Inhibitory effect of human α_2-plasmin inhibitor and it's intensified compound by S-nitrosylation on the activity of arginine-specific cysteine proteinase from Porphyromonas gingivalis.

应用荧光底物研究了人α_2-纤溶酶抑制物(α_2pi)和S硝化α_2-纤溶酶抑制物(S-NO-α_2pi)对成人牙周炎病原菌牙龈卟啉单胞菌精氨酸特异性半胱氨酸蛋白酶活性的影响。我们发现人α_2pi和S-NO-α_2pi对RGP有抑制作用，且呈剂量依赖关系。α_2pi是丝氨酸蛋白家族的成员之一，是典型的丝氨酸蛋白酶纤溶酶的特异性抑制因子。然而，有关体液因子，如α_1-蛋白酶抑制剂或α_2-巨球蛋白对半胱氨酸蛋白酶尤其是RGP的抑制作用的研究报道较少。在本研究中，我们发现了α_2pi作为一种有效的Rgp抑制剂的新功能。S硝基衍生物对人纤溶酶和Rgp的抑制活性略高于完整的α_2pi。这些结果有力地表明，S-NO-α_2pi是预防牙龈假单胞菌毒力的有效工具。

We investigated the effect of human α_2-plasmin inhibitor (α_2PI) and S-nitrosylated α_2-plasmin inhibitor (S-NO-α_2PI) on the activity of arginine-specific cysteine proteinase (gingipain, RGP) from Porphyromonas gingivalis, an aetiological bacterium of adult periodontitis, with the use of fluorogenic substrates. We discovered that human α_2PI as well as S-NO-α_2PI play a inhibitory effect to the RGP in a dose-dependent manner. The α_2PI, one of the members of serpin family, is well known as a specific inhibitor of plasmin, a typical serine proteinase. However, few studies have been reported concerning the inhibitory potency of humoral factors, such as α_1-protease inhibitor or α_2-macroglobulin, against cysteine proteinases especially RGP. In this study, we found a novel function of α_2PI as a potent inhibitor of RGP. The inhibitory potencies of the S-nitrosylated derivative against both human plasmin and RGP were slightly higher than those of the intact α_2PI. These results strongly suggest that S-NO-α_2PI is a useful tool for preventing the virulence of P. gingivalis.