Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders.
Lipid Peroxidation-Derived Aldehydes, 4-Hydroxynonenal and Malondialdehyde in Aging-Related Disorders.
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DOI：
10.3390/antiox7080102
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发表时间：
2018-07-30
期刊：
影响因子：
--
通讯作者：
Gentile F
中科院分区：
文献类型：
--
作者：
Barrera G;Pizzimenti S;Daga M;Dianzani C;Arcaro A;Cetrangolo GP;Giordano G;Cucci MA;Graf M;Gentile F
在衰老的各种机制中，很早就有人提出氧化应激起着重要的作用。后者引起生物大分子，如DNA、脂肪和蛋白质的结构损伤的一个主要方式是通过加剧膜脂的过氧化，导致几种反应性醛的产生。脂质过氧化衍生的醛不仅可以通过与生物大分子形成共价亲电加成产物来修饰生物大分子，而且还可以作为氧化应激的第二信使，具有相对延长的寿命。随着年龄的增长，它们的作用可能会进一步增强，因为它们在细胞和生物液中的浓度随着年龄的增长而增加。由于脂质过氧化衍生的醛，特别是4-羟基壬烯醛(HNE)在神经退行性变、炎症和癌症中的参与和作用已在最近的几篇优秀综述中进行了讨论，在当前的一篇综述中，我们重点讨论了反应性醛在其他与年龄相关的疾病中的参与：骨量减少、骨量减少、免疫衰老和骨髓增生异常综合征。在这些以氧化应激增加为特征的衰老相关疾病中，HNE和丙二醛(MDA)都起着重要的致病作用。这些醛，特别是HNE，可以与循环或细胞中具有重要功能的蛋白质形成加合物，如参与肌肉细胞凋亡的蛋白质，从而导致它们的功能衰退，加速它们的分子周转和功能。我们认为，在年龄相关疾病中观察到的毒性效应的很大一部分可能取决于醛-蛋白质加合物的形成。新的氧化还原蛋白质组学方法，定位于氧化应激过程中产生的醛对不同细胞蛋白质的修饰，应扩展到这些年龄相关疾病，为制定有针对性的治疗策略铺平道路，旨在减轻与这些疾病相关的发病率和死亡率负担。
Among the various mechanisms involved in aging, it was proposed long ago that a prominent role is played by oxidative stress. A major way by which the latter can provoke structural damage to biological macromolecules, such as DNA, lipids, and proteins, is by fueling the peroxidation of membrane lipids, leading to the production of several reactive aldehydes. Lipid peroxidation-derived aldehydes can not only modify biological macromolecules, by forming covalent electrophilic addition products with them, but also act as second messengers of oxidative stress, having relatively extended lifespans. Their effects might be further enhanced with aging, as their concentrations in cells and biological fluids increase with age. Since the involvement and the role of lipid peroxidation-derived aldehydes, particularly of 4-hydroxynonenal (HNE), in neurodegenerations, inflammation, and cancer, has been discussed in several excellent recent reviews, in the present one we focus on the involvement of reactive aldehydes in other age-related disorders: osteopenia, sarcopenia, immunosenescence and myelodysplastic syndromes. In these aging-related disorders, characterized by increases of oxidative stress, both HNE and malondialdehyde (MDA) play important pathogenic roles. These aldehydes, and HNE in particular, can form adducts with circulating or cellular proteins of critical functional importance, such as the proteins involved in apoptosis in muscle cells, thus leading to their functional decay and acceleration of their molecular turnover and functionality. We suggest that a major fraction of the toxic effects observed in age-related disorders could depend on the formation of aldehyde-protein adducts. New redox proteomic approaches, pinpointing the modifications of distinct cell proteins by the aldehydes generated in the course of oxidative stress, should be extended to these age-associated disorders, to pave the way to targeted therapeutic strategies, aiming to alleviate the burden of morbidity and mortality associated with these disturbances.
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影响因子：
--
作者：
Espino J;Pariente JA;Rodríguez AB
通讯作者：
Rodríguez AB
DOI：
10.1111/j.1749-6632.2002.tb02111.x
发表时间：
2002-01-01
期刊：
INCREASING HEALTHY LIFE SPAN: CONVENTIONAL MEASURES AND SLOWING THE INNATE AGING PROCESS
影响因子：
--
作者：
Aiken, J;Bua, E;McKiernan, S
通讯作者：
McKiernan, S
影响因子：
3.1
作者：
Brioche, Thomas;Lemoine-Morel, Sophie
通讯作者：
Lemoine-Morel, Sophie
影响因子：
7.2
作者：
Braga, Melissa;Hikim, Amiya P. Sinha;Sinha-Hikim, Indrani
通讯作者：
Sinha-Hikim, Indrani
影响因子：
4.1
作者：
BOVERIS, A;CHANCE, B
通讯作者：
CHANCE, B