Identification and characterization of endoplasmic reticulum stress-induced apoptosis in vivo.
The endoplasmic reticulum (ER) is recognized primarily as the site of synthesis and folding of secreted and membrane-bound proteins. The ER provides stringent quality control systems to ensure that only correctly folded, functional proteins are released from the ER and that misfolded proteins are degraded. The efficient functioning of the ER is essential for most cellular activities and for survival. Stimuli that interfere with ER function can disrupt ER homeostasis, impose stress to the ER, and subsequently cause accumulation of unfolded or misfolded proteins in the ER lumen. ER transmembrane proteins detect the onset of ER stress and initiate highly specific signaling pathways collectively called the "unfolded protein response" (UPR) to restore normal ER functions. However, if ER homeostasis cannot be reestablished in response to intense or prolonged ER stress, the UPR induces ER stress-associated apoptosis to protect the organism by removing the stressed cells that produce misfolded or malfunctioning proteins. This chapter summarizes current understanding of ER stress-induced apoptosis and reliable methods to examine ER stress and apoptosis in mammalian cells. Since the liver is the major organ dealing with metabolic or pathological stress and is responsible for the detoxification of chemical compounds, the experimental protocols described here focus on identification and characterization of ER stress-induced apoptosis in mouse liver.
Zhang
Kezhong
K
Department of Biological Chemistry, The University of Michigan Medical Center, Ann Arbor, Michigan, USA.
Kaufman
Randal J
RJ
D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology*; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D015398:Signal Transduction / Q000502:physiology*; D014415:Tunicamycin / Q000494:pharmacology
D000900:Anti-Bacterial Agents; D014415:Tunicamycin