷酸化反应，MAP激酶中的ERK1、ERK2、P3S、JUNK1，JUNK2均无激活表现。在肌肉中，3天的禁食使SOCS-2mRNA有类似上述的75％的下降，而SOCS-3mRNA却无任何改变。结果提示，营养不良能以不同的方式调节SOCS－2和SOCS-3，这种调节是组织特异性的，SOCSmRNA的变化看来并非由于各种STAT的磷酸化和MAP激酶的激活而造成。结论在饥饿状态下。

Suppressor of cytokine sigaling (SOCS) genes encode a family of protein recently identified as negative feedback inhibitors of signaling by cytokine receptors. We have previously shown that endotoxin markedly stimulates SOCS gene expression in rat liver, that correlates with observed resistance to growth hortnone signaling during endotoxemia. The objective of this study was to determine the expression of SOCS genes in state of fasting that have been shown to cause altered responses in pro-inflammatory cytokines and anabolic hormones. Male Sprague-Dawley rats (~200g) were fasted for 1, 2 or 3 days, or refed for 3 days following a 3-day period of fasting. Liver and muscle mRNAs were determined by Northern blotting using specific rat cDNA probes cloned in our laboratory. In liver,afte a 1-day lag petiod,there was a progressive 2-fold increase in SOCS-3 and 75 % decrease in m2 mRNA afte 2 and 3 of fasting. Both SOCS mRNAs were normalized by 3 days of refeeding. There was no measurable changes in tyrosine phosphorylation of STAT1,STAT3, STAT5a or STAT5b, nor activation of MAP kinases including ERK 1 /2, p38, and JUNK 1/2 in liver by 3 days of fasting. In muscle,there was a similar 75 % decrease in SOCS-2 mRNA, but no change in SOCS-3 mRNA following 3 days of fasting.These data suggest that malnutrition regulates SOCS-2 and SOCS-3 in a different way, and this regulation is tissue specific. The changes of SOCS mRANs are independent of measurable phosphorylation of multiple STATs and activation of MAP kinases. The altered SOCS expressions during fasting may explain the changes of biological effects of multiple cytokines and anabolic hormones in malnutrition states.