SEPS1 protects RAW264.7 cells from pharmacological ER stress agent-induced apoptosis.
Selenoprotein S (SEPS1) is a novel endoplasmic reticulum (ER) resident protein and it is known to play an important role in production of inflammatory cytokines. Here, we show evidence that SEPS1 is stimulated by pharmacological ER stress agents in RAW264.7 macrophages as well as other cell types. Overexpression studies reveal a protective action of SEPS1 in macrophages against ER stress-induced cytotoxicity and apoptosis, resulting in promoting cell survival during ER stress. The protective action of SEPS1 is largely dependent on ER stress-mediated cell death signal with less effect on non-ER stress component cell death signals. Conversely, suppression of SEPS1 in macrophages results in sensitization of cells to ER stress-induced cell death. These findings suggest that SEPS1 could be a new ER stress-dependent survival factor that protects macrophage against ER stress-induced cellular dysfunction.
Kim
Kee-Hong
KH
Division of Endocrinology, Metabolism and Clinical Nutrition, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI 53226, USA. kkim@mcw.edu
Gao
Yuan
Y
Walder
Ken
K
Collier
Greg R
GR
Skelton
Joseph
J
Kissebah
Ahmed H
AH
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism*; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D051140:Selenoproteins / Q000378:metabolism*; D019284:Thapsigargin / Q000494:pharmacology*; D014415:Tunicamycin / Q000494:pharmacology*
D008565:Membrane Proteins; C487710:SELENOS protein, human; D051140:Selenoproteins; D014415:Tunicamycin; D019284:Thapsigargin