Inhibition of UVA irradiation-modulated signaling pathways by rutaecarpine, a quinazolinocarboline alkaloid, in human keratinocytes.
Matrix metalloproteinases (MMPs), a key component in photoaging of the skin due to exposure to ultraviolet A, appear to be increased by ultraviolet A irradiation-associated generation of reactive oxygen species. In this study, we investigated the effects of synthetic rutaecarpine, which is also found in Evodia rutaecarpa, on the ultraviolet A-induced changes in the expression of gelatinases: matrix metalloproteinase (MMP)-2 and MMP-9 using HaCaT human keratinocytes as a model cellular system. Ultraviolet A irradiation of HaCaT cells increased the gelatinolytic activities of MMP-2 and MMP-9, which was significantly suppressed by the pretreatment with rutaecarpine. In addition, rutaecarpine significantly suppressed the ultraviolet A-induced enhanced expression of MMP-2 and MMP-9 proteins and mRNAs. Rutaecarpine also inhibited the H2O2-induced increase in the expression of MMP-2 and MMP-9. Furthermore, rutaecarpine decreased the ultraviolet A-induced increased generation of reactive oxygen species. Taken together, these results suggest that rutaecarpine inhibited ultraviolet A-induced reactive oxygen species generation, resulting in the enhanced expression of MMP-2 and MMP-9 in human skin cells. These results further suggest that ruetaecarpine may be useful in the prevention of ultraviolet A-induced photoaging.
Beak
Sung-Mok
SM
College of Pharmacy, Yeungnam University, Gyongsan 712-749, South Korea.
Paek
Seung-Hwan
SH
Jahng
Yurngdong
Y
Lee
Yong Soo
YS
Kim
Jung-Ae
JA
D000111:Acetylcysteine / Q000494:pharmacology; D000470:Alkaloids / Q000494:pharmacology*; D015153:Blotting, Western; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D004789:Enzyme Activation / Q000187:drug effects / Q000528:radiation effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D026121:Indole Alkaloids; D015603:Keratinocytes / Q000187:drug effects* / Q000378:metabolism / Q000528:radiation effects; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D011799:Quinazolines; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000187:drug effects* / Q000528:radiation effects; D014212:Tretinoin / Q000494:pharmacology; D014466:Ultraviolet Rays; D052999:Quinazolinones
D000111:Acetylcysteine; D000470:Alkaloids; D006861:Hydrogen Peroxide; D026121:Indole Alkaloids; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D011799:Quinazolines; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D014212:Tretinoin; C028632:rutecarpine; D052999:Quinazolinones