Serofendic acid, a novel substance extracted from fetal calf serum, protects against oxidative stress in neonatal rat cardiac myocytes
Serofendic acid, a novel substance extracted from fetal calf serum, protects against oxidative stress in neonatal rat cardiac myocytes
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DOI：
10.1016/j.jacc.2005.12.055
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发表时间：
2006-05-02
影响因子：
24
通讯作者：
Kita, T
中科院分区：
文献类型：
--
作者：
Takeda, T;Akao, M;Kita, T
目的 我们检查了血清芬地酸 (SFA) 是否对心肌细胞的氧化应激具有保护作用。背景我们之前从胎牛血清的亲脂性提取物中鉴定出一种新型内源性物质 SFA。血清芬地酸保护培养的神经元免受谷氨酸、一氧化氮和氧化应激的细胞毒性。方法将新生大鼠心肌细胞的原代培养物暴露于氧化应激（H2O2，100μmol/l）以诱导细胞死亡。用多种细胞死亡标志物评估了SFA的作用。结果通过末端脱氧核苷酸转移酶介导的dUTP缺口末端标记染色和细胞活力测定来评估，用SFA（100μmol/l）预处理显着抑制了细胞死亡标志物。线粒体膜电位（Delta Psi(m)）的丧失是死亡途径的关键步骤，由基质钙超载和活性氧引发。血清芬迪酸以浓度依赖性方式（饱和度为 100 μmol/l）阻止 H2O2 引起的 Delta Psi(m) 损失。血清芬地酸显着抑制 H2O2 诱导的基质钙超载和细胞内活性氧的积累。 SFA 的保护作用与线粒体三磷酸腺苷敏感钾 (mitoK(ATP)) 通道开放剂二氮嗪相当。此外，mitoK(ATP)通道阻断剂5-羟基癸酸(500μmol/l)消除了SFA的保护作用。 SFA(100μmol/l)和二氮嗪(100μmol/l)并用没有表现出相加作用。因此，SFA 可能通过激活 mitoK(ATP) 通道来抑制氧化剂诱导的线粒体死亡途径。 结论 血清芬地酸通过保护线粒体的功能完整性，保护心肌细胞免受氧化剂诱导的细胞死亡。
OBJECTIVES We examined whether serofendic acid (SFA) has protective effects against oxidative stress in cardiac myocytes.BACKGROUND We previously identified a novel endogenous Substance, SFA, from a lipophilic extract of fetal calf scrum. Serofendic acid protects cultured neurons against the cytotoxicity of glutamate, nitric oxide, and oxidative stress.METHODS Primary cultures of neonatal rat cardiac myocytes were exposed to oxidative stress (H2O2, 100 mu mol/l) to induce cell death. Effects of SFA were evaluated with a number of markers of cell death.RESULTS Pretreatment with SFA (100 mu mol/l) significantly suppressed markers of cell death, as assessed by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeting staining and cell viability assay. Loss of mitochondrial membrane potential (Delta Psi(m)) is a critical step of the death pathway, which is triggered by matrix calcium overload and reactive oxygen species. Serofendic acid prevented the Delta Psi(m) loss induced by H2O2 in a concentration-dependent manner (with saturation by 100 mu mol/l). Serofendic acid remarkably suppressed the H2O2-induccd matrix calciurn overload and intracellular accumulation of reactive oxygen species. The protective effect of SFA was comparable to that of a mitochondrial adenosine triphosphate-sensitive potassium (mitoK(ATP)) channel opener, diazoxide. Furthermore, mitoK(ATP) channel blocker, 5-hydroxydecanoate (500 mu mol/l), abolished the protective effect of SFA. Co-application of SFA (100 mu mol/l) and diazoxide (100 mu mol/l) did not show an additive effect. Thus, SFA inhibited the oxidant-induced mitochondrial death pathway, presumably through activation of the mitoK(ATP) channel.CONCLUSIONS Serofendic acid protects cardiac myocytes against oxidant-induced cell death by preserving the functional integrity of mitochondria.