Interleukin-1 stimulates catabolism in C2C12 myotubes
Interleukin-1 stimulates catabolism in C2C12 myotubes
复制标题
DOI：
10.1152/ajpcell.00626.2008
复制
发表时间：
2009-09-01
影响因子：
5.5
通讯作者：
Reid, Michael B.
中科院分区：
文献类型：
--
作者：
Li, Wei;Moylan, Jennifer S.;Reid, Michael B.
李伟，张建军，张建军，张建军。白细胞介素-1对肌管分解代谢的影响。[J] .中国生物医学工程学报，2009,31(4):559 - 564。首次发表于2009年7月22日；doi: 10.1152 / ajpcell.00626.2008。-白细胞介素-1 （IL-1）是一种炎症细胞因子，与肌肉分解代谢有关，肌肉分解代谢是由泛素-蛋白酶体途径的肌肉特异性E3蛋白调节的过程。为了解决细胞机制，我们验证了IL-1通过直接作用于肌肉增加两个关键E3蛋白atrogin1/muscle atrophy F-box （MAFbx）和muscle RING-finger 1 （MuRF1）的表达来诱导肌原纤维蛋白损失的假设。实验采用成熟的C2C12肌管，以消除全身细胞因子的影响，避免非肌肉细胞类型的旁分泌信号。时间过程协议被用来定义细胞反应的顺序。我们发现肌管暴露于IL-1 α或IL-1 α后60-120分钟atrogin1/MAFbx mRNA和MuRF1 mRNA升高。这些反应之前有促进E3表达的信号事件。两种IL-1亚型均刺激p38丝裂原活化蛋白激酶的磷酸化和核因子κ B （nf - κ B）信号传导；I-kappa B水平下降，NF-kappa B DNA结合活性增加。其他E3表达的调节因子不受IL-1[胞质氧化活性，叉头o （Foxo）活性]的影响，或产生矛盾反应（AKT）。慢性暴露于C2C12肌管超过48小时，导致肌管宽度减小和肌动蛋白损失。我们得出结论，IL-1 α和IL-1 β通过氧化剂和AKT/ foxo不依赖的机制激活p38 MAPK，刺激NF-kappa B信号，增加atrogin1/MAFbx和MuRF1的表达，并减少分化肌管中的肌原纤维蛋白。
Li W, Moylan JS, Chambers MA, Smith J, Reid MB. Interleukin-1 stimulates catabolism in C2C12 myotubes. Am J Physiol Cell Physiol 297: C706-C714, 2009. First published July 22, 2009; doi:10.1152/ajpcell.00626.2008.-Interleukin-1 (IL-1) is an inflammatory cytokine that has been linked to muscle catabolism, a process regulated by muscle-specific E3 proteins of the ubiquitin-proteasome pathway. To address cellular mechanism, we tested the hypothesis that IL-1 induces myofibrillar protein loss by acting directly on muscle to increase expression of two critical E3 proteins, atrogin1/muscle atrophy F-box (MAFbx) and muscle RING-finger 1 (MuRF1). Experiments were conducted using mature C2C12 myotubes to eliminate systemic cytokine effects and avoid paracrine signaling by nonmuscle cell types. Time-course protocols were used to define the sequence of cellular responses. We found that atrogin1/MAFbx mRNA and MuRF1 mRNA are elevated 60-120 min after myotube exposure to either IL-1 alpha or IL-1 alpha. These responses are preceded by signaling events that promote E3 expression. Both IL-1 isoforms stimulate phosphorylation of p38 mitogen-activated protein kinase and stimulate nuclear factor-kappa B (NF-kappa B) signaling; I-kappa B levels fall and NF-kappa B DNA binding activity increases. Other regulators of E3 expression are unaffected by IL-1 [ cytosolic oxidant activity, Fork-head-O (Foxo) activity] or respond paradoxically (AKT). Chronic exposure of C2C12 myotubes over 48 h resulted in reduced myotube width and loss of sarcomeric actin. We conclude that IL-1 alpha and IL-1 beta act via an oxidant-and AKT/Foxo-independent mechanism to activate p38 MAPK, stimulate NF-kappa B signaling, increase expression of atrogin1/MAFbx and MuRF1, and reduce myofibrillar protein in differentiated myotubes.