Antioxidant effect of L-carnitine and its short chain esters -: Relevance for the protection from oxidative stress related cardiovascular damage
Antioxidant effect of L-carnitine and its short chain esters -: Relevance for the protection from oxidative stress related cardiovascular damage
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DOI：
10.1016/j.ijcard.2005.02.053
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发表时间：
2006-02-08
影响因子：
3.5
通讯作者：
Pessina, AC
中科院分区：
文献类型：
--
作者：
Calò, LA;Pagnin, E;Pessina, AC
背景资料：氧化应激增加与所有心血管危险因素相关，活性氧似乎是各种心血管疾病中心肌细胞功能障碍的主要介质。肉毒碱已被证明是有效的病理条件下，其特征在于增加氧化应激和抗氧化作用的L-肉毒碱及其衍生物已被描述，但具体机制尚不清楚。我们在培养的人内皮细胞中评价了L-肉毒碱（C），乙酰基-L-肉毒碱（AC）和丙酰-L-肉毒碱（PC）对基因和蛋白质表达的影响用RT-PCR和Western blot方法检测了氧化应激相关蛋白血红素氧合酶-1（HO-1）和内皮型一氧化氮合酶（ecNOS）在H2 O2诱导的氧化应激中的表达。HO-1和ecNOS基因和蛋白表达在肉毒碱孵育后显著增加。与基础条件相比，氧化应激的诱导增加了HO-1基因表达（0.62 +/- 0.02密度单位对0.48 +/- 0.05，p < 0.01），同时降低了ecNOS基因表达（0.75 +/- 0.04对0.40 +/- 0.08，p < 0.001）。这些结果与蛋白质水平的相似结果相一致。C（0.5-1.0-2.0 mM）、AC（0.1-0.2-0.4 mM）和PC（0.05-0.1-0.2 mM）与H2 O2共孵育进一步增加HO-1基因表达，不仅与H2 O2相比正常化，而且与基础ecNOS mRNA相比甚至增加。结论：这是第一次利用分子生物学方法证实肉毒碱对氧化应激相关标志物HO-1和ecNOS的基因和蛋白表达具有直接的刺激作用。由于HO-1和NO被称为抗氧化剂、抗增殖剂和抗炎剂，它们的表达增加将被预期保护免受氧化应激相关的心血管危险因素和心肌损伤，因此将这种作用添加到肉毒碱作用中涉及的多个途径中。(c)2005爱思唯尔爱尔兰有限公司保留所有权利。
Background: Increased oxidative stress is associated with all cardiovascular risk factors and reactive oxygen species appear to be the principal mediators of cardiomyocite dysfunction in various carviovascular diseases. Carnitine has been shown to be effective in pathologic conditions characterized by increased oxidative stress and an antioxidant effect Of L-carnitine and its derivatives has been described but the specific mechanism is unclear.Methods: We evaluated in human endothelial cells in culture the effect Of L-carnitine (C), acetyl-L-camitine (AC) and propionyl-L-carnitine (PC) on gene and protein expression (RT-PCR and Western blot) of oxidative stress related proteins heme oxygenase-1 (HO-1) and of endothelial NO synthase (ecNOS) in absence and presence of oxidative stress induced by H2O2.Results: HO-1 as well as ecNOS gene and protein expression significantly increased upon Carnitines incubation. Induction of oxidative stress increased HO-1 gene expression compared to basal condition (0.62 +/- 0.02 densitometric units vs. 0.48 +/- 0.05, p < 0.01) while decreased ecNOS gene expression (0.75 +/- 0.04 vs. 0.40 +/- 0.08, p < 0.001). These results were paralleled by similar results at protein level. Coincubation of C (0.5-1.0-2.0 mM), AC (0.1-0.2-0.4 mM) and PC (0.05-0.1-0.2 mM) with H2O2 further increased HO-1 gene expression and not only normalized vs. H2O2 but even increased vs. basal ecNOS mRNA. HO-1 and ecNOS gene expression was also paralleled at protein level by coincubation with C, AC and PC of cells exposed to oxidative stress.Conclusion: This is the first report that has utilized a molecular biological approach to demonstrate a direct stimulatory effect of Carnitines on gene and protein expression of the oxidative stress related markers HO-1 and ecNOS. As HO-1 and NO are known as antioxidant, antiproliferative and anti-inflammatory, their increased expression would be expected to protect from oxidative stress related cardiovascular risk factors and myocardial damage, therefore adding this effect to the multiple pathways involved in the effects of carnitines. (c) 2005 Elsevier Ireland Ltd. All rights reserved.