Laboratory of Experimental Neurology, Fondazione Santa Lucia IRCCS, Rome, Italy.
Br J Pharmacol. 2012 Jun;166(4):1211-24. doi: 10.1111/j.1476-5381.2012.01912.x.
For many years after its discovery, hydrogen peroxide (H₂O₂) was viewed as a toxic molecule to human tissues; however, in light of recent findings, it is being recognized as an ubiquitous endogenous molecule of life as its biological role has been better elucidated. Indeed, increasing evidence suggests that H₂O₂ may act as a second messenger with a pro-survival role in several physiological processes. In addition, our group has recently demonstrated neuroprotective effects of H₂O₂ on in vitro and in vivo ischaemic models through a catalase (CAT) enzyme-mediated mechanism. Therefore, the present review summarizes experimental data supporting a neuroprotective potential of H₂O₂ in ischaemic stroke that has been principally achieved by means of pharmacological and genetic strategies that modify either the activity or the expression of the superoxide dismutase (SOD), glutathione peroxidase (GPx) and CAT enzymes, which are key regulators of H₂O₂ metabolism. It also critically discusses a translational impact concerning the role played by H₂O₂ in ischaemic stroke. Based on these data, we hope that further research will be done in order to better understand the mechanisms underlying H₂O₂ functions and to promote successful H₂O₂ signalling based therapy in ischaemic stroke.
多年来，过氧化氢 (H₂O₂) 在被发现后一直被视为对人体组织有毒的分子；然而，鉴于最近的发现，它被认为是一种无处不在的内源性生命分子，因为其生物学作用得到了更好的阐明。事实上，越来越多的证据表明，H₂O₂ 可能作为第二信使发挥作用，在几种生理过程中具有促进生存的作用。此外，我们的研究小组最近通过 CAT 酶介导的机制，在体外和体内缺血模型中证明了 H₂O₂ 的神经保护作用。因此，本综述总结了支持 H₂O₂ 在缺血性中风中具有神经保护潜力的实验数据，这些数据主要通过药理学和遗传学策略实现，这些策略可以改变超氧化物歧化酶 (SOD)、谷胱甘肽过氧化物酶 (GPx) 和 CAT 酶的活性或表达，这些酶是 H₂O₂ 代谢的关键调节剂。它还批判性地讨论了与 H₂O₂ 在缺血性中风中发挥的作用相关的转化影响。基于这些数据，我们希望进一步开展研究，以更好地理解 H₂O₂ 功能的机制，并促进基于 H₂O₂ 信号的缺血性中风治疗的成功。
