Skip to main content
. Author manuscript; available in PMC: 2013 May 5.
Published in final edited form as: Eur J Pharmacol. 2012 Feb 22;682(1-3):12–20. doi: 10.1016/j.ejphar.2012.01.030

Figure 6.

Figure 6

Putative model for the mechanism of sigma-1 receptor mediated protection against cellular oxidative stress. ER stress or ER calcium drop leads to accumulation of unfolded proteins. Sigma-1 receptor functions as an ER chaperone to protect against ER stress and increase calcium mobilization from ER to mitochondria by stabilizing IP3 receptor(Hayashi and Su, 2007). Calcium influx into the mitochondria leads to increase ATP generation(Brookes et al., 2004) to counteract ATP demand for chaperoning function. Simultaneously, mitochondria also produce more reactive oxygen species (ROS) due to more respiratory chain electron leakage (Brookes et al., 2004). In addition, correct protein folding is an oxidative process, which also increases cellular oxidative stress(Cuozzo and Kaiser, 1999). Sigma-1 receptors counteract cellular oxidative stress by up regulation of antioxidant genes such as SOD1 and NQO1, through the activation of Antioxidant Response Elements (ARE).