Hsp90 is involved in apoptosis of Candida albicans by regulating the calcineurin-caspase apoptotic pathway.
Hsp90 is involved in apoptosis of Candida albicans by regulating the calcineurin-caspase apoptotic pathway.
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DOI：
10.1371/journal.pone.0045109
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Jiang Y
中科院分区：
文献类型：
--
作者：
Dai B;Wang Y;Li D;Xu Y;Liang R;Zhao L;Cao Y;Jia J;Jiang Y
白色念珠菌是人类最常见的真菌病原体。最近的证据表明，细胞凋亡的发生在C。白色念珠菌，其可由环境应激如过氧化氢、乙酸和白曲霉素B诱导。C.细胞凋亡受钙调神经磷酸酶-半胱天冬酶途径调节。白念珠菌对棘白菌素的耐药性受Hsp 90的控制。Hsp 90在C.白色仍不清楚。本研究探讨了热休克蛋白90在C.通过使用Hsp 90-受损菌株tetO-Hsp 90/hsp 90对白色念珠菌进行细胞培养，发现在凋亡刺激（包括过氧化氢、乙酸或阿替霉素B处理）下，与Hsp 90/Hsp 90野生型菌株相比，在Hsp 90-受损菌株中发生较少的凋亡，产生较少的ROS，并且更多的细胞存活。此外，Hsp 90受损的细胞在上调caspase编码基因CaMCA 1的表达和激活caspase活性的凋亡刺激后有缺陷。对热休克蛋白90和钙调神经磷酸酶之间关系的研究表明，钙调神经磷酸酶的激活可以上调细胞凋亡，但不能进一步下调细胞凋亡，表明钙调神经磷酸酶是热休克蛋白90的下游。热休克蛋白90抑制剂格尔德霉素（geldanamycin，GdA）可进一步降低钙调神经磷酸酶途径缺陷株的细胞凋亡，表明抑制热休克蛋白90功能比抑制钙调神经磷酸酶功能对细胞凋亡的影响更大。总的来说，这项研究表明，受损的Hsp 90减少了C.白念珠菌，部分通过下调钙调神经磷酸酶-半胱天冬酶途径。
Candida albicans is the most common human fungal pathogen. Recent evidence has revealed the occurrence of apoptosis in C. albicans that is inducible by environmental stresses such as hydrogen peroxide, acetic acid, and amphotericin B. Apoptosis is regulated by the calcineurin-caspase pathway in C. albicans, and calcineurin is under the control of Hsp90 in echinocandin resistance. However, the role of Hsp90 in apoptosis of C. albicans remains unclear. In this study, we investigated the role of Hsp90 in apoptosis of C. albicans by using an Hsp90-compromised strain tetO-HSP90/hsp90 and found that upon apoptotic stimuli, including hydrogen peroxide, acetic acid or amphotericin B treatment, less apoptosis occurred, less ROS was produced, and more cells survived in the Hsp90-compromised strain compared with the Hsp90/Hsp90 wild-type strain. In addition, Hsp90-compromised cells were defective in up-regulating caspase-encoding gene CaMCA1 expression and activating caspase activity upon the apoptotic stimuli. Investigations on the relationship between Hsp90 and calcineurin revealed that activation of calcineurin could up-regulate apoptosis but could not further down-regulate apoptosis in Hsp90-compromised cells, indicating that calcineurin was downstream of Hsp90. Hsp90 inhibitor geldanamycin (GdA) could further decrease the apoptosis in calcineurin-pathway-defect strains, indicating that compromising Hsp90 function had a stronger effect than compromising calcineurin function on apoptosis. Collectively, this study demonstrated that compromised Hsp90 reduced apoptosis in C. albicans, partially through downregulating the calcineurin-caspase pathway.
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影响因子：
6.7
作者：
Robbins N;Uppuluri P;Nett J;Rajendran R;Ramage G;Lopez-Ribot JL;Andes D;Cowen LE
通讯作者：
Cowen LE
影响因子：
64.5
作者：
Chipuk JE;McStay GP;Bharti A;Kuwana T;Clarke CJ;Siskind LJ;Obeid LM;Green DR
通讯作者：
Green DR
缺乏 CaMCA1 编码的元半胱天冬酶的白色念珠菌细胞表现出对氧化应激诱导的死亡和能量代谢变化的抵抗力
影响因子：
3
作者：
Cao, YingYing;Huang, Shan;Jiang, YuanYing
通讯作者：
Jiang, YuanYing
影响因子：
6.7
作者：
LaFayette SL;Collins C;Zaas AK;Schell WA;Betancourt-Quiroz M;Gunatilaka AA;Perfect JR;Cowen LE
通讯作者：
Cowen LE
影响因子：
2.5
作者：
Santos, M;de Larrinoa, IF
通讯作者：
de Larrinoa, IF