Nuclear proteasome activation and degradation of carboxymethylated histones in human keratinocytes following glyoxal treatment
摘要:
Nuclear DNA damage has been studied in detail, but much less is known concerning the occurrence and fate of nuclear protein damage. Glycoxidation, protein damage that results from a combination of protein glycation and oxidation, leads to the formation of protein-advanced glycation end products (AGE) of which N -carboxymethyllysine (CML) is a major AGE. We have used glyoxal, a product of environmental exposures that readily leads to the formation of CML, to study nuclear protein glycoxidation in HaCaT human keratinocytes. Glyoxal treatment that did not affect cell viability but inhibited cell proliferation in a dose-dependent manner that led to accumulation of CML-modified histones. Modified histones were slowly degraded but persisted for more than 3 days following treatment. Preincubation of cells with a proteasome inhibitor following glyoxal treatment led to an increase in CML-modified histones. While glyoxal treatment resulted in a slight decrease in total cellular proteasome activity, a dose dependent increase of up to 4-fold in nuclear proteasome activity was observed. The increase in nuclear proteasome activity was due to both increased nuclear proteasome protein content and increased activity, neither of which were affected by cyclohexamide. The increase also was unaffected by inhibitors of poly(ADP-ribose) polymerases, which have been previously implicated in nuclear proteasome activation by oxidizing agents. Accumulation of CML-modified histones over time may lead to epigenetic changes that contribute to various pathologies including aging and cancer, and upregulation of nuclear proteasome activity under conditions of glyoxidative stress may function to limit such damage.
展开
关键词:
AGE products advanced glycoxidation end products advanced glycoxidation end products CEL N ɛ-carboxyethyllysine N ɛ-carboxyethyllysine CML N ɛ-carboxymethyllysine N ɛ-carboxymethyllysine DMEM Dulbecco's modified Eagle's medium Dulbecco's modified Eagle's medium GOLD glyoxal lysine dimers glyoxal lysine dimers
DOI:
10.1016/j.freeradbiomed.2004.11.030
被引量:
年份:
2005
通过文献互助平台发起求助,成功后即可免费获取论文全文。
相似文献
参考文献
引证文献
辅助模式
引用
文献可以批量引用啦~
欢迎点我试用!