【medical-news】关于细胞如何自卫的新进展
发布于 2006-09-26 · 浏览 1348 · IP 日本日本
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New understanding of how cells defend themselves
关于细胞如何自卫的新进展
Medical Research News
Published: Thursday, 21-Sep-2006
Biologists at the EPFL (Ecole Polytechnique Federale de Lausanne) have unveiled a new twist in a metabolic pathway that cells use to defend themselves against toxins made by disease-causing bacteria.
EPFL的生物学家揭示了一个关于代谢途径的新观点，细胞能够用用这条途径来防御致病细菌产生的毒素
The discovery of this pathway, published in the September 22 issue of the journal Cell, advances our understanding of how cells mount a survival response when attacked by bacteria and parasites and also gives insight into the more general process of cell membrane biogenesis.
这条途径的发现，推进了我们对当受到细菌和寄生虫侵犯时细胞如何发动生存反应的理解，同时使我们对更普遍的细胞膜生物合成过程有了了解。它被发表在九月二十二号的《细胞》杂志上。
Bacteria and parasites often use special toxins to perforate the membranes of target cells. These pore-forming toxins are a key weapon in the attack arsenal of some common and virulent bacteria, such as Staphylococcus aureus, well-known for its role in hospital-acquired infections, Streptococcus pneumonie, responsible for middle ear infections and pneumonia, and Helicobacter pylori, implicated in ulcers. Pore-forming toxins compose about a quarter of all known protein toxins that increase the infectivity and severity of bacterial diseases.
细菌和寄生虫经常利用特殊的毒素穿孔于靶细胞的细胞膜。这些孔形成毒素是很常见的有毒力的细菌（如金黄色葡萄球菌，它在院内感染中很出名；链球菌，它能引起中耳感染和肺炎；幽门螺旋杆菌，与溃疡有关。）攻击装备中的关键武器。孔形成毒素包括了大约四分之一我们已知的能够增加细菌疾病的致病力和严重行的蛋白毒素。
Once the toxin perforates the host membrane, ions begin to leak out of the cell. Sensing a drop in its potassium concentration, the cell reacts by forming a multi-protein complex known as an inflammasome. Scientists know that inflammasomes act like a sort of roving security force inside the cell, detecting a variety of danger signals such as bacterial RNA or bits of bacterial flagellin. The inflammasomes join together and activate a protein, caspase-1, that in turn triggers an inflammatory response.
一旦毒素穿孔于宿主细胞膜，离子便开始从细胞中泄漏出去。测知它的钾离子浓度的下降，细胞通过形成被称作炎症小体的多蛋白复合体而发生反应。科学家们知道这种炎症小体就好像是细胞内部的巡逻部队，侦查多种危险信号比如细菌RNA或者细菌鞭毛蛋白。这些炎症小体联合起来可以激活半胱天冬酶-1，这种蛋白依次激活炎症的级联反应。
Van der Goot and her colleagues found that in addition to its normal role as a signal for inflammatory response, caspase-1 also triggers the cell's central regulators for membrane synthesis, launching a bout of lipid metabolism. This previously undetected part of the response pathway has important implications for cell survival
Van der Goot及其同事发现除了作为炎性反应的***的一般作用外，半胱天冬酶-1还能触发细胞膜合成的中央调节器，发动一次脂类代谢。这个以前反应通路中未被发现的部分对细胞生存有着重要意义。
The Swiss team studied the pathway by using RNA interference to silence genes involved. Interrupting the pathway at any point, either by silencing the genes responsible for the inflammasome formation or the gene for caspase-1, resulted in increased cell death.
瑞士的研究组利用RNA干扰技术使相关基因沉默来研究这条通路。在任一点阻断这条通路，或者沉默与炎症小体形成相关的基因或者编码半胱天冬酶-1的基因，都能导致细胞死亡数目增加。
"We don't yet know the details of the mechanism by which lipid metabolism leads to cell survival," she says. The lipids are probably used to repair the cell membrane, stopping the potassium leak, which itself can kill the cell, and also protecting the cell from additional toxic substances lurking outside.
我们还不清楚脂质代谢导致细胞存活的具体机制，她说，脂质可能用来修复细胞膜，阻断能致细胞死亡的钾离子泄露，还可能保护细胞免受潜藏在细胞外的其它的毒性物质的损伤。
"This result is important, because it also explains so much in terms of basic cell physiology," notes Van der Goot. If a cell absorbs too much water, for example, this pathway would be triggered. The lipids formed in the metabolic pathway would enable the cell to enlarge its membrane to accommodate the extra water.
