Arterial vimentin is a transglutaminase substrate: A link between vasomotor activity and remodeling?
Arterial vimentin is a transglutaminase substrate: A link between vasomotor activity and remodeling?
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DOI：
10.1159/000102277
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发表时间：
2007-01-01
影响因子：
1.7
通讯作者：
Sane, David C.
中科院分区：
文献类型：
--
作者：
Gupta, Madhu;Greenberg, Charles S.;Sane, David C.
背景/目的：转谷氨酰胺酶（TG2和因子XIIIa）可能通过交联多种底物（包括细胞外基质蛋白和蛋白酶抑制剂）来促进动脉的稳定性。然而，优选的底物尚未确定。方法：我们使用胺供体5-生物胺氨基戊基胺，它与受体谷氨酰胺残基共价连接，以确定颈动脉内膜切除术组织中的谷氨酰胺转酶底物。结果：5-生物胺酰胺戊基胺的掺入是钙依赖的，导致一些蛋白质被链霉亲和素过氧化物酶检测并通过单体亲和素亲和柱纯化。对从色谱柱中洗脱的42 kDa的主要条带以及另外两个条带（80和65 kDa）进行测序，分别揭示了蛋白蛋白、转铁蛋白和白蛋白的内部片段。5个颈动脉斑块匀浆中有5个检测到维门汀二聚体。结论：静脉溶栓蛋白是谷氨酰胺转胺酶的主要动脉底物。先前已经证明TG2活性和vimentin有助于动脉的血管舒缩活性。此外，谷氨酰胺转酶（TG2和XIIIa因子）以及vimentin调节低流量状态下发生的结构改变（向内重塑）。转谷氨酰胺酶介导的静脉蛋白二聚化产生了一种新的统一途径，通过该途径可以调节血管舒张和重构反应。
Background/ Aims: The transglutaminases ( TG2 and factor XIIIa) may contribute to the stability of arteries by cross-linking a variety of substrates, including extracellular matrix proteins and protease inhibitors. The preferred substrates have never been determined, however. Methods: We used an amine donor, 5-biotinamidopentylamine, that is covalently linked to acceptor glutamine residues, to determine transglutaminase substrates in carotid endarterectomy tissue. Results: The incorporation of 5-biotinamidopentylamine was calcium dependent, resulting in the labeling of several proteins that were detected by streptavidin-peroxidase and purified over a monomeric avidin affinity column. A major band of 42 kDa that was eluted from the column was sequenced along with 2 additional bands ( 80 and 65 kDa), revealing an internal fragment of vimentin, transferrin and albumin, respectively. Vimentin dimers were detected in 5 out of 5 carotid plaque homogenates. Conclusions: Vimentin is a major arterial substrate for transglutaminases. It has previously been shown that TG2 activity and vimentin contribute to vasomotor activity of arteries. Furthermore, transglutaminases ( both TG2 and factor XIIIa), as well as vimentin, regulate structural alterations ( inward remodeling) that occur in response to low flow states. Transglutaminase-mediated vimentin dimerization produces a novel unifying pathway by which vasodilatory and remodeling responses may be regulated.