Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.
Urease from Helicobacter pylori is inactivated by sulforaphane and other isothiocyanates.
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DOI：
10.1016/j.bbrc.2013.03.126
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发表时间：
2013-05-24
影响因子：
3.1
通讯作者：
Talalay P
中科院分区：
文献类型：
--
作者：
Fahey JW;Stephenson KK;Wade KL;Talalay P
幽门螺杆菌感染是非常常见的，导致胃十二指肠炎症，包括消化性溃疡，并增加胃肿瘤的风险。异硫氰酸酯（ITC）萝卜硫素[SF; 1-异硫氰酸基-4-（甲基亚磺酰基）丁烷]来自可食用十字花科植物，如花椰菜是有效的杀菌对螺杆菌，包括耐药菌株，这表明可能的饮食疗法。胃H。幽门螺杆菌感染表现出高的尿素酶活性，其产生氨，中和胃酸，并促进炎症。SF抑制（灭活）尿素酶（刀豆和螺杆菌）的发现提出了这些特性是否可能在功能上相关的问题。脲酶活性的失活速率依赖于酶和SF浓度，并显示一级动力学。用SF处理导致部分纯化的螺杆菌尿素酶在280-340 nm区域的紫外吸收的时间依赖性增加。这为SF的ITC基团与脲酶的半胱氨酸硫醇之间形成二硫代氨基甲酸酯提供了直接的光谱证据。结构上与SF相关的异硫氰酸酯灭活螺杆菌尿素酶的效力是令人惊讶的可变的。与SF密切相关的天然异硫氰酸酯，以前被证明是杀菌的（berteroin，hirsutin，苯乙基异硫氰酸酯，alyssin和erucin），没有抑制尿素酶活性。此外，SF对尿素酶阳性和阴性H. pylori菌株。相反，一些异硫氰酸酯如苯甲酰基-ITC是非常有效的脲酶灭活剂，但不是杀菌剂。因此，SF和其他ITC对螺杆菌的杀菌作用与尿素酶失活无关，但可能减少螺杆菌感染的炎症成分。
Infections by Helicobacter pylori are very common, causing gastroduodenal inflammation including peptic ulcers, and increasing the risk of gastric neoplasia. The isothiocyanate (ITC) sulforaphane [SF; 1-isothiocyanato-4-(methylsulfinyl)butane] derived from edible crucifers such as broccoli is potently bactericidal against Helicobacter, including antibiotic-resistant strains, suggesting a possible dietary therapy. Gastric H. pylori infections express high urease activity which generates ammonia, neutralizes gastric acidity, and promotes inflammation. The finding that SF inhibits (inactivates) urease (jack bean and Helicobacter) raised the issue of whether these properties might be functionally related. The rates of inactivation of urease activity depend on enzyme and SF concentrations and show first order kinetics. Treatment with SF results in time-dependent increases in the ultraviolet absorption of partially purified Helicobacter urease in the 280–340 nm region. This provides direct spectroscopic evidence for the formation of dithiocarbamates between the ITC group of SF and cysteine thiols of urease. The potencies of inactivation of Helicobacter urease by isothiocyanates structurally related to SF were surprisingly variable. Natural isothiocyanates closely related to SF, previously shown to be bactericidal (berteroin, hirsutin, phenethyl isothiocyanate, alyssin, and erucin), did not inactivate urease activity. Furthermore, SF is bactericidal against both urease positive and negative H. pylori strains. In contrast, some isothiocyanates such as benzoyl-ITC, are very potent urease inactivators, but are not bactericidal. The bactericidal effects of SF and other ITC against Helicobacter are therefore not obligatorily linked to urease inactivation, but may reduce the inflammatory component of Helicobacter infections.