Fluorescent Probes of Tissue Transglutaminase Reveal Its Association with Arterial Stiffening

被引：21

作者：

Chabot, Nicolas ^{[1
]}

Moreau, Simon ^{[2
]}

Mulani, Amina ^{[1
]}

Moreau, Pierre ^{[2
]}

Keillor, Jeffrey W. ^{[1
]}

机构：

[1] Univ Montreal, Dept Chim, Montreal, PQ H3C 3J7, Canada

[2] Univ Montreal, Fac Pharm, Montreal, PQ H3C 3J7, Canada

来源：

CHEMISTRY & BIOLOGY | 2010年 / 17卷 / 10期

基金：

加拿大自然科学与工程研究理事会;

关键词：

PIG LIVER TRANSGLUTAMINASE; MATRIX GLA-PROTEIN; CROSS-LINKING; ALPHA; BETA-UNSATURATED AMIDES; IRREVERSIBLE INHIBITORS; SELECTIVE INHIBITORS; IN-VITRO; MODEL; CALCIFICATION; EXPRESSION;

D O I：

10.1016/j.chembiol.2010.06.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Tissue transglutaminase (TG2) catalyzes the cross-linking of proteins TG2 has been implicated in fibrosis and vascular calcification, both of which lead to a common feature of aging known as arterial stiffness In order to probe the role of TG2 in arterial rigidification, we have prepared a fluorescent irreversible inhibitor as a probe for TG2 activity (RhodB-PGG-K(Acr)-LPF-OH) This probe was synthesized on solid support, characterized kinetically (K-inact = 0 68 min(-1), K-1 = 79 mu M), and then used to stain the aorta from rats used as a model of isolated systolic hypertension (ISH) Interestingly, TG2 activity was thus shown to increase over 4 weeks of the hypertension model, corresponding with the previously observed increase in arterial stiffness These results clearly suggest an association between TG2 and the phenomenon of arterial rigidification

引用

页码：1143 / 1150

页数：8

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