Protective effects of pyrroloquinoline quinine against oxidative stress-induced cellular senescence and inflammation in human renal tubular epithelial cells via Keap1/Nrf2 signaling pathway.

Oxidative stress-induced cellular senescence and inflammation are important biological events in diabetic nephropathy (DN). Our recent studies have found that pyrroloquinoline quinine (PQQ) has protective effects against HG-induced oxidative stress damage and apoptosis in HK-2 cells. Nevertheless, whether PPQ has the effect of anti-inflammation and anti-senescence in HK-2 cells remains unclear. Here, we showed that low-dose PPQ treatment (100 nM) downregulates the expression of P16, P21, IL-1β, TNF-α and NF-κB in HG cultured HK-2 cells. A low dose of PPQ also upregulated the protein expression of SOD2, CAT and inhibited the generation of ROS. We also indicated that PPQ affected the activity of Keap1/Nrf2 pathway, increased the nuclear accumulation of Nrf2 and the downstream pathway protein expression of Keap1/Nrf2 signaling pathway (HO-1, NQO-1, GST and GPx-3). When ML385 was added to inhibit the activity of Keap1/Nrf2 signaling pathway, the effects of PPQ on anti-oxidative stress, anti-inflammation and anti-senescence in HK-2 cells under HG condition were weakened. In conclusion, our results suggest that PPQ could modulate HG-induced inflammation and senescence in HK-2 cells via the inhibition of ROS generation and achieves the protective effects through Keap1/Nrf2 pathway and upregulating the expression of its target protein.