小胶质细胞 BV-2 细胞的炎症反应包括糖酵解转变，并受线粒体葡萄糖调节蛋白 75/ mortalin 调节。
Inflammatory response of microglial BV-2 cells includes a glycolytic shift and is modulated by mitochondrial glucose-regulated protein 75/mortalin.
机构信息
Department of Anesthesia, Stanford University School of Medicine, 300 Pasteur Drive, Grant Building S272, Stanford, CA 94305, United States.
出版信息
FEBS Lett. 2013 Mar 18;587(6):756-62. doi: 10.1016/j.febslet.2013.01.067. Epub 2013 Feb 8.
Abstract
Recent studies suggest a link between mitochondria and proinflammatory cytokine generation. We previously demonstrated that overexpression of mitochondrial chaperone glucose-regulated protein75 (Grp75/mortalin) protects mitochondria. In this study we investigated the modulation of the lipopolisaccharide (LPS)-induced inflammatory response of microglial BV-2 cells by Grp75. We demonstrate that LPS-induced activation promotes significant metabolic changes suppressing mitochondrial function and increasing glycolysis. Overexpression of Grp75 attenuates the LPS-induced oxidative and metabolic responses, and suppresses proinflammatory activation, which depends on both NF-κB activation and lactate. Thus overexpression of Grp75 provides a novel strategy to modulate proinflammatory cytokine production of relevance to inflammation-associated pathologies.
摘要
最近的研究表明线粒体与前炎性细胞因子的产生之间存在联系。我们之前的研究表明，线粒体伴侣葡萄糖调节蛋白 75（Grp75/ mortalin）的过表达可以保护线粒体。在这项研究中，我们研究了 Grp75 对小胶质细胞 BV-2 细胞脂多糖（LPS）诱导的炎症反应的调节作用。我们证明 LPS 诱导的激活促进了显著的代谢变化，抑制了线粒体功能并增加了糖酵解。Grp75 的过表达可减轻 LPS 诱导的氧化和代谢反应，并抑制依赖于 NF-κB 激活和乳酸的促炎激活。因此，Grp75 的过表达为调节与炎症相关病理有关的促炎细胞因子的产生提供了一种新策略。
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