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Encouraging and supporting smoking cessation in the workforce

机译：鼓励和支持员工戒烟

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SMTP-7 is a small molecule that promotes the proteolytic activation of plasminogen by relaxing its conformation. SMTP-7 has excellent therapeutic activities against thrombotic stroke in several rodent models. The objective of this study was to elucidate detailed mechanism of the action of SMTP-7 in vitro. We report here that the action of SMTP-7 requires a cofactor with a long-chain alkyl or alkenyl group, and that the fifth kringle domain (kringle 5) of plasminogen is involved in the SMTP-7 action. In this study, we found that the SMTP-7 action to enhance plasminogen activation depended on the presence of a certain type of surfactant, and we screened biologically relevant molecules for their cofactor activity for the SMTP action. As a result, phospholipids, sphingolipids, and oleic acid were found to be active in assisting the SMTP-7 action. On the contrary, stearic acid and bile acids were inactive. Thus, a certain structural element, not only the surface-activating potential, is required for a compound to act as a cofactor for the SMTP-7 action. The plasminogen molecule consists of a PAN domain, five kringle domains, and a serine protease domain. The cofactor-dependent effects of SMTP-7 was observed with plasminogen species including kringle 5 such as intact plasminogen (Glu-plasminogen), des-PAN plasminogen (Lys-plasminogen), and des-[PAN-(kringles 1-4)] plasminogen (mini-plasminogen). However, SMTP-7 effect was not observed with the smallest plasminogen species des-[PAN-(kringles 1-4) and a half of kringle 5)] plasminogen (micro-plasminogen). Thus, kringle 5 is crucial for the action of SMTP-7.
机译：SMTP-7是一个小分子，可通过放松其构象来促进纤溶酶原的蛋白水解活化。在一些啮齿动物模型中，SMTP-7具有出色的抗血栓性中风的治疗活性。这项研究的目的是阐明SMTP-7体外作用的详细机制。我们在这里报告SMTP-7的作用需要具有长链烷基或烯基的辅因子，并且纤溶酶原的第五个kringle域（kringle 5）参与了SMTP-7的作用。在这项研究中，我们发现SMTP-7增强纤溶酶原激活的作用取决于某种类型的表面活性剂的存在，并且我们针对SMTP活性对它们的辅因子活性进行了生物学相关的分子筛选。结果，发现磷脂，鞘脂和油酸在协助SMTP-7作用方面是活性的。相反，硬脂酸和胆汁酸没有活性。因此，化合物不仅需要表面活化电位，而且还需要某种结构元素才能充当SMTP-7行为的辅助因子。纤溶酶原分子由PAN域，五个kringle域和一个丝氨酸蛋白酶域组成。观察到SMTP-7的辅因子依赖性作用，包括完整的纤溶酶原（Glu-plasminogen），des-PAN纤溶酶原（Lys-plasminogen）和des- [PAN-（kringles 1-4）]等纤溶酶原物种，包括kringle 5。纤溶酶原（mini-plasminogen）。但是，对于最小的纤溶酶原种类des- [PAN-（kringles 1-4）和一半的kringle 5）]纤溶酶原（micro-plasminogen），未观察到SMTP-7效应。因此，kringle 5对于SMTP-7的作用至关重要。

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