Departamento de Biologia Experimental, Faculdade de Medicina da Universidade do Porto, 4200-319, Portugal.
Free Radic Biol Med. 2012 Aug 15;53(4):916-25. doi: 10.1016/j.freeradbiomed.2012.06.005. Epub 2012 Jun 15.
Protein carbonylation is a common feature in cells exposed to oxidants, leading to protein dysfunction and protein aggregates. Actin, which is involved in manifold cellular processes, is a sensitive target protein to this oxidative modification. T-cell proteins have been widely described to be sensitive targets to oxidative modifications. The aim of this work was to test whether the formation of protein aggregates contributes to the impaired proliferation of Jurkat cells after oxidative stress and to test whether actin as a major oxidation-prone cytoskeletal protein is an integral part of such protein aggregates. We used Jurkat cells, an established T-cell model, showing the formation of actin aggregates along with the decrease of proteasome activity. The presence of these protein aggregates inhibits Jurkat proliferation even under conditions not influencing viability. As a conclusion, we propose that an oxidative environment leads to actin aggregates contributing to T-cell cellular functional impairment.
蛋白质羰基化是细胞暴露于氧化剂时的常见特征，导致蛋白质功能障碍和蛋白质聚集。肌动蛋白参与多种细胞过程，是这种氧化修饰的敏感靶蛋白。T 细胞蛋白已被广泛描述为易受氧化修饰影响的敏感靶蛋白。这项工作的目的是测试在氧化应激后，蛋白质聚集体的形成是否导致 Jurkat 细胞增殖受损，并测试肌动蛋白作为主要易氧化细胞骨架蛋白是否是这种蛋白质聚集体的组成部分。我们使用了 Jurkat 细胞，这是一种已建立的 T 细胞模型，显示了肌动蛋白聚集体的形成，同时伴随着蛋白酶体活性的降低。即使在不影响生存力的条件下，这些蛋白质聚集体的存在也会抑制 Jurkat 增殖。因此，我们提出，氧化环境会导致肌动蛋白聚集体导致 T 细胞细胞功能障碍。
