期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2004
卷号：101
期号：32
页码：11560-11565
DOI：10.1073/pnas.0404101101
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：On reaching maturity, animal organs cease to increase in size because of inhibition of cell replication activities. It follows that maintenance of optimal organ function depends on the elimination of oxidatively damaged cells and their replacement with new cells. To examine the effects of oxidative stress and apoptosis on the accumulation of oxidized proteins, we exposed acute promyelocytic leukemia cells to arsenic trioxide (As2O3) in the presence and absence of a general caspase inhibitor (benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone), which is known to inhibit caspase-induced apoptosis. We confirm that treatment of cells with As2O3 induces apoptosis and leads to the accumulation of oxidized proteins. Furthermore, inhibition of caspase activities prevented As2O3-induced apoptosis and led to a substantial increase in accumulation of oxidized proteins. Moreover, inhibition of caspase activity in the absence of As2O3 led to elevated levels of the LMP2 immunoproteasome protein. We also show that caspase inhibition leads to increases in the levels of oxidized proteins obtained by treatments with hydrogen peroxide plus ferrous iron. Collectively, these results suggest the possibility that an age-related loss in capacity to carry out apoptosis might contribute to the observed accumulation of oxidized proteins during aging and in age-related diseases.
关键词：arsenic trioxide ; programmed cell death ; protein carbonyl NB4 cells ; H2O2
