Ribeiro Thales de P, Fonseca Fernanda L, de Carvalho Mariana D C, Godinho Rodrigo M da C, de Almeida Fernando Pereira, Saint'Pierre Tatiana D, Rey Nicolás A, Fernandes Christiane, Horn Adolfo, Pereira Marcos D
Laboratório de Citotoxicidade e Genotoxicidade, Departamento de Bioquímica, Instituto de Química, Universidade Federal do Rio de Janeiro, Rio de Janeiro, RJ, Brazil.
Centro de Desenvolvimento Tecnológico em Saúde, CDTS Fiocruz, Rio de Janeiro, RJ, Brazil.
Biochem J. 2017 Jan 15;474(2):301-315. doi: 10.1042/BCJ20160480. Epub 2016 Nov 15.
Aging is a natural process characterized by several biological changes. In this context, oxidative stress appears as a key factor that leads cells and organisms to severe dysfunctions and diseases. To cope with reactive oxygen species and oxidative-related damage, there has been increased use of superoxide dismutase (SOD)/catalase (CAT) biomimetic compounds. Recently, we have shown that three metal-based compounds {[Fe(HPClNOL)Cl]NO, Cu(HPClNOL)(CHCN) and Mn(HPClNOL)(Cl)}, harboring in vitro SOD and/or CAT activities, were critical for protection of yeast cells against oxidative stress. In this work, treating Saccharomyces cerevisiae with these SOD/CAT mimics (25.0 µM/1 h), we highlight the pivotal role of these compounds to extend the life span of yeast during chronological aging. Evaluating lipid and protein oxidation of aged cells, it becomes evident that these mimics extend the life expectancy of yeast mainly due to the reduction in oxidative stress biomarkers. In addition, the treatment of yeast cells with these mimics regulated the amounts of lipid droplet occurrence, consistent with the requirement and protection of lipids for cell integrity during aging. Concerning SOD/CAT mimics uptake, using inductively coupled plasma mass spectrometry, we add new evidence that these complexes, besides being bioabsorbed by S. cerevisiae cells, can also affect metal homeostasis. Finally, our work presents a new application for these SOD/CAT mimics, which demonstrate a great potential to be employed as antiaging agents. Taken together, these promising results prompt future studies concerning the relevance of administration of these molecules against the emerging aging-related diseases such as Parkinson's, Alzheimer's and Huntington's.
衰老 是一个以多种生物学变化为特征的自然过程。在这种情况下,氧化应激似乎是导致细胞和生物体出现严重功能障碍和疾病的关键因素。为了应对活性氧和氧化相关损伤,超氧化物歧化酶(SOD)/过氧化氢酶(CAT)仿生化合物的使用越来越多。最近,我们发现三种具有体外SOD和/或CAT活性的金属基化合物{[Fe(HPClNOL)Cl]NO、Cu(HPClNOL)(CHCN)和Mn(HPClNOL)(Cl)}对于保护酵母细胞免受氧化应激至关重要。在这项工作中,用这些SOD/CAT模拟物(25.0 μM/1小时)处理酿酒酵母,我们强调了这些化合物在延长酵母在时序性衰老过程中的寿命方面的关键作用。评估衰老细胞的脂质和蛋白质氧化,很明显这些模拟物延长酵母的预期寿命主要是由于氧化应激生物标志物的减少。此外,用这些模拟物处理酵母细胞调节了脂滴出现的数量,这与衰老过程中细胞完整性对脂质的需求和保护一致。关于SOD/CAT模拟物的摄取,使用电感耦合等离子体质谱法,我们提供了新的证据,表明这些复合物除了被酿酒酵母细胞生物吸收外,还会影响金属稳态。最后,我们的工作展示了这些SOD/CAT模拟物的一种新应用,它们显示出作为抗衰老剂的巨大潜力。综上所述,这些有前景的结果促使未来开展关于这些分子在对抗帕金森氏症、阿尔茨海默氏症和亨廷顿氏症等新兴衰老相关疾病方面给药相关性的研究。