Aronson D, Wojtaszewski J F, Thorell A, Nygren J, Zangen D, Richter E A, Ljungqvist O, Fielding R A, Goodyear L J
Research Division, Joslin Diabetes Center, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02215, USA.
Am J Physiol. 1998 Aug;275(2):C555-61. doi: 10.1152/ajpcell.1998.275.2.C555.
The mitogen-activated protein (MAP) kinase signaling pathways are believed to act as critical signal transducers between stress stimuli and transcriptional responses in mammalian cells. However, it is not known whether these signaling cascades also participate in the response to injury in human tissues. To determine whether injury to the vastus lateralis muscle activates MAP kinase signaling in human subjects, two needle biopsies or open muscle biopsies were taken from the same incision site 30-60 min apart. The muscle biopsy procedures resulted in striking increases in dual phosphorylation of the extracellular-regulated kinases (ERK1 and ERK2) and in activity of the downstream substrate, the p90 ribosomal S6 kinase. Raf-1 kinase and MAP kinase kinase, upstream activators of ERK, were also markedly stimulated in all subjects. In addition, c-Jun NH2-terminal kinase and p38 kinase, components of two parallel MAP kinase pathways, were activated following muscle injury. The stimulation of the three MAP kinase cascades was present only in the immediate vicinity of the injury, a finding consistent with a local rather than systemic activation of these signaling cascades in response to injury. These data demonstrate that muscle injury induces the stimulation of the three MAP kinase cascades in human skeletal muscle, suggesting a physiological relevance of these protein kinases in the immediate response to tissue injury and possibly in the initiation of wound healing.
丝裂原活化蛋白（MAP）激酶信号通路被认为是哺乳动物细胞中应激刺激与转录反应之间的关键信号转导者。然而，尚不清楚这些信号级联反应是否也参与人体组织对损伤的反应。为了确定股外侧肌损伤是否会激活人体受试者的MAP激酶信号，在相隔30 - 60分钟的时间里，从同一切口部位进行了两次针吸活检或开放性肌肉活检。肌肉活检程序导致细胞外调节激酶（ERK1和ERK2）的双重磷酸化以及下游底物p90核糖体S6激酶的活性显著增加。ERK的上游激活剂Raf-1激酶和MAP激酶激酶在所有受试者中也受到明显刺激。此外，在肌肉损伤后，两个平行MAP激酶途径的组成部分c-Jun氨基末端激酶和p38激酶也被激活。这三种MAP激酶级联反应的刺激仅出现在损伤部位附近，这一发现与这些信号级联反应在响应损伤时的局部而非全身激活相一致。这些数据表明，肌肉损伤会诱导人体骨骼肌中三种MAP激酶级联反应的刺激，提示这些蛋白激酶在对组织损伤的即时反应以及可能在伤口愈合起始过程中具有生理相关性。
