title: 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.
abstract: 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/cm2. 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 β‑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/cm2 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.
authors.affiliation: Department of Clinical Research, Friendship Plastic Surgery Hospital, Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.
authors.forename: Chunli
authors.initials: C
authors.lastname: Zhang
authors.affiliation: College of Science, Nanjing Normal University, Nanjing, Jiangsu 210046, P.R. China.
authors.forename: Chuanjun
authors.initials: C
authors.lastname: Wen
authors.affiliation: Department of Plastic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Jinde
authors.initials: J
authors.lastname: Lin
authors.affiliation: Department of Plastic Surgery, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210000, P.R. China.
authors.forename: Gan
authors.initials: G
authors.lastname: Shen
mesh_terms: D017209:Apoptosis; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects / Q000528:radiation effects; D020405:Dermis / Q000166:cytology*; D005347:Fibroblasts / Q000187:drug effects / Q000502:physiology* / Q000528:radiation effects; D015870:Gene Expression; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D045542:PQQ Cofactor / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D015398:Signal Transduction; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism; D014466:Ultraviolet Rays
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D011837:Radiation-Protective Agents; D045542:PQQ Cofactor; C496541:HMOX1 protein, human; D051547:Heme Oxygenase-1; C511768:MMP3 protein, human; D019278:Matrix Metalloproteinase 3; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; C447939:SIRT1 protein, human; C516592:SIRT6 protein, human; D056564:Sirtuin 1; D037761:Sirtuins