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

Abstract

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.

• Authors: Ziqiang Wang, Ning Han, Kunxiao Zhao, Ying Li, Yanqing Chi, Baoxing Wang
• Journal: International immunopharmacology (Int Immunopharmacol) Vol. 72 Pg. 445-453 (Jul 2019) ISSN: 1878-1705 [Electronic] Netherlands
• PMID: 31035086 (Publication Type: Journal Article)
• Copyright: Copyright © 2019 Elsevier B.V. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Antioxidants
• KEAP1 protein, human
• Kelch-Like ECH-Associated Protein 1
• NF-E2-Related Factor 2
• NFE2L2 protein, human
• Pyrroles
• Quinolines
• pyrroloquinoline

Topics

• Anti-Inflammatory Agents (pharmacology)
• Antioxidants (pharmacology)
• Cell Line
• Cellular Senescence (drug effects)
• Epithelial Cells (drug effects, metabolism)
• Humans
• Kelch-Like ECH-Associated Protein 1 (metabolism)
• Kidney (cytology)
• NF-E2-Related Factor 2 (metabolism)
• Oxidative Stress (drug effects)
• Pyrroles (pharmacology)
• Quinolines (pharmacology)
• Signal Transduction (drug effects)