Lipid rafts and oxidative stress-induced cell death.
Reactive oxygen species (ROS) are generated in response to a number of physiologic or pathologic conditions. In addition to ROS produced extrinsically, a cell may produce ROS as a result of normal metabolism and signaling processes. When sufficient quantities of ROS are present within the cell, this oxidative stress may have profound effects on the cell, including the induction of cell death. Various signaling pathways are initiated in response to oxidative stress, through which the cell's demise is assured. Many of these signaling pathways involve cholesterol-enriched domains of the cell membrane known as lipid rafts. These lipid rafts are platforms for initiation or transduction of the signal and may modulate protein activity through a direct change in local membrane structure or by allowing protein-protein interactions to occur with higher affinity/specificity or both. Among the examples discussed in this review are death-receptor signaling, induction of membrane-associated tyrosine kinase activation, and activation of transient receptor protein (TRP) channels. Special attention also is given to the RIP1/TRAF2 pathway, which involves the downstream activation of the stress-activated protein kinase JNK. The activation of the JNK pathway plays a key role in the induction of cellular death in response to ROS.
Morgan
Michael J
MJ
Cell and Cancer Biology Branch, Center for Cancer Research, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA.
Kim
You-Sun
YS
Liu
Zhenggang
Z
D000818:Animals; D016923:Cell Death / Q000502:physiology*; D002468:Cell Physiological Phenomena; D006801:Humans; D021962:Membrane Microdomains / Q000502:physiology*; D008954:Models, Biological; D018384:Oxidative Stress / Q000502:physiology*; D011494:Protein Kinases / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism
D017382:Reactive Oxygen Species; D011494:Protein Kinases