Metabolic control of T cell activation and death in SLE.
Metabolic control of T cell activation and death in SLE.
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SLE 中 T 细胞激活和死亡的代谢控制。
DOI：
10.1016/j.autrev.2008.07.041
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发表时间：
2009-01
影响因子：
13.6
通讯作者：
Perl, Andras
中科院分区：
文献类型：
--
作者：
Fernandez, David;Perl, Andras
系统性红斑狼疮（SLE）以t细胞异常活化和死亡为特征，这一过程主要依赖于线粒体中活性氧中间体（ROI）和ATP的受控产生。线粒体跨膜电位（Δψm）是ATP合成和细胞死亡的关键检查点。狼疮T细胞表现出Δψm或线粒体超极化（MHP）的持续升高，以及ATP和谷胱甘肽的消耗，这减少了激活诱导的凋亡，反而使T细胞易于坏死，从而刺激SLE的炎症。no诱导的正常T细胞线粒体生物发生加速了快速期，减少了CD3/CD28共刺激时Ca2+内流的平台期，从而模仿狼疮T细胞的Ca2+信号传导谱。用雷帕霉素治疗SLE患者可改善疾病活动性，使CD3/ cd28诱导的Ca2+通量正常化，但不能影响MHP，这表明Ca2+通量的改变是下游的或独立于线粒体功能障碍。了解MHP的分子基础和后果对于控制SLE中的t细胞激活和死亡信号至关重要。狼疮T细胞表现出线粒体功能障碍线粒体超极化（MHP）和ATP耗竭易使狼疮T细胞坏死死亡，这是促炎性的MHP是由谷胱甘肽耗竭和暴露于一氧化氮（NO）引起的，NO诱导的线粒体生物发生再生狼疮T细胞的Ca2+信号，雷帕霉素治疗使Ca2+通量正常化，但不能使MHP正常化，这表明雷帕霉素的哺乳动物靶点在狼疮中作为MHP的传感器和效应体
Systemic lupus erythematosus (SLE) is characterized by abnormal T-cell activation and death, processes which are crucially dependent on the controlled production of reactive oxygen intermediates (ROI) and of ATP in mitochondria. The mitochondrial transmembrane potential (Δψm) has conclusively emerged as a critical checkpoint of ATP synthesis and cell death. Lupus T cells exhibit persistent elevation of Δψm or mitochondrial hyperpolarization (MHP) as well as depletion of ATP and glutathione which decrease activation-induced apoptosis and instead predispose T cells for necrosis, thus stimulating inflammation in SLE. NO-induced mitochondrial biogenesis in normal T cells accelerates the rapid phase and reduces the plateau of Ca2+ influx upon CD3/CD28 co-stimulation, thus mimicking the Ca2+ signaling profile of lupus T cells. Treatment of SLE patients with rapamycin improves disease activity, normalizes CD3/CD28-induced Ca2+ fluxing but fails to affect MHP, suggesting that altered Ca2+ fluxing is downstream or independent of mitochondrial dysfunction. Understanding the molecular basis and consequences of MHP is essential for controlling T-cell activation and death signaling in SLE. Lupus T cells exhibit mitochondrial dysfunction Mitochondrial hyperpolarization (MHP) and ATP depletion predispose lupus T cells to death by necrosis which is pro-inflammatory MHP is caused by depletion of glutathione and exposure to nitric oxide (NO) NO-induced mitochondrial biogenesis regenerates the Ca2+ signaling profile of lupus T cells Rapamycin treatment normalizes Ca2+ fluxing but not MHP, suggesting that the mammalian target of rapamycin, acts as a sensor and effector of MHP in SLE
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影响因子：
4.8
作者：
Banki, K;Hutter, E;Perl, A
通讯作者：
Perl, A
影响因子：
15.3
作者：
Gilkeson, GS;Mudgett, JS;Seldin, MF;Ruiz, P;Alexander, AA;Misukonis, MA;Pisetsky, DS;Weinberg, JB
通讯作者：
Weinberg, JB
DOI：
10.1073/pnas.261560998
发表时间：
2001-12-18
影响因子：
11.1
作者：
Almeida, A;Almeida, J;Moncada, S
通讯作者：
Moncada, S
影响因子：
32.4
作者：
Ibiza, Sales;Victor, Victor M.;Serrador, Juan M.
通讯作者：
Serrador, Juan M.
DOI：
10.1006/clin.1996.0192
发表时间：
1996-12-01
期刊：
CLINICAL IMMUNOLOGY AND IMMUNOPATHOLOGY
影响因子：
--
作者：
Kovacs, B;Vassilopoulos, D;Tsokos, GC
通讯作者：
Tsokos, GC