转录因子Cup2对白念珠菌铜离子代谢、氧化应激调控作用的初步研究
投稿时间:2017-02-28  修订日期:2017-05-03  点此下载全文
引用本文:张金宇,王丽红,秦玉璘,张璐璐,姜远英,曹永兵.转录因子Cup2对白念珠菌铜离子代谢、氧化应激调控作用的初步研究[J].药学实践杂志,2017,35(3):224~228
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作者单位E-mail
张金宇 第二军医大学药学院新药研究中心, 上海 200433  
王丽红 中国药科大学, 江苏南京 211198  
秦玉璘 第二军医大学药学院新药研究中心, 上海 200433  
张璐璐 第二军医大学药学院新药研究中心, 上海 200433  
姜远英 第二军医大学药学院新药研究中心, 上海 200433  
曹永兵 第二军医大学药学院新药研究中心, 上海 200433 ybcao@vip.sina.com 
基金项目:国家自然科学基金资助项目(81673478)
中文摘要:目的 利用白念珠菌(Candida albicans)不同转录因子基因缺失菌,考察参与调控铜离子(Cu2+)代谢和氧化应激的重要转录因子。方法 点板实验(spot assay)、生长曲线法。结果 spot assay筛选发现,转录因子Cup2缺失菌Cup2Δ/Δ对Cu2+的敏感性增加,进一步研究表明Cup2Δ/Δ在含5 mmol/L的Cu2+培养液中生长缓慢;Cup2Δ/Δ对H2O2的敏感性也有所增加,而且Cu2+协同H2O2发挥抑菌作用,在BCS螯合Cu2+后,增加了Cup2Δ/Δ和亲本菌SN250对H2O2诱导的氧化应激的耐受性。在氟康唑、咪康唑和酮康唑敏感性实验中,Cup2Δ/Δ并未表现出对唑类药物敏感。结论 敲除转录因子Cup2,可增加白念珠菌对Cu2+和H2O2的敏感性。转录因子Cup2可能参与调控白念珠菌对Cu2+的代谢和H2O2诱导的氧化应激反应,但并未参与对唑类药物耐药性的调控。
中文关键词:白念珠菌  转录因子Cup2  铜离子(Cu2+  过氧化氢  药物敏感性
 
Regulation and control of transcription factor Cup2 on Cu2+ metabolism and oxidative stress in Candida albicans
Abstract:Objective To detect the transcription factors of copper ion (Cu2+) metabolism and oxidative stress by Candida albicans knocked down different transcription factors. Methods Spot assay, growth curve were used. Results The sensitivity to Cu2+ in Cup2Δ/Δ was increasing and the growth of Cup2Δ/Δ was inhibited in 5 mmol /L Cu2+ medium. The results showed that Cup2Δ/Δ also increased the sensitivity to H2O2, interestingly, Cu2+and H2O2 played a synergistic antifungal effect.The tolerance of Cup2Δ/Δ and SN250 to H2O2 induced oxidative stress was increased after BCS chelating Cu2+. In the fluconazole, miconazole and ketoconazole susceptibility experiments, Cup2Δ/Δ did not show susceptibility to azole drugs. Conclusion Knockout transcription factor Cup2, which could increase the sensitivity to Cu2+ and H2O2in Candida albicans. Transcription factor Cup2 might be involved in the regulation and control of Candida albicansmetabolism on Cu2+ and oxidative stress induced by H2O2, but not involved in the regulation and control of drug resistance to azole drugs.
keywords:Candida albicans  transcription factor Cup2  copper ion (Cu2+)  hydrogen peroxide(H2O2)  drug susceptibility
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