Grape extracts inhibit multiple events in the cell biology of cholera intoxication.
Grape extracts inhibit multiple events in the cell biology of cholera intoxication.
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DOI：
10.1371/journal.pone.0073390
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Teter K
中科院分区：
文献类型：
--
作者：
Reddy S;Taylor M;Zhao M;Cherubin P;Geden S;Ray S;Francis D;Teter K
霍乱弧菌产生霍乱毒素（CT），这是一种AB 5蛋白毒素，主要负责霍乱的大量水样腹泻。CT分泌到细胞外环境中，但毒素攻击宿主细胞胞质溶胶内的Gsα靶标。因此，CT必须穿过细胞膜屏障才能发挥作用。该事件仅发生在毒素通过囊泡逆行运输从细胞表面到达内质网（ER）之后。催化A1多肽，然后从其余的毒素解离，并采取未折叠的构象，促进其转移到胞质溶胶的过程中涉及ER相关的降解的质量控制系统。通过改变CT的囊泡转运和/或CTA 1的ER至胞质溶胶易位来阻断生产性中毒。各种植物化合物已被报道抑制CT的致细胞病变活性，因此在这项工作中，我们评估了葡萄提取物的潜在抗CT特性。目前出售的两种葡萄提取物作为营养补充剂抑制CT和大肠杆菌不耐热毒素对培养细胞和肠循环的活性。即使在最初的毒素暴露后一小时加入提取物，CT中毒也被阻断。涉及催化CTA 1亚基和细胞结合CTB五聚体的宿主-毒素相互作用的特定子集受到影响。提取物阻断毒素与细胞表面的结合，防止分离的CTA 1亚基的展开，抑制CTA 1易位到胞质溶胶，并破坏CTA 1的催化活性。因此，葡萄提取物有可能成为预防或治疗霍乱的新疗法。
Vibrio cholerae produces cholera toxin (CT), an AB5 protein toxin that is primarily responsible for the profuse watery diarrhea of cholera. CT is secreted into the extracellular milieu, but the toxin attacks its Gsα target within the cytosol of a host cell. Thus, CT must cross a cellular membrane barrier in order to function. This event only occurs after the toxin travels by retrograde vesicular transport from the cell surface to the endoplasmic reticulum (ER). The catalytic A1 polypeptide then dissociates from the rest of the toxin and assumes an unfolded conformation that facilitates its transfer to the cytosol by a process involving the quality control system of ER-associated degradation. Productive intoxication is blocked by alterations to the vesicular transport of CT and/or the ER-to-cytosol translocation of CTA1. Various plant compounds have been reported to inhibit the cytopathic activity of CT, so in this work we evaluated the potential anti-CT properties of grape extract. Two grape extracts currently sold as nutritional supplements inhibited CT and Escherichia coli heat-labile toxin activity against cultured cells and intestinal loops. CT intoxication was blocked even when the extracts were added an hour after the initial toxin exposure. A specific subset of host-toxin interactions involving both the catalytic CTA1 subunit and the cell-binding CTB pentamer were affected. The extracts blocked toxin binding to the cell surface, prevented unfolding of the isolated CTA1 subunit, inhibited CTA1 translocation to the cytosol, and disrupted the catalytic activity of CTA1. Grape extract could thus potentially serve as a novel therapeutic to prevent or possibly treat cholera.
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DOI：
10.1083/jcb.141.4.905
发表时间：
1998-05-18
期刊：
The Journal of cell biology
影响因子：
--
作者：
Orlandi PA;Fishman PH
通讯作者：
Fishman PH
影响因子：
3.5
作者：
Majoul, I;Ferrari, D;Soling, HD
通讯作者：
Soling, HD
影响因子：
7.1
作者：
Arts, ICW;Hollman, PCH
通讯作者：
Hollman, PCH
影响因子：
7.7
作者：
Dell'Aica, I;Donà, M;Garbisa, S
通讯作者：
Garbisa, S
影响因子：
--
作者：
Brijesh, S.;Daswani, Poonam;Birdi, Tannaz
通讯作者：
Birdi, Tannaz