期刊
JOURNAL OF BIOLOGICAL CHEMISTRY
卷 286, 期 40, 页码 34903-34913出版社
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
DOI: 10.1074/jbc.M111.279190
关键词
-
资金
- Defense Research and Development Organization (DRDO), Government of India
- Centre for DNA Fingerprinting and Diagnostics (CDFD)
- Indian Council for Medical Research (ICMR), Government of India
- Council for Scientific and Industrial Research (CSIR), Government of India
Advanced glycation end products (AGEs) accumulate in diabetic patients due to high blood glucose levels and cause multiple deleterious effects. In this study, we provide evidence that the AGE increased cell death, one such deleterious effect. Methyl glyoxal-coupled human serum albumin (AGE-HSA) induced transcription factors such as NF-kappa B, NF-AT, and AP-1. AGE acts through its cell surface receptor, RAGE, and degranulates vesicular contents including interleukin-8 (IL-8). The number of RAGEs, as well as the amount of NF-kappa B activation, is low, but the cell death is higher in neuronal cells upon AGE treatment. Degranulated IL-8 acts through its receptors, IL-8Rs, and induces sequential events in cells: increase in intracellular Ca2+, activation of calcineurin, dephosphorylation of cytoplasmic NF-AT, nuclear translocation of NF-AT, and expression of FasL. Expressed FasL increases activity of caspases and induces cell death. Although AGE increases the amount of reactive oxygen intermediate, accompanying cell death is not dependent upon reactive oxygen intermediate. AGE induces autophagy, which partially protects cells from cell death. A novel mechanism of AGE-mediated cell death in different cell types, especially in neuronal cells where it is an early event, is provided here. Thus, this study may be important in several age-related neuronal diseases where AGE-induced apoptosis is observed because of high amounts of AGE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据