PMID- 24685639 OWN - NLM STAT- MEDLINE DCOM- 20150128 LR - 20181202 IS - 1879-0712 (Electronic) IS - 0014-2999 (Linking) VI - 734 DP - 2014 Jul 5 TI - N-terminal 5-mer peptide analog P165 of amyloid precursor protein inhibits UVA-induced MMP-1 expression by suppressing the MAPK pathway in human dermal fibroblasts. PG - 1-8 LID - S0014-2999(14)00234-9 [pii] LID - 10.1016/j.ejphar.2014.03.028 [doi] AB - Exposure to ultraviolet (UV) radiation leads to a progressive increase in dermal damage through the degradation of collagen, which is mediated by matrix metalloproteinases (MMPs). UV radiation alters the intracellular signaling events that regulate the elaboration of MMPs. Our previous study showed that P165, the N-terminal 5-mer peptide analog of amyloid precursor protein, exerts a protective effect on ultraviolet A (UVA)-induced loss of collagen type I in human dermal fibroblasts (HDFs) by inhibiting the generation of intracellular reactive oxygen species and MMP-1. In this study, we focused on specific signal transduction pathways to elucidate the possible photoprotective mechanisms of P165 in controlling MMP-1 inhibition. Results from western blot analyses indicated that pretreatment with P165 dose-dependently inhibited UVA-induced phosphorylation of extracellular regulated protein kinases (ERK), c-Jun N-terminal kniase (JNK), p38 mitogen-activated protein kinases (MAPKs), and the phosphorylation of their downstream targets c-Jun and c-Fos. The photoprotective effects of P165 were further demonstrated in collagen type I secretion and cellular senescence induced by UVA irradiation. These findings suggest that P165 exerts photoprotective activity in UVA-treated HDFs by regulating MMP-1 generation. This activity may be mediated by inhibiting the MAPK signaling pathways. Thus, P165 is a potential agent for the prevention of skin photoaging. CI - Copyright (c) 2014 Elsevier B.V. All rights reserved. FAU - Wang, Ying AU - Wang Y AD - Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. FAU - Chen, Hui AU - Chen H AD - Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. FAU - Wang, Wen AU - Wang W AD - Department of Pharmacology, Xuan Wu Hospital, Capital Medical University, Key laboratory for Neurodegenerative Diseases of Ministry of Education, Beijing 100053, China. FAU - Wang, Rong AU - Wang R AD - Department of Central Laboratory, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. FAU - Liu, Zi-Lian AU - Liu ZL AD - Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. FAU - Zhu, Wei AU - Zhu W AD - Department of Dermatology and Venereology, Xuan Wu Hospital, Capital Medical University, Beijing 100053, China. Electronic address: zhuwei@xwh.ccmu.edu.cn. FAU - Lian, Shi AU - Lian S AD - Department of Dermatology and Venereology, Capital Medical University, Beijing 100069, China. Electronic address: drlianshi@sina.com. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20140329 PL - Netherlands TA - Eur J Pharmacol JT - European journal of pharmacology JID - 1254354 RN - 0 (Amyloid beta-Protein Precursor) RN - 0 (Collagen Type I) RN - 0 (Oligopeptides) RN - 0 (Proto-Oncogene Proteins c-fos) RN - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases) RN - EC 3.2.1.23 (beta-Galactosidase) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Amyloid beta-Protein Precursor/*chemistry MH - Collagen Type I/metabolism MH - Enzyme Activation/drug effects/radiation effects MH - Fibroblasts/cytology/drug effects/*metabolism/radiation effects MH - Gene Expression Regulation, Enzymologic/*drug effects MH - Humans MH - JNK Mitogen-Activated Protein Kinases/metabolism MH - MAP Kinase Signaling System/*drug effects/radiation effects MH - Matrix Metalloproteinase 1/*metabolism MH - Oligopeptides/*pharmacology MH - Phosphorylation/drug effects/radiation effects MH - Proto-Oncogene Proteins c-fos/metabolism MH - Skin/cytology MH - Ultraviolet Rays/*adverse effects MH - beta-Galactosidase/metabolism OTO - NOTNLM OT - 5 peptide analog of amyloid precursor protein (P165) OT - 5-bromo-4-chloro-3-indolyl-beta-d-galactopyranoside (PubChem CID: 44629973) OT - Acrylamide (PubChem CID: 6579) OT - Glutamine (PubChem CID: 5961) OT - Glutaraldehyde (PubChem CID: 3485) OT - Human dermal fibroblasts OT - MAPKs OT - Phenylmethylsulfonyl fluoride (PubChem CID: 4784) OT - Photoaging OT - Sodium fluoride (PubChem CID: 5235) OT - Sodium orthovanadate (PubChem CID: 61671) OT - Ultraviolet A EDAT- 2014/04/02 06:00 MHDA- 2015/01/30 06:00 CRDT- 2014/04/02 06:00 PHST- 2014/02/12 00:00 [received] PHST- 2014/03/07 00:00 [revised] PHST- 2014/03/20 00:00 [accepted] PHST- 2014/04/02 06:00 [entrez] PHST- 2014/04/02 06:00 [pubmed] PHST- 2015/01/30 06:00 [medline] AID - S0014-2999(14)00234-9 [pii] AID - 10.1016/j.ejphar.2014.03.028 [doi] PST - ppublish SO - Eur J Pharmacol. 2014 Jul 5;734:1-8. doi: 10.1016/j.ejphar.2014.03.028. Epub 2014 Mar 29.