Protective effect of pyrroloquinoline quinine on ultraviolet A irradiation-induced human dermal fibroblast senescence in vitro proceeds via the anti-apoptotic sirtuin 1/nuclear factor-derived erythroid 2-related factor 2/heme oxygenase 1 pathway

The aim of the present study was to determine whether pyrroloquinoline quinine (PQQ) exerts a protective effect on ultraviolet A (UVA) irradiation-induced senescence in human dermal fibroblasts (HDFs) and to elucidate its mechanism of action in vitro. A senescence model was constructed as follows: HDFs (1x10(4)-1x10(6)) were cultured in a six-well plate in vitro and then exposed to UVA irradiation at a dosage of 9 J/cm(2). Various concentrations of PQQ (50, 100 and 200 ng/ml) were added to the culture medium 24 h prior to UVA exposure. Following 72 h of irradiation, senescence-associated beta-galactosidase staining was performed in order to evaluate the senescence state. Furthermore, mRNA expression of the senescence marker genes matrix-metalloprotease (MMP) 1 and MMP3 was determined using reverse transcription quantitative polymerase chain reaction. Protein expression of sirtuin (SIRT) 1, SIRT6, nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase 1 (HO-1) were detected using western blot analysis. The results showed that the percentage of cells stained by X-gal following 9 J/cm(2) UVA irradiation was markedly increased compared with that of the control group (53 and 8%, respectively), while 50 ng/ml PQQ attenuated the ratio of positive staining compared with that of the UVA-only cells (29 vs. 53%, respectively). Expression of fibroblast senescence marker genes MMP1 and MMP3 was decreased in cells treated with UVA and 50 ng/ml PQQ compared with that of cells in the UVA-only group. Western blot analysis revealed significant effects of PQQ on SIRT1 and SIRT6. Nrf2 and HO-1 exbibited mild changes with the same trend when treated with or without UVA and PQQ. In conclusion, the results of the present study showed that pyrroloquinoline quinine may have a protective effect on UVA irradiation-induced HDF aging, which may be associated with the anti-apoptotic SIRT1/Nrf2/HO-1 pathway as well as SIRT6 signaling.