Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells.
Cigarette smoke extract upregulates heme oxygenase-1 via PKC/NADPH oxidase/ROS/PDGFR/PI3K/Akt pathway in mouse brain endothelial cells.
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DOI：
10.1186/1742-2094-8-104
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发表时间：
2011-08-24
影响因子：
9.3
通讯作者：
Yang CM
中科院分区：
文献类型：
--
作者：
Shih RH;Cheng SE;Hsiao LD;Kou YR;Yang CM
在大脑中，血红素氧合酶（HO-1）的诱导形式最近已被证明是加剧早期脑损伤所产生的脑出血性中风的发病率已与吸烟有关。有趣的是，香烟烟雾（CS）或CS中存在的化学物质已被证明可诱导HO-1在各种细胞类型中的表达，包括脑内皮细胞。然而，CS调节HO-1蛋白表达的机制在脑血管中并不完全清楚。本研究的目的是探讨CS调节脑内皮细胞HO-1蛋白表达的机制。培养的脑内皮细胞（bEnd.3）用于研究香烟烟雾提取物（PPCSE）的颗粒相是否调节HO-1表达，并研究bEnd.3细胞中HO-1表达所涉及的分子机制。我们证明，PPCSE（30 μg/ml）显着诱导HO-1蛋白表达和其酶活性在bEnd.3细胞中测定的蛋白质印迹和胆红素形成，分别。PPCSE诱导HO-1表达是通过磷脂酰胆碱磷脂酶C（PC-PLC）、PKCδ和PI 3 K/Akt介导的。ROS清除剂N-乙酰-L-半胱氨酸（NAC）可阻断PPCSE诱导的ROS生成和HO-1表达。用PKCδ（rottlerin）和NADPH氧化酶的选择性抑制剂[氯化二苯碘铵（DPI）和夹竹桃素（APO）]预处理可减弱PPCSE诱导的NADPH氧化酶活性、ROS生成和HO-1表达。此外，我们发现PPCSE通过NADPH氧化酶/ROS依赖性PDGFR磷酸化诱导PI 3 K/Akt激活。综上所述，这些结果表明，在bEnd. 3细胞中，PPCSE诱导的HO-1表达是由PC-PLC/PKCδ/NADPH氧化酶依赖性PDGFR/PI 3 K/Akt途径介导的。
In the brain, the inducible form of heme oxygenase (HO-1) has been recently demonstrated to exacerbate early brain injury produced by intracerebral hemorrhagic stroke which incident rate has been correlated with cigarette smoking previously. Interestingly, cigarette smoke (CS) or chemicals present in CS have been shown to induce HO-1 expression in various cell types, including cerebral endothelial cells. However, the mechanisms underlying CS modulating HO-1 protein expression are not completely understood in the brain vessels. The aim of the present study was to investigate the mechanisms underlying CS modulating HO-1 protein expression in cerebral endothelial cells. Cultured cerebral endothelial cells (bEnd.3) were used to investigate whether a particulate phase of cigarette smoke extract (PPCSE) regulates HO-1 expression and to investigate the molecular mechanisms involved in HO-1 expression in bEnd.3 cells. We demonstrated that PPCSE (30 μg/ml) significantly induced HO-1 protein expression and its enzymatic activity in bEnd.3 cells determined by western blotting and bilirubin formation, respectively. PPCSE-induced HO-1 expression was mediated through phosphatidylcholine phospholipase C (PC-PLC), PKCδ, and PI3K/Akt which were observed by pretreatment with their respective pharmacological inhibitors or transfection with dominant negative mutants of PKCδ and Akt. ROS scavenger (N-acetyl-L-cysteine, NAC) blocked the PPCSE-induced ROS generation and HO-1 expression. Pretreatment with selective inhibitors of PKCδ (rottlerin) and NADPH oxidase [diphenyleneiodonium chloride (DPI) and apocynin (APO)] attenuated the PPCSE-induced NADPH oxidase activity, ROS generation, and HO-1 expression. In addition, we found that PPCSE induced PI3K/Akt activation via NADPH oxidase/ROS-dependent PDGFR phosphorylation. Taken together, these results suggested that PPCSE-induced HO-1 expression is mediated by a PC-PLC/PKCδ/NADPH oxidase-dependent PDGFR/PI3K/Akt pathway in bEnd.3 cells.
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影响因子：
8.3
作者：
Fortuno, Ana;Bidegain, Julen;Zalba, Guillermo
通讯作者：
Zalba, Guillermo
影响因子：
7.4
作者：
Knörr-Wittmann, C;Hengstermann, A;Müller, T
通讯作者：
Müller, T
影响因子：
2.9
作者：
Mostaza, Jose M.;Martin-Jadraque, Raquel;Lahoz, Carlos
通讯作者：
Lahoz, Carlos
影响因子：
4.8
作者：
Eguchi, S;Iwasaki, H;Inagami, T
通讯作者：
Inagami, T
影响因子：
4.1
作者：
Favatier, F;Polla, BS
通讯作者：
Polla, BS