Departamento de Bioquímica, Universidade de São Paulo, 05508-900 Cidade Universitária, São Paulo, Brazil.
Free Radic Biol Med. 2011 Aug 1;51(3):664-70. doi: 10.1016/j.freeradbiomed.2011.05.035. Epub 2011 Jun 6.
The ubiquitin-proteasome system governs the half-life of most cellular proteins. Calorie restriction (CR) extends the maximum life span of a variety of species and prevents oxidized protein accumulation. We studied the effects of CR on the ubiquitin-proteasome system and protein turnover in aging Saccharomyces cerevisiae. CR increased chronological life span as well as proteasome activity compared to control cells. The levels of protein carbonyls, a marker of protein oxidation, and those of polyubiquitinated proteins were modulated by CR. Controls, but not CR cells, exhibited a significant increase in oxidized proteins. In keeping with decreased proteasome activity, polyubiquitinated proteins were increased in young control cells compared to time-matched CR cells, but were profoundly decreased in aged control cells despite decreased proteasomal activity. This finding is related to a decreased polyubiquitination ability due to the impairment of the ubiquitin-activating enzyme in aged control cells, probably related to a more oxidative microenvironment. CR preserves the ubiquitin-proteasome system activity. Overall, we found that aging and CR modulate many aspects of protein modification and turnover.
泛素-蛋白酶体系统控制着大多数细胞蛋白的半衰期。热量限制（CR）延长了多种物种的最大寿命，并防止了氧化蛋白的积累。我们研究了 CR 对衰老酿酒酵母中泛素-蛋白酶体系统和蛋白质周转的影响。与对照细胞相比，CR 增加了生物钟寿命和蛋白酶体活性。CR 调节了蛋白质羰基（蛋白质氧化的标志物）和多聚泛素化蛋白的水平。对照细胞，但不是 CR 细胞，表现出氧化蛋白的显著增加。与蛋白酶体活性降低一致，与时间匹配的 CR 细胞相比，年轻的对照细胞中的多聚泛素化蛋白增加，但尽管蛋白酶体活性降低，老年对照细胞中的多聚泛素化蛋白却大大减少。这一发现与由于老化对照细胞中泛素激活酶的损伤导致的多泛素化能力下降有关，这可能与更氧化的微环境有关。CR 保持了泛素-蛋白酶体系统的活性。总的来说，我们发现衰老和 CR 调节了蛋白质修饰和周转的许多方面。
