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J Pharmacol Exp Ther ; 360(3): 388-398, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28011874

RESUMO

UVA irradiation plays a role in premature aging of the skin through triggering oxidative stress-associated stimulation of matrix metalloproteinase-1 (MMP-1) responsible for collagen degradation, a hallmark of photoaged skin. Compounds that can activate nuclear factor E2-related factor 2 (Nrf2), a transcription factor regulating antioxidant gene expression, should therefore serve as effective antiphotoaging agents. We investigated whether genetic silencing of Nrf2 could relieve UVA-mediated MMP-1 upregulation via activation of mitogen-activated protein kinase (MAPK)/activator protein 1 (AP-1) signaling using human keratinocyte cell line (HaCaT). Antiphotoaging effects of hispidulin (HPD) and sulforaphane (SFN) were assessed on their abilities to activate Nrf2 in controlling MMP-1 and collagen expressions in association with phosphorylation of MAPKs (extracellular signal-regulated kinase, c-Jun N-terminal kinase, and p38), c-Jun, and c-Fos, using the skin of BALB/c mice subjected to repetitive UVA irradiation. Our findings suggested that depletion of Nrf2 promoted both mRNA expression and activity of MMP-1 in the UVA-irradiated HaCaT cells. Treatment of Nrf2 knocked-down HaCaT cells with MAPK inhibitors significantly suppressed UVA-induced MMP-1 and AP-1 activities. Moreover, pretreatment of the mouse skin with HPD and SFN, which could activate Nrf2, provided protective effects against UVA-mediated MMP-1 induction and collagen depletion in correlation with the decreased levels of phosphorylated MAPKs, c-Jun, and c-Fos in the mouse skin. In conclusion, Nrf2 could influence UVA-mediated MMP-1 upregulation through the MAPK/AP-1 signaling cascades. HPD and SFN may therefore represent promising antiphotoaging candidates.


Assuntos
Colágeno/metabolismo , Flavonas/farmacologia , Isotiocianatos/farmacologia , Fator 2 Relacionado a NF-E2/metabolismo , Envelhecimento da Pele , Raios Ultravioleta/efeitos adversos , Senilidade Prematura/etiologia , Senilidade Prematura/metabolismo , Animais , Antimutagênicos/farmacologia , Linhagem Celular , Ativação Enzimática/efeitos da radiação , Humanos , Queratinócitos , Sistema de Sinalização das MAP Quinases/efeitos da radiação , Metaloproteinase 1 da Matriz/metabolismo , Camundongos , Estresse Oxidativo , Pele/metabolismo , Envelhecimento da Pele/efeitos dos fármacos , Envelhecimento da Pele/efeitos da radiação , Fator de Transcrição AP-1/metabolismo , Regulação para Cima/efeitos da radiação
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