| Paraoxonase-1介导硫化氢的抗甲醛神经毒性作用 |
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| 引用本文： | 张平,李祥,任衍开,王春燕,邹伟,唐小卿. Paraoxonase-1介导硫化氢的抗甲醛神经毒性作用[J]. 生物化学与生物物理进展, 2014, 41(5): 487-496 |
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| 作者姓名： | 张平 李祥 任衍开 王春燕 邹伟 唐小卿 |
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| 作者单位： | 南华大学附属南华医院神经病科,南华大学附属第一医院麻醉科,南华大学医学院神经科学研究所,南华大学医学院病理生理学教研室,南华大学附属南华医院神经病科,南华大学医学院神经科学研究所 |
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| 基金项目： | 国家自然科学基金 (81200985，81071005)，湖南省自然科学基金 (11JJ3117)和教育部留学回国人员启动基金 ([2010]508). |
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| 摘 要： | 我们以往的研究工作证实了硫化氢(hydrogen sulfide,H2S)对甲醛神经毒性和氧化应激具有拮抗作用.Paraoxonase-1(PON-1)是机体重要的内源性抗氧化剂.本研究的目的是探讨PON-1是否可介导H2S的抗甲醛神经毒性作用.采用甲醛损伤PC12细胞为甲醛神经毒性的细胞模型.硫氢化钠(NaHS,一种H2S的供体)不仅可以上调PC12细胞PON-1的活力,还可恢复甲醛对PC12细胞PON-1表达与活力的抑制作用.2-hydroxyquinoline(2-HQ)是一种选择性PON-1抑制剂,它可显著降低H2S对甲醛细胞毒性、凋亡和活性氧(reactive oxygen species,ROS)累积的抑制作用.而且,2-HQ可阻止H2S逆转甲醛激活PC12细胞caspase-3和下调PC12细胞bcl-2表达.结果提示H2S依赖PON-1去保护PC12细胞对抗甲醛的神经毒性.我们的这一发现表明PON-1有希望成为防治甲醛神经损伤的新靶点.
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| 关 键 词： | 甲醛 硫化氢 paraoxonase- 凋亡 活性氧 |
| 收稿时间： | 2013-07-21 |
| 修稿时间： | 2013-09-16 |
Paraoxonase-1 Mediates Hydrogen Sulfide-induced Protection Against Formaldehyde Neurotoxicity |
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| ZHANG Ping,LI Xiang,REN Yan-Kai,WANG Chun-Yan,ZOU Wei and TANG Xiao-Qing. Paraoxonase-1 Mediates Hydrogen Sulfide-induced Protection Against Formaldehyde Neurotoxicity[J]. Progress In Biochemistry and Biophysics, 2014, 41(5): 487-496 |
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| Authors: | ZHANG Ping LI Xiang REN Yan-Kai WANG Chun-Yan ZOU Wei TANG Xiao-Qing |
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| Affiliation: | Department of Neurology, Nanhua Affiliated Hospital, University of South China,Department of Anesthesiology, the First Affiliated Hospital, University of South China,Institute of Neuroscience, Medical College, University of south China,Department of pathophysiology, Medical College, University of south China,Department of Neurology, Nanhua Affiliated Hospital, University of South China,Institute of Neuroscience, Medical College, University of south China |
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| Abstract: | We have previously demonstrated the protective function of hydrogen sulfide (H2S) against the neurotoxicity and oxidative stress of formaldehyde (FA). Paraoxonase-1 (PON-1) is a pivotal endogenous antioxidant. The aim of this present study is to investigate whether PON-1 mediates the protection of H2S against FA-induced neurotoxicity. In the present work, PC12 cells treated with FA were established to the model of FA-induced neurotoxicity. Treatment of PC12 cells with NaHS (a donor of H2S) not only upregulates the activity of PON-1,but also significantly restores FA-induced downregulation of PON-1 activity and expression. A selective inhibitor of PON-1, 2-hydroxyquinoline (2-HQ), markedly attenuated H2S-induced neuroprotection against FA-induced cytotoxicity, apoptosis, and accumulation of intracellular reactive oxygen species (ROS) in PC12 cells. Furthermore, 2-HQ blocks H2S to reverse FA-caused activation of caspase-3 and downregulation of bcl-2 expression in PC12 cells. These results indicate that H2S protects PC12 cells against FA-induced neurotoxicity in a PON-1-dependant manner. Our findings suggest a promising role of PON-1 as a novel therapeutic target for neuronal damage after FA exposure. |
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| Keywords: | Formaldehyde Hydrogen sulfide Paraoxonase-1 apoptosis reactive oxygen species |
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