Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry.

Interaction of the carbon monoxide-releasing molecule Ru(CO)3Cl(glycinate) (CORM-3) with Salmonella enterica serovar Typhimurium: in situ measurements of carbon monoxide binding by integrating cavity dual-beam spectrophotometry.
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一氧化碳释放分子 Ru(CO)3Cl(甘氨酸) (CORM-3) 与鼠伤寒沙门氏菌的相互作用:通过集成腔双光束分光光度法原位测量一氧化碳结合。

DOI:
10.1099/mic.0.081042-0
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发表时间:
2014
期刊:
Microbiology (Reading, England)
影响因子:
--
通讯作者:
Rana N
Rana N
中科院分区:
--
文献类型:
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作者:
Rana N

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一氧化碳(CO)是一种与血管结合的有毒气体,但在哺乳动物系统中也起着关键的信号传导和细胞保护作用;尽管吸入这种气体有全身输送的问题,但它可以用于治疗。通过CO释放分子(CO- rms)传递到细胞和组织的CO具有CO气体无法模仿的有益和毒性作用;CO-RMs作为新型抗菌剂也是有吸引力的候选者。鼠伤寒沙门菌是一种引起人类肠胃炎的肠道病原体。最近的研究表明血红素加氧酶-1 (HO-1),一种催化血红素降解为胆绿素、游离铁和一氧化碳的蛋白质,参与宿主对沙门氏菌感染的免疫反应。在一些研究中,通过CO- rm给药CO激发了HO-1诱导的许多保护作用,因此我们研究了一种表征良好的水溶性CO- rm Ru(CO)3Cl(甘氨酸)(CORM-3)对沙门氏菌的影响。CORM-3在明显低于报道的对RAW 264.7巨噬细胞产生毒性的浓度时表现出毒性作用。我们在这里通过氧合血红蛋白试验证明,CORM-3在磷酸盐缓冲液、缓冲的最小培养基或非常丰富的培养基中不会自发释放CO。然而,CORM-3在细胞内积累到高水平(如电感耦合等离子体质谱所示),并在细胞内释放CO。在没有预先浓度的沙门氏菌培养中,我们首次证明了灵敏的双光束积分腔吸收分光光度法可以直接实时检测细菌电子传递链中CORM-3结合释放的CO。CO-RMs的毒性作用提示了在抗菌治疗中作为抗生素佐剂的潜在应用。
Carbon monoxide (CO) is a toxic gas that binds to haems, but also plays critical signalling and cytoprotective roles in mammalian systems; despite problems associated with systemic delivery by inhalation of the gas, it may be employed therapeutically. CO delivered to cells and tissues by CO-releasing molecules (CO-RMs) has beneficial and toxic effects not mimicked by CO gas; CO-RMs are also attractive candidates as novel antimicrobial agents.Salmonella entericaserovar Typhimurium is an enteropathogen causing gastroenteritis in humans. Recent studies have implicated haem oxygenase-1 (HO-1), the protein that catalyses the degradation of haem into biliverdin, free iron and CO, in the host immune response toSalmonellainfection. In several studies, CO administration via CO-RMs elicited many of the protective roles of HO-1 induction and so we investigated the effects of a well-characterized water-soluble CO-RM, Ru(CO)3Cl(glycinate) (CORM-3), onSalmonella. CORM-3 exhibits toxic effects at concentrations significantly lower than those reported to cause toxicity to RAW 264.7 macrophages. We demonstrated here, through oxyhaemoglobin assays, that CORM-3 did not release CO spontaneously in phosphate buffer, buffered minimal medium or very rich medium. CORM-3 was, however, accumulated to high levels intracellularly (as shown by inductively coupled plasma MS) and released CO inside cells. Using growingSalmonellacultures without prior concentration, we showed for the first time that sensitive dual-beam integrating cavity absorption spectrophotometry can detect directly the CO released from CORM-3 binding in real-time to haems of the bacterial electron transport chain. The toxic effects of CO-RMs suggested potential applications as adjuvants to antibiotics in antimicrobial therapy.
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