Abstract: Objective: This study aimed to elucidate the role of curcumin as an incomplete promoter of Na/K-ATPase (NKA) in protecting cells from hypoxia/reoxygenation (H/R)-induced injury by inducing the activation of the NKA/steroid receptor coactivator (Src) receptor complex. Methods: The effects of curcumin on the activity and conformation of NKA were determined by NKA screening test. An H/R model was used to simulate oxidative damage in cells. After LLC-PK1 cells were pre-protected with curcumin for 1 h and then treated with hypoxia for 1 h followed by reoxygenation for 3 h, the activity of extracellular lactate dehydrogenase (LDH), cell viability, and the expression levels of Src, phosphorylated steroid receptor coactivator (p-Src), extracellular signal-regulated protein kinases (Erk) and phosphorylated extracellular signal-regulated protein kinases (p-Erk) were examined. Results: Curcumin could inhibit the activity of NKA, change its conformation and activate the NKA/Src signaling pathway through increasing the phosphorylation levels of Src and Erk1/2. However, the co-existence of curcumin and ouabain could increase the activity of NKA and inhibit the over-activation of the NKA/Src signaling pathway. Curcumin attenuated oxidative stress-induced injury in LLC-PK1 cells, decreased the level of LDH activity, increased cell viability, and effectively lowered the expression levels of p-Src and p-Erk. Conclusion: Curcumin has a bi-directional regulatory effect on the NKA/Src signaling pathway. It could protect cells from H/R by inducing the activation of the NKA/Src receptor complex.

Key words: curcumin; Na/K-ATPase; steroid receptor coactivator kinase; extracellular signal-regulated protein kinases; oxidative damage