Laminin-1 and the RKRLQVQLSIRT laminin-1 alpha1 globular domain peptide stimulate matrix metalloproteinase secretion by PC12 cells.
Laminin-1 and the RKRLQVQLSIRT laminin-1 alpha1 globular domain peptide stimulate matrix metalloproteinase secretion by PC12 cells.
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Laminin-1 和 RKRLQVQLSIRT laminin-1 alpha1 球状结构域肽刺激 PC12 细胞分泌基质金属蛋白酶。
DOI：
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发表时间：
1998
影响因子：
3.7
通讯作者：
H. Kleinman
中科院分区：
文献类型：
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作者：
B. Weeks;M. Nomizu;R. Ramchandran;Y. Yamada;H. Kleinman
在这里，我们研究了层粘连蛋白-1 和特定层粘连蛋白-1 衍生的合成肽刺激神经元细胞基质金属蛋白酶分泌的能力。对经层粘连蛋白 1 处理的 PC12 和 NG108-15 细胞的条件培养基进行酶谱分析，发现未经处理的细胞不分泌一种 72 kDa 的基质金属蛋白酶。 Laminin-1 α1 链衍生的合成肽 AASIKVAVSADR (LAM-L) 和 RKRLQVQLSIRT (AG-73) 也刺激 PC12 细胞分泌 72 kDa 基质金属蛋白酶。我们使用一系列单氨基酸被丙氨酸取代的 AG-73 类似物，进一步研究了 AG-73 对细胞附着、神经突生长和基质金属蛋白酶分泌的结构要求。在测试的底物水平上，AG-73 肽促进了 67% 的 PC12 细胞的粘附和 71% 的 PC12 细胞的神经突生长。中央 LQVQ 序列内任何一个氨基酸的取代都会导致细胞附着的大幅减少，而羧基末端近端氨基酸 L、S 和 R 的取代对附着几乎没有影响。任何氨基末端近端 LQV 氨基酸和羧基末端 L、I 和 R 残基的丙氨酸取代导致神经突生长减少 65-91%。这些数据表明，细胞附着和神经突生长的序列要求不一定是耦合的，但神经突生长和基质金属蛋白酶分泌的序列要求是相同的。我们得出结论，laminin-1 能够刺激神经元细胞分泌基质金属蛋白酶。此外，这项研究还鉴定出 LQVXLXIR 层粘连蛋白-1 α1 球状结构域肽能够刺激神经突生长和基质金属蛋白酶分泌。
Here we have investigated the ability of laminin-1 and specific laminin-1-derived synthetic peptides to stimulate neuronal cell matrix metalloproteinase secretion. Zymographic analysis of conditioned media from laminin-1-treated PC12 and NG108-15 cells revealed a 72-kDa matrix metalloproteinase which was not secreted by untreated cells. Laminin-1 alpha1 chain-derived synthetic peptides, AASIKVAVSADR (LAM-L) and RKRLQVQLSIRT (AG-73), also stimulated PC12 cell secretion of a 72-kDa matrix metalloproteinase. We further investigated the structural requirements of AG-73 for cell attachment, neurite outgrowth, and matrix metalloproteinase secretion using a series of AG-73 analogs that had single amino acids substituted with alanine. At the substrate levels tested, the AG-73 peptide promoted the adhesion of 67% of the PC12 cells and neurite outgrowth in 71% of the PC12 cells. Substitutions in any one of the amino acids within the central LQVQ sequence resulted in a large reduction in cell attachment whereas substitution in the carboxyl terminal proximal amino acids L, S, and R had little effect on attachment. Alanine substitution of any of the amino terminal proximal LQV amino acids and the carboxyl terminal L, I, and R residues resulted in a 65-91% reduction in neurite outgrowth. These data demonstrate that the sequence requirements for cell attachment and neurite outgrowth were not necessarily coupled but that the sequence requirements for neurite outgrowth and matrix metalloproteinase secretion were identical. We conclude that laminin-1 is able to stimulate neuronal cells to secrete a matrix metalloproteinase. Further, this study identifies the LQVXLXIR laminin-1 alpha1 globular domain peptide to be capable of stimulating both neurite outgrowth and matrix metalloproteinase secretion.
神经突渗透到胶原蛋白凝胶中需要 Ca2 依赖性金属蛋白酶活性。
影响因子：
2.9
作者：
Pittman,RN;Williams,AG
通讯作者：
Williams,AG