Activation of blood coagulation factor IX by gingipains R, arginine-specific cysteine proteinases from Porphyromonas gingivalis.
Activation of blood coagulation factor IX by gingipains R, arginine-specific cysteine proteinases from Porphyromonas gingivalis.
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牙龈蛋白酶 R（牙龈卟啉单胞菌的精氨酸特异性半胱氨酸蛋白酶）激活凝血因子 IX。
作者：
Takahisa Imamura;Sumio Tanase;Takayoshi Hamamoto;J. Potempa;James Travis
研究了来自牙龈卟啉单胞菌的两种精氨酸特异性半胱氨酸蛋白酶（gingipains R）（成人牙周炎的病因因子）在激活因子IX（因子IXa）的活性增强剂乙二醇存在下对人因子IX（因子IXa）活性的影响，并使用荧光寡肽底物。每个gingipain R都能快速激活因子IX，但含有血凝素/粘附和催化结构域的95 kDa蛋白酶复合物（HRgpA）比只有催化结构域的50 kDa单链gingipain R （RgpB）效率高2.4倍。因子IX消化片段的SDS/PAGE和n端序列分析表明，与所有内源性激活剂一样，gingipains R也通过IXa中间体产生因子IXabeta。值得注意的是，磷脂以Ca（2+）依赖的方式增强HRgpA而不是RgpB对因子IX的激活。在这两个辅助因子存在的情况下，HRgpA对激活因子IX (k(cat))/ k(m)的动力学效率=1.9x10(6) m（-1）。s(-1))比RgpB (k(cat)/ k(m)=2.3 × 10（5) m(-1)）高8.5倍。s(-1))，是viia -组织因子复合物的2倍，但比XIa因子低8倍。比较HRgpA对血浆中因子IX、因子X和凝血酶原的相对激活率，表明牙龈蛋白酶R对因子IX的转化有显著贡献。综上所述，牙龈蛋白酶R是首次报道的细菌源因子IX的激活剂。通过这种作用，它们可能参与凝血酶的产生，以及随后产生的前列腺素和白细胞介素1，所有这些都被发现与牙周炎的发生和发展有关。
The effect of two arginine-specific cysteine proteinases (gingipains R) from Porphyromonas gingivalis, an aetiological factor of adult periodontitis, on the activation of human factor IX was investigated in the presence of ethylene glycol, an activity enhancer of activated factor IX (factor IXa), with the use of a fluorogenic oligopeptide substrate. Each gingipain R rapidly activated factor IX but the 95 kDa proteinase complex (HRgpA) that contains both haemagglutinin/adhesion and catalytic domains was 2.4-fold more efficient than the single-chain 50 kDa gingipain R (RgpB), which has only a catalytic domain. SDS/PAGE and N-terminal sequence analysis of factor IX digestion fragments indicated that, like all endogenous activators, gingipains R also produce factor IXabeta via an IXa intermediate. Significantly, phospholipids augmented the activation of factor IX by HRgpA but not by RgpB in a Ca(2+)-dependent manner. In the presence of both cofactors the kinetic efficiency of HRgpA to activate factor IX (k(cat)/K(m)=1.9x10(6) M(-1).s(-1)) was 8.5-fold higher than that of RgpB (k(cat)/K(m)=2.3x10(5) M(-1).s(-1)) and double that of the factor VIIa-tissue factor complex, but 8-fold lower than that for factor XIa. A comparison of the relative activation rates of factor IX, factor X and prothrombin directly in plasma by HRgpA suggests a significant contribution for factor IX conversion in blood coagulation induced by gingipains R. Taken together, gingipains R are the first-reported activators of factor IX of bacterial origin. By this effect they could be involved in the production of thrombin as well as the subsequent generation of prostaglandins and interleukin 1, all of which have been found to be associated with the development and progression of periodontitis.
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影响因子：
2.9
作者：
DAVIE, EW;FUJIKAWA, K;KISIEL, W
通讯作者：
KISIEL, W
影响因子：
56.9
作者：
HOLT, SC;EBERSOLE, J;KORNMAN, KS
通讯作者：
KORNMAN, KS
XIa 因子催化激活人凝血因子 IX 的动力学。
DOI：
10.1172/jci111343
发表时间：
1984
期刊：
The Journal of clinical investigation
影响因子：
--
作者：
Walsh,PN;Bradford,H;Sinha,D;Piperno,JR;Tuszynski,GP
通讯作者：
Tuszynski,GP
DOI：
10.1016/s0021-9258(18)42587-2
发表时间：
1992-04
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
E. J. Duffy;P. Lollar
通讯作者：
E. J. Duffy;P. Lollar
吲哚美辛抑制凝血酶刺激的胎鼠肢骨吸收，但不抑制甲状腺素刺激的吸收。
DOI：
10.1016/0090-6980(86)90168-1
发表时间：
1986
期刊：
Prostaglandins
影响因子：
--
作者：
Hoffmann,O;Klaushofer,K;Koller,K;Peterlik,M;Mavreas,T;Stern,P
通讯作者：
Stern,P