Sciatin: a myotrophic protein increases the number of acetylcholine receptors and receptor clusters in cultured skeletal muscle.
Sciatin: a myotrophic protein increases the number of acetylcholine receptors and receptor clusters in cultured skeletal muscle.
复制标题
Sciatin：一种肌营养蛋白，可增加培养骨骼肌中乙酰胆碱受体和受体簇的数量。
DOI：
10.1016/0012-1606(82)90324-4
复制
发表时间：
1982
影响因子：
2.7
通讯作者：
Guth,L
中科院分区：
文献类型：
--
作者：
Markelonis,GJ;Oh,TH;Eldefrawi,ME;Guth,L
其他人已经证明，神经提取物或神经元条件培养基中存在的因子可以增加胚胎骨骼肌培养物中乙酰胆碱受体（AChR）的数量和受体簇的数量。我们最近发现，糖蛋白，sciatin，在体外对发育中的肌肉有营养作用。在本研究中，我们研究了sciatin对鸡骨骼肌AChRs的影响。结果表明，在分化的肌细胞中，用~（125）I-α-银环蛇毒素（α-Btx）结合法测定的AChR/皿数和乙酰胆碱酯酶（AChE）活性均显著增加。乙酰胆碱受体的增加引起的sciatin是由于增加受体的合成和掺入。乙酰胆碱受体的合成速率在坐骨神经素处理的培养物中高达对照速率的5倍，并且被放线菌酮（10 μM）显著降低。AChR降解不受肌营养蛋白的影响。虽然在肌生成过程中，sciatin增加了AChR/皿的数量，但AChR比活性（以皮摩尔125 I-α-Btx结合/mg细胞蛋白表示）仅被肌营养蛋白短暂增加。这与乙酰胆碱酯酶的比活性在sciatin处理的文化，保持整个分化升高。125 I-α-Btx标记的培养物的放射自显影显示，sciatin引起AChR“热点”的数量和大小增加，并在神经肌肉培养物中保持这些AChR簇的完整性长达5周。此时，对照培养物已完全退化。的机制，其中sciatin增强AChRs的合成似乎是不同的河豚毒素（TTX），一种药剂，废除肌肉活动。然而，像茶碱一样，由于肌营养蛋白增加细胞和条件培养基中的cAMP，因此sciatin可能通过调节环AMP引起AChRs合成增加。本研究的结果表明，sciatin可能与其他人描述的运动神经元的扩散因子有关，该扩散因子对AChRs具有营养作用。此外，我们认为，这种肌营养蛋白可能是负责集群的乙酰胆碱受体和维持受体簇在神经肌肉接头在发展中的鸟类肌肉。
Factors present in neural extracts or in media conditioned by neurons have been shown by others to increase both the number of acetylcholine receptors (AChRs) and the number of receptor clusters in cultures of embryonic skeletal muscle. We have recently shown that the glycoprotein,sciatin, exerts trophic effects on developing musclein vitro. In the present study, we investigated the effect of sciatin on AChRs in aneural cultures of chick skeletal muscle. Sciatin caused a significant increase in the number of AChRs/dish as measured by binding of125I-α-bungarotoxin (α-Btx) and in acetylcholinesterase (AChE) activity/dish in differentiating muscle cells. The increase in AChRs elicited by sciatin was due solely to increased receptor synthesis and incorporation. The rate of AChR synthesis in sciatin-treated cultures was as much as five times the control rate and was significantly reduced by cycloheximide (10 μM). AChR degradation was unaffected by the myotrophic protein. Although the number of AChRs/dish was increased by sciatin during myogenesis, AChR specific activity, expressed as picomoles125I-α-Btx bound/mg cell protein, was only transiently increased by the myotrophic protein. This contrasted with AChE specific activity in sciatin-treated cultures which remained elevated throughout differentiation. Autoradiographs of125I-α-Btx-labeled cultures showed that sciatin caused an increase in the number and size of AChR “hot spots” and maintained the integrity of these AChR clusters in aneural muscle cultures for up to 5 weeks. At this time control cultures had completely degenerated. The mechanism by which sciatin enhanced the synthesis of AChRs appeared to be distinct from that of tetrodotoxin (TTX), an agent which abolishes muscle activity. However, like theophylline, sciatin might evoke increased synthesis of AChRs via regulation of cyclic AMP since the myotrophic protein increased cAMP both in cells and in conditioned medium. The results of this study suggest that sciatin may be related to the diffusible factor(s) from motor neurons described by others which has trophic effects on AChRs. Furthermore, we suggest that this myotrophic protein may be responsible for the clustering of AChRs and maintenance of receptor clusters at neuromuscular junctions in developing avian muscle.