| First Author | Homma T | Year | 2015 |
| Journal | Arch Biochem Biophys | Volume | 583 |
| Pages | 65-72 | PubMed ID | 26264915 |
| Mgi Jnum | J:230764 | Mgi Id | MGI:5763721 |
| Doi | 10.1016/j.abb.2015.07.023 | Citation | Homma T, et al. (2015) SOD1 deficiency decreases proteasomal function, leading to the accumulation of ubiquitinated proteins in erythrocytes. Arch Biochem Biophys 583:65-72 |
| abstractText | We previously demonstrated that elevated levels of ROS in red blood cells (RBCs) are responsible for anemia in SOD1-deficient mice, suggesting that the oxidative stress-induced massive destruction of RBCs is an underlying mechanism for autoimmune hemolytic anemia. In the current study, we examined the issue of how elevated ROS are involved in the destruction of RBCs and the onset of anemia from the view point of the proteolytic removal of oxidatively-damaged proteins. We found that poly-ubiquitinated proteins had accumulated and had undergone aggregation in RBCs from SOD1-deficient mice and from phenylhydrazine-induced anemic mice. Although the protein levels of the three catalytic components of the proteasome, beta1, beta2, and beta5, were not significantly altered, their proteolytic activities were decreased in the SOD1-deficient RBCs. These data suggest that oxidative-stress triggers the dysfunction of the proteasomal system, which results in the accumulation of the aggregation of poly-ubiquitinated proteins. We conclude that an oxidative stress-induced malfunction in the scavenging activity of proteasomes accelerates the accumulation of damaged proteins, leading to a shortened lifespan of RBCs and, hence, anemia. |
