School of Pharmacy, Second Military Medical University, Shanghai, People's Republic of China.
PLoS One. 2011 Jan 5;6(1):e15808. doi: 10.1371/journal.pone.0015808.
Trehalose is a non-reducing disaccharide and can be accumulated in response to heat or oxidative stresses in Candida albicans. Here we showed that a C. albicans tps1Δ mutant, which is deficient in trehalose synthesis, exhibited increased apoptosis rate upon H(2)O(2) treatment together with an increase of intracellular Ca(2+) level and caspase activity. When the intracellular Ca(2+) level was stimulated by adding CaCl(2) or A23187, both the apoptosis rate and caspase activity were increased. In contrast, the presence of two calcium chelators, EGTA and BAPTA, could attenuate these effects. Moreover, we investigated the role of Ca(2+) pathway in C. albicans apoptosis and found that both calcineurin and the calcineurin-dependent transcription factor, Crz1p, mutants showed decreased apoptosis and caspase activity upon H(2)O(2) treatment compared to the wild-type cells. Expression of CaMCA1, the only gene found encoding a C. albicans metacaspase, in calcineurin-deleted or Crz1p-deleted cells restored the cell sensitivity to H(2)O(2). Our results suggest that Ca(2+) and its downstream calcineurin/Crz1p/CaMCA1 pathway are involved in H(2)O(2)-induced C. albicans apoptosis. Inhibition of this pathway might be the mechanism for the protective role of trehalose in C. albicans.
海藻糖是一种非还原性二糖，能够在白色念珠菌响应热或氧化应激时积累。在这里，我们发现一株缺乏海藻糖合成的白色念珠菌 tps1Δ 突变株，在用 H2O2 处理时其细胞凋亡率增加，同时细胞内 Ca2+水平和半胱天冬酶活性升高。当用 CaCl2 或 A23187 刺激细胞内 Ca2+水平时，细胞凋亡率和半胱天冬酶活性均增加。相反，用两种钙螯合剂 EGTA 和 BAPTA 存在时，这些效应可以减弱。此外，我们研究了 Ca2+途径在白色念珠菌凋亡中的作用，发现与野生型细胞相比，钙调神经磷酸酶和钙调神经磷酸酶依赖性转录因子 Crz1p 突变体在用 H2O2 处理时凋亡和半胱天冬酶活性降低。在钙调神经磷酸酶缺失或 Crz1p 缺失细胞中表达 CaMCA1，一种编码白色念珠菌 metacaspase 的唯一基因，恢复了细胞对 H2O2 的敏感性。我们的结果表明，Ca2+及其下游钙调神经磷酸酶/Crz1p/CaMCA1 途径参与了 H2O2 诱导的白色念珠菌凋亡。抑制该途径可能是海藻糖在白色念珠菌中发挥保护作用的机制。
