Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells.
Synergistic effect of beta-amyloid protein and interferon gamma on nitric oxide production by C2C12 muscle cells.
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β-淀粉样蛋白和干扰素 γ 对 C2C12 肌细胞产生一氧化氮的协同作用。
DOI：
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发表时间：
2000
期刊：
影响因子：
--
通讯作者：
G. Scarlato
中科院分区：
文献类型：
--
作者：
P. Baron;D. Galimberti;L. Meda;E. Prat;E. Scarpini;G. Conti;M. Moggio;A. Prelle;G. Scarlato
一氧化氮（NO）是多种生理和病理反应的重要介质。NO诱导的氧化应激被认为是包涵体肌炎（inclusion-body myositis，IBM）肌肉组织损伤的发病机制，其特征是β-淀粉样蛋白（beta-amyloid protein，Abeta）在空泡化的肌纤维中沉积。为了确定Abeta是否可以诱导骨骼肌中NO的产生，我们在存在或不存在干扰素γ（IFN-γ）的情况下，用Abeta [1 - 42]或Abeta [25 - 35]肽体外刺激C2C12小鼠骨骼肌细胞。当单独给药时，Abeta肽和IFN-γ都不能刺激C2C12细胞产生亚硝酸盐（NO（2）（-））。然而，IFN-γ与Abeta [1 - 42]或Abeta [25 - 35]的组合导致显著的NO（2）㈠释放到无细胞上清液中。从Abeta/IFN-γ刺激的C2C12细胞获得的RNA的北方印迹分析显示诱导型一氧化氮合酶（iNOS）的mRNA积累增加。此外，约4%的肌肉细胞与Abeta肽和IFN-γ孵育显示DNA片段的超微结构特征。这些发现共同表明，Abeta与IFN-γ的结合通过诱导骨骼肌细胞中iNOS基因表达刺激NO（2）（-）产生，偶尔有核变化的证据表明细胞凋亡形态。这些数据进一步支持Abeta沉积在IBM中假定的氧化损伤发病机制中的作用。
Nitric oxide (NO) is an important mediator of diverse physiological and pathological responses. NO-induced oxidative stress has been proposed in the pathogenesis of muscle tissue damage in inclusion-body myositis (IBM), which is characterized by deposition of beta-amyloid protein (Abeta) in vacuolated muscle fibres. To determine whether Abeta can induce NO production in skeletal muscle, we stimulated C2C12 mouse skeletal muscle cells in vitro with Abeta[1-42] or Abeta[25-35] peptides in the presence or absence of interferon gamma (IFN-gamma). Neither Abeta peptides nor IFN-gamma were able to stimulate nitrite (NO(2)(-)) production by C2C12 cells when given alone. However, combination of IFN-gamma with either Abeta[1-42] or Abeta[25-35] resulted in significant NO(2)(-) release into cell-free supernatants. Northern blot analysis of RNA obtained from Abeta/IFN-gamma-stimulated C2C12 cells revealed increased mRNA accumulation of inducible nitric oxide synthase (iNOS). Moreover, approximately 4% of muscle cells incubated with Abeta peptides and IFN-gamma showed ultrastructural features of DNA fragmentation. These findings, taken together, indicate that the association of Abeta with IFN-gamma stimulates NO(2)(-) production via induction of iNOS gene expression in skeletal muscle cells, with occasional evidence for nuclear changes suggesting apoptotic morphology. These data further support a role for Abeta deposition in the pathogenesis of postulated oxidative damage in IBM.
DOI：
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发表时间：
1992-07
期刊：
The American journal of pathology
影响因子：
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作者：
V. Askanas;W. Engel;R. B. Alvarez
通讯作者：
V. Askanas;W. Engel;R. B. Alvarez
DOI：
10.1016/s0021-9258(17)36703-0
发表时间：
1994-05
期刊：
The Journal of biological chemistry
影响因子：
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作者：
C. Nathan;Q. Xie
通讯作者：
C. Nathan;Q. Xie
DOI：
10.1073/pnas.88.17.7773
发表时间：
1991-09-01
影响因子：
11.1
作者：
STUEHR, DJ;CHO, HJ;NATHAN, CF
通讯作者：
NATHAN, CF