A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation.
A peptide derived from the highly conserved protein GAPDH is involved in tissue protection by different antifungal strategies and epithelial immunomodulation.
复制标题
源自高度保守的蛋白质GAPDH的肽通过不同的抗真菌策略和上皮免疫调节参与组织保护。
DOI：
10.1038/jid.2012.254
复制
发表时间：
2013-01
影响因子：
6.5
通讯作者：
Schaller, Martin
中科院分区：
文献类型：
--
作者：
Wagener, Jeanette;Schneider, Josef J.;Baxmann, Susann;Kalbacher, Hubert;Borelli, Claudia;Nuding, Sabine;Kuechler, Robert;Wehkamp, Jan;Kaeser, Matthias D.;Maiaelander-Sanchez, Daniela;Braunsdorf, Christina;Hube, Bernhard;Schild, Lydia;Forssmann, Wolf-Georg;Korting, Hans-Christian;Liepke, Cornelia;Schaller, Martin
3-磷酸甘油醛脱氢酶 (GAPDH) 在糖酵解中发挥着重要作用，而且在非代谢过程中也发挥着重要作用，包括转录激活和细胞凋亡。我们报告从人胎盘组织中分离出具有抗菌活性的 hGAPDH (2-32) 片段肽。该肽被致病性酵母白色念珠菌的细胞内化，并启动快速细胞凋亡机制，从而杀死真菌。杀灭作用呈剂量依赖性，10 µg/ml (3.1 µM) 和 100 µg/ml hGAPDH (2-32) 分别可使群体中 45% 和 90% 的真菌细胞去极化。实验性白色念珠菌感染诱导上皮 hGAPDH (2-32) 表达。与未经处理的实验感染相比，添加肽显着减少了组织损伤。较高浓度的片段可抑制白色念珠菌的分泌性天冬氨酸蛋白酶 (Sap) 活性，Sap1p 的 ED50 为 160 mg/l (50 μM)，Sap2p 的 ED50 为 200 mg/l (63 μM)，而 Sap3 根本不被抑制。有趣的是，hGAPDH (2-32) 可诱导显着的上皮 IL-8 和 GM-CSF 分泌，并在低浓度下刺激 TLR4 表达，与白色念珠菌的存在无关，而没有任何毒性粘膜效应。未来，不同抗真菌策略的组合，例如具有免疫调节作用和抑制真菌毒力因子的传统杀真菌剂可能是一种有前途的治疗选择。
Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) plays an important role in glycolysis but also in non-metabolic processes, including transcription activation and apoptosis. We report the isolation of an hGAPDH (2-32) fragment peptide from human placental tissue exhibiting antimicrobial activity. The peptide was internalized by cells of the pathogenic yeast Candida albicans and initiated a rapid apoptotic mechanism, leading to killing of the fungus. Killing was dose-dependent, with 10 µg/ml (3.1 µM) and 100 µg/ml hGAPDH (2-32) depolarizing 45% and 90% of the fungal cells in a population, respectively. Experimental C. albicans infection induced epithelial hGAPDH (2-32) expression. Addition of the peptide significantly reduced the tissue damage as compared to untreated experimental infection. Secreted aspartic proteinases (Saps) activity of C. albicans was inhibited by the fragment at higher concentrations with an ED50 of 160 mg/l (50 μM) for Sap1p and 200 mg/l (63 μM) for Sap2p while Sap3 was not inhibited at all. Interestingly, hGAPDH (2-32) induced significant epithelial IL-8 and GM-CSF secretion and stimulated TLR4 expression at low concentrations independently of the presence of C. albicans without any toxic mucosal effects. In the future, the combination of different antifungal strategies, e.g. a conventional fungicidal with immunomodulatory effects and the inhibition of fungal virulence factors might be a promising treatment option.
登录
查看更多内容
影响因子：
3.4
作者：
Zhu W;Filler SG
通讯作者：
Filler SG
影响因子：
15.9
作者：
Weindl, Guenther;Naglik, Julian R.;Schaller, Martin
通讯作者：
Schaller, Martin
DOI：
10.1016/s1570-0232(03)00245-9
发表时间：
2003-07-05
影响因子：
3
作者：
Liepke, C;Baxmann, S;Forssmann, WG
通讯作者：
Forssmann, WG
影响因子：
64.8
作者：
Schroeder, Bjoern O.;Wu, Zhihong;Wehkamp, Jan
通讯作者：
Wehkamp, Jan
DOI：
10.1016/j.bbagen.2005.07.013
发表时间：
2005-11-30
影响因子：
3
作者：
Yamaji, R;Chatani, E;Nakano, Y
通讯作者：
Nakano, Y