这个结果很重要，因为它在基础细胞生理学上能够解释很多现象，Van der Goot说，如果一个细胞吸收了过多的水分，这条通路将会被激活。这条代谢途径形成的脂质能够使细胞膜扩大以容纳额外的水分。
"Toxins have co-evolved with their hosts for a long time," says Van der Goot. "That makes them good tools with which to study normal cell physiology. This study is a case in point - using a toxin, we have the first step in an understanding of how cells can regulate their membranes in order to maintain a particular ion concentration."
毒素已经和宿主共同演化了很长一段时间，Van der Goot说，这将会使他们成为研究正常细胞生理学的良好工具。这项研究正好是个例证—运用毒素，我们在理解细胞如何调节细胞膜以维持特定离子的浓度迈出了第一步。
The research focused on epithelial cells, the cells that line the gut and blood vessels. Van der Goot explains that because they form a protective layer, it's critical for the organism that these cells survive, even if they don't function correctly. If the cell dies, it leaves the underlying tissue exposed. She hypothesizes that the toxin response pathway may be different for other types of cells. Immune cells, for example, may be better off committing suicide if their membranes are penetrated, because they could become deadly if their function is compromised.
研究主要集中在上皮细胞上，即那些分布在肠道和血管壁的细胞。Van der Goot解释说这些细胞的存活对组织非常重要，即便它们不能正确的发挥功能，因为它们形成了一层保护膜。如果细胞死亡，将会使下层的组织暴露。她猜测这个毒性反应通路在别的类型的细胞上是不同的。比如说免疫细胞，如果它们的细胞膜被穿透，自杀是比较有利的，因为他们的功能耐受将会是致命的。
Van der Goot adds that a better understanding of the biochemical pathway that allows epithelial cells to survive an invasion by a pore-forming toxin will prove valuable as biomedical researchers try to develop drugs to fight antibiotic-resistant strains of bacteria that use these toxins as part of their hijacking strategy.
Van der Goot补充道，正当生物医学研究者尝试开发药物治疗那些利用这些毒素作为侵袭手段的耐药菌株时，更清楚地了解这条能够使上皮细胞在穿孔毒素的侵袭下存活的生化通路，将会证明是有价值的
http://www.epfl.ch
关于细胞如何自卫的新进展
Medical Research News
Published: Thursday, 21-Sep-2006
Biologists at the EPFL (Ecole Polytechnique Federale de Lausanne) have unveiled a new twist in a metabolic pathway that cells use to defend themselves against toxins made by disease-causing bacteria.
EPFL的生物学家揭示了一个关于代谢途径的新观点，细胞能够用用这条途径来防御致病细菌产生的毒素
The discovery of this pathway, published in the September 22 issue of the journal Cell, advances our understanding of how cells mount a survival response when attacked by bacteria and parasites and also gives insight into the more general process of cell membrane biogenesis.
这条途径的发现，推进了我们对当受到细菌和寄生虫侵犯时细胞如何发动生存反应的理解，同时使我们对更普遍的细胞膜生物合成过程有了了解。它被发表在九月二十二号的《细胞》杂志上。
Bacteria and parasites often use special toxins to perforate the membranes of target cells. These pore-forming toxins are a key weapon in the attack arsenal of some common and virulent bacteria, such as Staphylococcus aureus, well-known for its role in hospital-acquired infections, Streptococcus pneumonie, responsible for middle ear infections and pneumonia, and Helicobacter pylori, implicated in ulcers. Pore-forming toxins compose about a quarter of all known protein toxins that increase the infectivity and severity of bacterial diseases.
细菌和寄生虫经常利用特殊的毒素穿孔于靶细胞的细胞膜。这些孔形成毒素是很常见的有毒力的细菌（如金黄色葡萄球菌，它在院内感染中很出名；链球菌，它能引起中耳感染和肺炎；幽门螺旋杆菌，与溃疡有关。）攻击装备中的关键武器。孔形成毒素包括了大约四分之一我们已知的能够增加细菌疾病的致病力和严重行的蛋白毒素。
Once the toxin perforates the host membrane, ions begin to leak out of the cell. Sensing a drop in its potassium concentration, the cell reacts by forming a multi-protein complex known as an inflammasome. Scientists know that inflammasomes act like a sort of roving security force inside the cell, detecting a variety of danger signals such as bacterial RNA or bits of bacterial flagellin. The inflammasomes join together and activate a protein, caspase-1, that in turn triggers an inflammatory response.
