Bacterial fucose-rich polysaccharide stabilizes MAPK-mediated Nrf2/Keap1 signaling by directly scavenging reactive oxygen species during hydrogen peroxide-induced apoptosis of human lung fibroblast cells.
Bacterial fucose-rich polysaccharide stabilizes MAPK-mediated Nrf2/Keap1 signaling by directly scavenging reactive oxygen species during hydrogen peroxide-induced apoptosis of human lung fibroblast cells.
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DOI：
10.1371/journal.pone.0113663
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Bhattacharyya A
中科院分区：
文献类型：
--
作者：
Roy Chowdhury S;Sengupta S;Biswas S;Sinha TK;Sen R;Basak RK;Adhikari B;Bhattacharyya A
持续的自由基攻击扰乱细胞内稳态并使相关信号通路失调，从而促进应激诱导的细胞死亡。尽管不断开发和实施有效的治疗策略，但压力诱导的毒性的治疗仍然存在局限性。本研究的目的是确定细菌岩藻糖多糖对人肺成纤维细胞（WI 38）过氧化氢（H2 O2）诱导的应激的潜在治疗功效，并了解相关的分子机制。在两种不同的发酵过程中，巨大芽孢杆菌RB-05生物合成两种不同的岩藻糖多糖;其中，具有高岩藻糖含量（约42%）的多糖在体外赋予最大的自由基清除效率。采用HPLC、GC-MS和1H/13 C/2D-COSY NMR对纯化的多糖进行结构表征。H2 O2（300 µM）对WI 38细胞的损伤通过诱导细胞内活性氧（ROS）和破坏线粒体膜通透性，随后凋亡显示出抗增殖作用。多糖（250 µg/mL）通过直接清除细胞内ROS而不是激活内源性抗氧化酶来减弱细胞死亡过程。该过程包括半胱天冬酶-9/3/7的抑制、Bax/Bcl 2比率的降低、易位的Bax和细胞色素c的再定位、Bcl 2家族的抗凋亡成员的上调和MAPK（促分裂原活化蛋白激酶）磷酸化的降低。此外，通过MAPK介导的Nrf 2/Keap 1信号转导和下游细胞保护基因的转录的稳定，细胞内稳态被重新建立。这项分子研究独特地引入了一种富含岩藻糖的细菌多糖作为H2 O2诱导的应激和毒性的潜在抑制剂。
Continuous free radical assault upsets cellular homeostasis and dysregulates associated signaling pathways to promote stress-induced cell death. In spite of the continuous development and implementation of effective therapeutic strategies, limitations in treatments for stress-induced toxicities remain. The purpose of the present study was to determine the potential therapeutic efficacy of bacterial fucose polysaccharides against hydrogen peroxide (H2O2)-induced stress in human lung fibroblast (WI38) cells and to understand the associated molecular mechanisms. In two different fermentation processes, Bacillus megaterium RB-05 biosynthesized two non-identical fucose polysaccharides; of these, the polysaccharide having a high-fucose content (∼42%) conferred the maximum free radical scavenging efficiency in vitro. Structural characterizations of the purified polysaccharides were performed using HPLC, GC-MS, and 1H/13C/2D-COSY NMR. H2O2 (300 µM) insult to WI38 cells showed anti-proliferative effects by inducing intracellular reactive oxygen species (ROS) and by disrupting mitochondrial membrane permeability, followed by apoptosis. The polysaccharide (250 µg/mL) attenuated the cell death process by directly scavenging intracellular ROS rather than activating endogenous antioxidant enzymes. This process encompasses inhibition of caspase-9/3/7, a decrease in the ratio of Bax/Bcl2, relocalization of translocated Bax and cytochrome c, upregulation of anti-apoptotic members of the Bcl2 family and a decrease in the phosphorylation of MAPKs (mitogen activated protein kinases). Furthermore, cellular homeostasis was re-established via stabilization of MAPK-mediated Nrf2/Keap1 signaling and transcription of downstream cytoprotective genes. This molecular study uniquely introduces a fucose-rich bacterial polysaccharide as a potential inhibitor of H2O2-induced stress and toxicities.
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影响因子：
11.4
作者：
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通讯作者：
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影响因子：
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影响因子：
16.6
作者：
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通讯作者：
SVENSSON, S
影响因子：
4.2
作者：
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通讯作者：
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