Mechanisms of hydroxyl free radical-induced cellular injury and calcium overloading in alveolar macrophages.
Mechanisms of hydroxyl free radical-induced cellular injury and calcium overloading in alveolar macrophages.
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羟自由基诱导的肺泡巨噬细胞细胞损伤和钙超载的机制。
DOI：
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发表时间：
1993
影响因子：
6.4
通讯作者：
Joseph K. H. Ma
中科院分区：
文献类型：
--
作者：
Yongyut Rojanasakul;Liying Wang;Andre H. Hoffman;Xianglin Shi;Nar S. Dalal;Daniel E. Banks;Joseph K. H. Ma
肺泡巨噬细胞过量产生活性氧自由基被认为在氧化性肺损伤中发挥重要作用。氧自由基形成的主要产物是通过生物芬顿反应产生的高反应性羟基自由基 (.OH)。除了已知的诱导脂质过氧化的能力外，最近的研究表明.OH 可能通过改变 [Ca2+]i 稳态来发挥其细胞毒性作用。为了测试这一潜在机制并研究 .OH 和 Ca2+ 超载在细胞毒性损伤中的关系，将分离的大鼠肺泡巨噬细胞暴露于外部产生的自由基系统 H2O2 (0.01 至 1 mM) 和 Fe2+ (1 mM)，并借助特定的 Ca2+ 指示剂 Fura-2 和膜完整性指示剂碘化丙啶，使用定量荧光显微镜监测它们的 [Ca2+]i 水平和细胞损伤。使用自旋陷阱 5,5-二甲基-1-吡咯啉-N-氧化物 (DMPO) 进行的电子自旋共振测量证实了该系统产生了 .OH 自由基。添加自由基后，巨噬细胞的 [Ca2+]i 表现出快速的初始升高，随后是较慢但更明显的 [Ca2+]i 升高，达到比基础水平高 3 至 5 倍的水平。这一过程先于细胞死亡，核碘化丙啶荧光可以证明这一点。细胞外 Ca2+ 的消耗抑制了 [Ca2+]i 反应和细胞损伤。将细胞与 Ca2+ 通道阻滞剂维拉帕米或 .OH 自由基清除剂甘露醇一起预孵育同样可以抑制 [Ca2+]i 的升高和活力的丧失。细胞 ATP 含量的萤火虫荧光素酶测定表明，.OH 处理后 [Ca2+]i 的变化先于 ATP 的消耗。（摘要截断为 250 字）
Excessive production of reactive oxygen radicals by alveolar macrophages is proposed to play an important role in oxidative lung injury. A major product oxygen radical formation is the highly reactive hydroxyl radical (.OH) generated via a biologic Fenton reaction. In addition to its known ability to induce lipid peroxidation, recent studies have suggested that the .OH may exert its cytotoxic effect through the alteration of [Ca2+]i homeostasis. To test this potential mechanism as well as to investigate the relationship between .OH and Ca2+ overloading in cytotoxic injury, isolated rat alveolar macrophages were exposed to externally generated radical system, H2O2 (0.01 to 1 mM) and Fe2+ (1 mM) and their [Ca2+]i levels and cell injury were monitored using quantitative fluorescence microscopy with the aid of the specific Ca2+ indicator, Fura-2, and membrane integrity indicator, propidium iodide. Electron spin resonance measurements using the spin trap 5,5-dimethyl-1-pyrroline-N-oxide (DMPO) confirmed the production of the .OH radical by this system. Upon the addition of the radicals, the macrophages displayed a rapid initial rise in [Ca2+]i which was followed by a slower but more pronounced [Ca2+]i elevation that reached a level 3 to 5 times higher than the basal level. This process preceded cell death as evident by nuclear propidium iodide fluorescence. Depletion of extracellular Ca2+ inhibited both the [Ca2+]i response and cell injury. Preincubation of the cells with the Ca2+ channel blocker verapamil or .OH radical scavenger mannitol similarly inhibited the [Ca2+]i rise and loss of viability. Firefly luciferase assay of cellular ATP content demonstrated that the alterations in [Ca2+]i following .OH treatment preceded the depletion of ATP.(ABSTRACT TRUNCATED AT 250 WORDS)
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DOI：
10.1016/s0021-9258(17)39218-9
发表时间：
1985-08
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
P. E. Starke;J. Farber
通讯作者：
P. E. Starke;J. Farber
谷胱甘肽还原过程的调节。
影响因子：
5.8
作者：
Reed,DJ
通讯作者：
Reed,DJ
影响因子：
3.9
作者：
MASAKI, N;KYLE, ME;FARBER, JL
通讯作者：
FARBER, JL
氢过氧化物诱导的肺泡巨噬细胞功能和膜完整性损伤：细胞内游离 Ca2 和膜电位的改变。
影响因子：
3.9
作者：
Forman,HJ;Dorio,RJ;Skelton,DC
通讯作者：
Skelton,DC
高氧改变钙对大鼠肺泡巨噬细胞超氧化物产生的影响。
DOI：
10.1152/jappl.1986.60.4.1300
发表时间：
1986
期刊：
Journal of applied physiology (Bethesda, Md. : 1985)
影响因子：
--
作者：
Forman,HJ;Nelson,J;Harrison,G
通讯作者：
Harrison,G