Changes in temperature modulate heme oxygenase-1 induction by curcumin in renal epithelial cells

Abstract

The stress protein heme oxygenase-1 (HO-1) plays an essential role in the prevention of transplant-associated organ injury and rejection. Prior to transplantation, organs are normally subjected to variable periods of cold storage in appropriate preservation solutions. Here, we examined whether curcumin, a phenolic plant extract which strongly induces HO-1 in many cell types, could up-regulate HO-1 protein in cultured renal epithelial cells at temperatures lower than the physiological 37 °C. We found that stimulation of HO-1 following incubation of cells with curcumin for 6 h was dramatically reduced by decreasing the temperature from 37 to 10 °C. Interestingly, renal cells displayed high HO-1 expression and heme oxygenase activity when exposed to a programmed change in temperature that consisted of 3 h at 37 °C followed by 1.5 h at 20 °C and 1.5 h at 10 °C. Increased HO-1 levels were observed also after incubation of cells with curcumin during the programmed change in temperature under hypoxia, another feature typical of cold storage procedures. Upon challenge with an oxidant-generating system, cells pretreated with curcumin at 37 °C or during the programmed change in temperature exhibited increased resistance to oxidative stress-mediated injury. These findings highlight the feasibility of modulating HO-1 expression during hypothermic storage to confer tissues a better protection to counteract the damage characteristic of organ transplantation.