Paraoxonase-1介导硫化氢的抗甲醛神经毒性作用(英文)  

Paraoxonase-1 Mediates Hydrogen Sulfide-induced Protection Against Formaldehyde Neurotoxicity

作　　者：张平[1,1] 李祥[2] 任衍开 王春燕[4] 邹伟[1] 唐小卿[3] 

机构地区：[1]南华大学附属南华医院神经病科,衡阳421001 [2]南华大学附属第一医院麻醉科,衡阳421001 [3]南华大学医学院神经科学研究所,衡阳421001 [4]南华大学医学院病理生理学教研室,衡阳421001

出　　处：《生物化学与生物物理进展》2014年第5期487-496,共10页Progress In Biochemistry and Biophysics

基　　金：supported by grants from The National Natural Science Foundation of China(81200985,81071005);Natural Science Foundation of Hunan Province,China(11JJ3117);the Scientific Research Foundation for the Returned Overseas Chinese Scholars,State Education Ministry(2011508)~~

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.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 NariS （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 H^S 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-l-dependant manner. Our findings suggest a promising role of PON-1 as a novel therapeutic target for neuronal damage after FA exposure.

关 键 词：甲醛 硫化氢 PARAOXONASE-1 凋亡 活性氧 

分 类 号：R338[医药卫生—人体生理学] R74[医药卫生—基础医学]