Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells overexpressing cytochrome P450 2E1.
Increased oxidative stress and cytotoxicity by hydrogen sulfide in HepG2 cells overexpressing cytochrome P450 2E1.
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DOI：
10.1007/s10565-011-9198-2
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发表时间：
2011-12
影响因子：
6.1
通讯作者：
Tackett, Jonathan
中科院分区：
文献类型：
--
作者：
Caro, Andres A.;Thompson, Sarah;Tackett, Jonathan
这项工作的主要目的是评价硫化氢对HepG 2细胞氧化应激和细胞毒性参数的影响，并评估细胞色素P450 2 E1（CYP 2 E1）活性调节硫化氢对氧化应激和细胞毒性影响的程度。硫氢化钠（NaHS）在非P450表达的HepG 2细胞（C34细胞）和CYP 2 E1过表达的HepG 2细胞（E47细胞）中引起时间和浓度依赖性细胞毒性;然而，在E47中NaHS依赖性细胞毒性高于C34细胞。NaHS在C34和E47细胞中的细胞毒性本质上主要是坏死性的，并且与线粒体膜电位的早期降低相关。NaHS仅在E47细胞中导致亲脂性（C11-BODIPY 581/591）和亲水性（DCFH-DA）探针的氧化增加，在明显细胞毒性之前的时间点。Trolox是一种两亲性抗氧化剂，部分抑制了暴露于NaHS的E47细胞中检测到的细胞毒性和增加的氧化应激。细胞渗透性铁螯合剂和CYP 2 E1抑制剂在NaHS存在下显著抑制E47细胞中C11-BODIPY 581/591的氧化。NaHS在补充有代表性的多不饱和脂肪酸（二十二碳六烯酸）的E47细胞中产生脂质过氧化和细胞毒性，但在C34细胞中不产生脂质过氧化和细胞毒性;这些作用被亲脂性抗氧化剂α-生育酚抑制。这些数据表明，CYP 2 E1通过产生铁依赖性氧化应激和脂质过氧化来增强HepG 2细胞中H2S依赖性细胞毒性。
The main objectives of this work were to evaluate the effects of hydrogen sulfide on oxidative stress and cytotoxicity parameters in HepG2 cells and to assess the extent to which cytochrome P450 2E1 (CYP2E1) activity modulates the effects of hydrogen sulfide on oxidative stress and cytotoxicity. Sodium hydrosulfide (NaHS) caused time- and concentration-dependent cytotoxicity in both non-P450-expressing HepG2 cells (C34 cells) and CYP2E1-overexpressing HepG2 cells (E47 cells); however, NaHS-dependent cytotoxicity was higher in E47 than C34 cells. Cytotoxicity by NaHS in C34 and E47 cells was mainly necrotic in nature and associated with an early decrease in mitochondrial membrane potential. NaHS caused increased oxidation of lipophilic (C11-BODIPY581/591) and hydrophilic (DCFH-DA) probes only in E47 cells, at a time point prior to overt cytotoxicity. Trolox, an amphipathic antioxidant, partially inhibited both the cytotoxicity and the increased oxidative stress detected in E47 cells exposed to NaHS. Cell-permeable iron chelators and CYP2E1 inhibitors significantly inhibited the oxidation of C11-BODIPY581/591 in E47 cells in the presence of NaHS. NaHS produced lipid peroxidation and cytotoxicity in E47 cells supplemented with a representative polyunsaturated fatty acid (docosahexaenoic acid) but not in C34 cells; these effects were inhibited by α-tocopherol, a lipophilic antioxidant. These data suggest that CYP2E1 enhances H2S-dependent cytotoxicity in HepG2 cells through the generation of iron-dependent oxidative stress and lipid peroxidation.
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影响因子：
3.6
作者：
Chen, Q;Cederbaum, AI
通讯作者：
Cederbaum, AI
影响因子：
4.7
作者：
Chang, MC;Ho, YS;Jeng, JH
通讯作者：
Jeng, JH
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2.8
作者：
Attene-Ramos, Matias S.;Nava, Gerardo M.;Gaskins, H. Rex
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Gaskins, H. Rex
影响因子：
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作者：
Kimura, Y;Kimura, H
通讯作者：
Kimura, H
影响因子：
14.8
作者：
Lorenz, Holger;Hailey, Dale W.;Lippincott-Schwartz, Jennifer
通讯作者：
Lippincott-Schwartz, Jennifer