ER stress inducer, thapsigargin, decreases extracellular-superoxide dismutase through MEK/ERK signalling cascades in COS7 cells

Free Radic Res. 2011 Jun;45(6):692-8. doi: 10.3109/10715762.2011.567985. Epub 2011 Mar 21.


It has been reported that tubular cells suffer an endoplasmic reticulum (ER) stress during the development of chronic kidney disease, which is a potent risk factor of cardiovascular disease. Moreover, under these conditions, reactive oxygen species are generated and induce cell injury. Extracellular-superoxide dismutase (EC-SOD) is a member of SODs and protects the cells from oxidative stress. Here, it is demonstrated that thapsigargin, an ER stress inducer, decreased EC-SOD expression, whereas the expression of Cu,Zn-SOD and Mn-SOD was not changed. On the other hand, another ER stress inducer, tunicamycin, did not affect the expression of EC-SOD. Further, it was shown that thapsigargin has the ability to activate extracellular-signal regulated kinase (ERK), but tunicamycin does not. Moreover, pre-treatment with U0126, an inhibitor of mitogen-activated protein kinase kinase (MEK)/ERK, suppressed thapsigargin-triggered EC-SOD reduction, suggesting that MEK/ERK signalling should play an important role in the regulation of EC-SOD in COS7 cells under ER stress conditions.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • COS Cells
  • Cell Hypoxia
  • Chlorocebus aethiops
  • Endoplasmic Reticulum / physiology*
  • Heat-Shock Proteins / genetics
  • Heat-Shock Proteins / metabolism
  • MAP Kinase Signaling System*
  • Mitogen-Activated Protein Kinases / metabolism*
  • Stress, Physiological*
  • Superoxide Dismutase / genetics
  • Superoxide Dismutase / metabolism*
  • Thapsigargin / pharmacology*
  • Transcription Factor CHOP / metabolism
  • Transcription, Genetic / drug effects
  • Tunicamycin / pharmacology


  • Heat-Shock Proteins
  • Tunicamycin
  • Transcription Factor CHOP
  • Thapsigargin
  • Superoxide Dismutase
  • Mitogen-Activated Protein Kinases
  • molecular chaperone GRP78