一旦毒素穿孔于宿主细胞膜，离子便开始从细胞中泄漏出去。测知它的钾离子浓度的下降，细胞通过形成被称作炎症小体的多蛋白复合体而发生反应。科学家们知道这种炎症小体就好像是细胞内部的巡逻部队，侦查多种危险信号比如细菌RNA或者细菌鞭毛蛋白。这些炎症小体联合起来可以激活半胱天冬酶-1，这种蛋白依次激活炎症的级联反应。
Van der Goot and her colleagues found that in addition to its normal role as a signal for inflammatory response, caspase-1 also triggers the cell's central regulators for membrane synthesis, launching a bout of lipid metabolism. This previously undetected part of the response pathway has important implications for cell survival
Van der Goot及其同事发现除了作为炎性反应的***的一般作用外，半胱天冬酶-1还能触发细胞膜合成的中央调节器，发动一次脂类代谢。这个以前反应通路中未被发现的部分对细胞生存有着重要意义。
The Swiss team studied the pathway by using RNA interference to silence genes involved. Interrupting the pathway at any point, either by silencing the genes responsible for the inflammasome formation or the gene for caspase-1, resulted in increased cell death.
瑞士的研究组利用RNA干扰技术使相关基因沉默来研究这条通路。在任一点阻断这条通路，或者沉默与炎症小体形成相关的基因或者编码半胱天冬酶-1的基因，都能导致细胞死亡数目增加。
"We don't yet know the details of the mechanism by which lipid metabolism leads to cell survival," she says. The lipids are probably used to repair the cell membrane, stopping the potassium leak, which itself can kill the cell, and also protecting the cell from additional toxic substances lurking outside.
我们还不清楚脂质代谢导致细胞存活的具体机制，她说，脂质可能用来修复细胞膜，阻断能致细胞死亡的钾离子泄露，还可能保护细胞免受潜藏在细胞外的其它的毒性物质的损伤。
"This result is important, because it also explains so much in terms of basic cell physiology," notes Van der Goot. If a cell absorbs too much water, for example, this pathway would be triggered. The lipids formed in the metabolic pathway would enable the cell to enlarge its membrane to accommodate the extra water.
这个结果很重要，因为它在基础细胞生理学上能够解释很多现象，Van der Goot说，如果一个细胞吸收了过多的水分，这条通路将会被激活。这条代谢途径形成的脂质能够使细胞膜扩大以容纳额外的水分。
"Toxins have co-evolved with their hosts for a long time," says Van der Goot. "That makes them good tools with which to study normal cell physiology. This study is a case in point - using a toxin, we have the first step in an understanding of how cells can regulate their membranes in order to maintain a particular ion concentration."
毒素已经和宿主共同演化了很长一段时间，Van der Goot说，这将会使他们成为研究正常细胞生理学的良好工具。这项研究正好是个例证—运用毒素，我们在理解细胞如何调节细胞膜以维持特定离子的浓度迈出了第一步。
The research focused on epithelial cells, the cells that line the gut and blood vessels. Van der Goot explains that because they form a protective layer, it's critical for the organism that these cells survive, even if they don't function correctly. If the cell dies, it leaves the underlying tissue exposed. She hypothesizes that the toxin response pathway may be different for other types of cells. Immune cells, for example, may be better off committing suicide if their membranes are penetrated, because they could become deadly if their function is compromised.
研究主要集中在上皮细胞上，即那些分布在肠道和血管壁的细胞。Van der Goot解释说这些细胞的存活对组织非常重要，即便它们不能正确的发挥功能，因为它们形成了一层保护膜。如果细胞死亡，将会使下层的组织暴露。她猜测这个毒性反应通路在别的类型的细胞上是不同的。比如说免疫细胞，如果它们的细胞膜被穿透，自杀是比较有利的，因为他们的功能耐受将会是致命的。
Van der Goot adds that a better understanding of the biochemical pathway that allows epithelial cells to survive an invasion by a pore-forming toxin will prove valuable as biomedical researchers try to develop drugs to fight antibiotic-resistant strains of bacteria that use these toxins as part of their hijacking strategy.
Van der Goot补充道，正当生物医学研究者尝试开发药物治疗那些利用这些毒素作为侵袭手段的耐药菌株时，更清楚地了解这条能够使上皮细胞在穿孔毒素的侵袭下存活的生化通路，将会证明是有价值的
http://www.epfl.ch
最后编辑于 2006-09-29 · 浏览 1348
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