Investigation on the induction mechanism of hepatocyte death by fungal reactive oxygen species

真菌活性氧诱导肝细胞死亡的机制研究

• 批准号: 21K15431
• 负责人: Chen Xinyue
• 金额: $ 2.91万
• 依托单位: Tokyo Institute of Technology
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2024-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K15431/
• 关键词: Candida species; ROS production; NOX genes; Drug resistance; Pathogenic Candida; hepatic cell; reactive oxygen species

Candida albicans CaCFL11 showed enhanced expression under the co-culture with hepatic cells, resulting in ROS production and cause hepatocytes apoptosis phenomenon. We constructed heterozygous mutants of CaCFL11 gene promoter fused to GFP. The results from these mutants indicated CaCFL11 expression was regulated in response to co-culture with hepatocytes and helped to target the binding region of transcription factors involved in the CaCFL11 expression. On the other hand, the natural product curcumin has been widely studied as a drug candidate and exhibited antifungal activity against C. albicans. Our study on antifungal drug resistance showed curcumin affected the function of heat shock protein 90 (Hsp90) and drug efflux pump activity of multidrug transporter protein Cdr1 in C. albicans.

白念珠菌CaCFL11在与肝细胞共培养下表达增强，导致ROS产生并引起肝细胞凋亡现象。我们构建了CaCFL 11基因启动子与GFP融合的杂合突变体。这些突变体的结果表明，CaCFL 11的表达在与肝细胞共培养时受到调节，并有助于靶向参与CaCFL 11表达的转录因子的结合区域。另一方面，天然产物姜黄素已被广泛研究作为一种药物候选人，并表现出抗真菌活性对C。白色念珠菌本实验室抗真菌药物耐药性研究表明，姜黄素影响了热休克蛋白90（Hsp90）的功能和多药转运蛋白Cdr 1的药物外排泵活性。白色念珠菌

项目成果

Analysis of hepatocyte apoptosis induction mechanism by pathogenic fungus Candida species

病原真菌念珠菌诱导肝细胞凋亡机制分析

• 发表时间: 2022
• 作者: Maoyi Lin;Maho Shirai;Xinyue Chen;Kanami Orihara;Susumu Kajiwara
• 通讯作者: Susumu Kajiwara