The Effects of Palmitic Acid on Nitric Oxide Production by Rat Skeletal Muscle: Mechanism via Superoxide and iNOS Activation
The Effects of Palmitic Acid on Nitric Oxide Production by Rat Skeletal Muscle: Mechanism via Superoxide and iNOS Activation
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DOI：
10.1159/000343307
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发表时间：
2012-01-01
影响因子：
--
通讯作者：
Pithon-Curi, Tania Cristina
中科院分区：
文献类型：
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作者：
Lambertucci, Rafael Herling;Leandro, Carol Gals;Pithon-Curi, Tania Cristina
背景：血浆游离脂肪酸（FFA）浓度升高可导致骨骼肌胰岛素抵抗，对线粒体功能的影响受损，包括氧化磷酸化的解偶联和内源性抗氧化防御的降低。一氧化氮（NO）是一种高度扩散的气体，半衰期为5-10秒，参与多种生理和病理条件。研究了棕榈酸对大鼠骨骼肌细胞产生一氧化氮（NO）的影响及其可能机制。方法：用棕榈酸处理原代培养的大鼠骨骼肌细胞，采用亚硝酸盐测定法（Griess法）和4,5-二氨基荧光素测定法（DAF-2-DA）测定NO的生成。电泳迁移位移法检测核因子κ B （nf - κ B）活化，western blotting检测iNOS蛋白含量。结果：棕榈酸处理增加了一氧化氮的生成。用NOS抑制剂、l -硝基精氨酸（LNA）和l -硝基精氨酸甲基埃斯特（L-NAME）治疗可消除这种作用。棕榈酸处理提高了NF-kappa B活性和iNOS含量。通过在存在或不存在棕榈酸、超氧化物生成系统（X-XO）、NOS抑制剂和SOD-PEG（与聚乙二醇相连的超氧化物歧化酶）的混合物中与DAF-2-DA孵育细胞，研究了超氧化物对一氧化氮生成的参与。棕榈酸和X-XO系统增加了NO的产生，当细胞用NOS抑制剂和SOD-PEG处理时，这种作用被消除。结论：综上所述，棕榈酸通过产生超氧化物、激活核因子κ B和增加iNOS蛋白含量来刺激培养骨骼肌细胞NO的产生。巴塞尔S. Karger股份有限公司版权所有
Background: Increased plasma concentrations of free fatty acids (FFA) can lead to insulin resistance in skeletal muscle, impaired effects on mitochondrial function, including uncoupling of oxidative phosphorylation and decrease of endogenous antioxidant defenses. Nitric oxide (NO) is a highly diffusible gas that presents a half-life of 5-10 seconds and is involved in several physiological and pathological conditions. The effects of palmitic acid on nitric oxide (NO) production by rat skeletal muscle cells and the possible mechanism involved were investigated. Methods: Primary cultured rat skeletal muscle cells were treated with palmitic acid and NO production was assessed by nitrite measurement (Griess method) and 4,5-diaminofluorescein diacetate (DAF-2-DA) assay. Nuclear factor-kappa B (NF-kappa B) activation was evaluated by electrophoretic mobility shift assay and iNOS protein content by western blotting. Results: Palmitic acid treatment increased nitric oxide production. This effect was abolished by treatment with NOS inhibitors, L-nitro-arginine (LNA) and L-nitro-arginine methyl esther (L-NAME). NF-kappa B activation and iNOS content were increased due to palmitic acid treatment. The participation of superoxide on nitric oxide production was investigated by incubating the cells with DAF-2-DA in the presence or absence of palmitic acid, a superoxide generator system (X-XO), a mixture of NOS inhibitors and SOD-PEG (superoxide dismutase linked to polyethylene glycol). Palmitic acid and X-XO system increased NO production and this effect was abolished when cells were treated with NOS inhibitors and also with SOD-PEG. Conclusions: In summary, palmitic acid stimulates NO production in cultured skeletal muscle cells through production of superoxide, nuclear factor-kappa B activation and increase of iNOS protein content. Copyright (C) 2012 S. Karger AG, Basel