PMID- 30621167 OWN - NLM STAT- MEDLINE DCOM- 20190408 LR - 20200225 IS - 1422-0067 (Electronic) IS - 1422-0067 (Linking) VI - 20 IP - 1 DP - 2019 Jan 4 TI - Protective Effects and Mechanisms of N-Phenethyl Caffeamide from UVA-Induced Skin Damage in Human Epidermal Keratinocytes through Nrf2/HO-1 Regulation. LID - 10.3390/ijms20010164 [doi] LID - 164 AB - The skin provides an effective barrier against physical, chemical, and microbial invasion; however, overexposure to ultraviolet (UV) radiation causes excessive cellular oxidative stress, which leads to skin damage, DNA damage, mutations, and skin cancer. This study investigated the protective effects of N-phenethyl caffeamide (K36) from UVA damage on human epidermal keratinocytes. We found that K36 reduced UVA-induced intracellular reactive oxygen species (ROS) production and induced the expression of the intrinsic antioxidant enzyme heme oxygenase-1 (HO-1) by increasing the translocation of nuclear factor erythroid 2(-)related factor 2 (Nrf2). K36 could inhibit the phosphorylation of extracellular-signal-regulated kinase (ERK) and c-Jun N-terminal kinases (JNK) and reduce UVA-induced matrix metalloproteinase (MMP)-1 and MMP-2 overexpression; it could also elevate the expression of tissue inhibitors of metalloproteinases (TIMP). In addition, K36 ameliorated 8-hydroxy-2'-deoxyguanosine (8-OHdG) induced by UVA irradiation. Furthermore, K36 could downregulate the expression of inducible nitric oxide synthase (iNOS) and interleukin-6 (IL-6) and the subsequent production of nitric oxide (NO) and prostaglandin E(2) (PGE(2)). Based on our findings, K36 possessed potent antioxidant, anti-inflammatory, antiphotodamage, and even antiphotocarcinogenesis activities. Thus, K36 has the potential to be used to multifunctional skin care products and drugs. FAU - Chu, Yin AU - Chu Y AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. dooo517@outlook.com. FAU - Wu, Po-Yuan AU - Wu PY AD - Department of Dermatology, China Medical University Hospital, Taichung 40402, Taiwan. wu.poyuan@gmail.com. AD - School of Medicine, China Medical University, Taichung 40402, Taiwan. wu.poyuan@gmail.com. FAU - Chen, Chien-Wen AU - Chen CW AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. walnut0727@hotmail.com. FAU - Lyu, Jia-Ling AU - Lyu JL AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. rain26842006@gmail.com. AD - Ph.D Program for Biotechnology Industry, China Medical University, Taichung 40402, Taiwan. rain26842006@gmail.com. FAU - Liu, Yi-Jung AU - Liu YJ AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. ella8175@gmail.com. AD - Ph.D Program for Biotechnology Industry, China Medical University, Taichung 40402, Taiwan. ella8175@gmail.com. FAU - Wen, Kuo-Ching AU - Wen KC AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. kcwen0520@mail.cmu.edu.tw. FAU - Lin, Chien-Yih AU - Lin CY AD - Department of Biotechnology, Asia University, Taichung 41354, Taiwan. yihlin@asia.edu.tw. FAU - Kuo, Yueh-Hsiung AU - Kuo YH AUID- ORCID: 0000-0001-5935-6755 AD - Department of Biotechnology, Asia University, Taichung 41354, Taiwan. kuoyh@mail.cmu.edu.tw. AD - Department of Chinese Pharmaceutical Sciences and Chinese Medicine Resources, China Medical University, Taichung 40402, Taiwan. kuoyh@mail.cmu.edu.tw. FAU - Chiang, Hsiu-Mei AU - Chiang HM AUID- ORCID: 0000-0002-1586-910X AD - Department of Cosmeceutics, China Medical University, Taichung 40402, Taiwan. hmchiang@mail.cmu.edu.tw. AD - Ph.D Program for Biotechnology Industry, China Medical University, Taichung 40402, Taiwan. hmchiang@mail.cmu.edu.tw. LA - eng GR - CMU105-ASIA-08/China Medical University/ GR - CMU107-BC-7/China Medical University/ GR - MOST 105-2320-B-039-034/the Ministry of Science and Technology/ PT - Journal Article DEP - 20190104 PL - Switzerland TA - Int J Mol Sci JT - International journal of molecular sciences JID - 101092791 RN - 0 (Anti-Inflammatory Agents, Non-Steroidal) RN - 0 (Caffeic Acids) RN - 0 (N-phenethyl caffeamide) RN - 0 (NF-E2-Related Factor 2) RN - 0 (NFE2L2 protein, human) RN - 0 (Reactive Oxygen Species) RN - 31C4KY9ESH (Nitric Oxide) RN - EC 1.14.14.18 (HMOX1 protein, human) RN - EC 1.14.14.18 (Heme Oxygenase-1) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Anti-Inflammatory Agents, Non-Steroidal/*pharmacology MH - Caffeic Acids/*pharmacology MH - Cell Line MH - Cell Survival/drug effects/radiation effects MH - Epidermis/*drug effects/metabolism/radiation effects MH - Heme Oxygenase-1/metabolism MH - Humans MH - Keratinocytes/*drug effects/metabolism/radiation effects MH - Matrix Metalloproteinase 1/metabolism MH - Matrix Metalloproteinase 2/metabolism MH - NF-E2-Related Factor 2/genetics/metabolism MH - Nitric Oxide/antagonists & inhibitors/radiation effects MH - Oxidative Stress MH - Reactive Oxygen Species/metabolism/radiation effects MH - Ultraviolet Rays PMC - PMC6337442 OTO - NOTNLM OT - 8-hydroxy-2'-deoxyguanosine (8-OHdG) OT - N-phenethyl caffeamide OT - heme oxygenase-1 (HO-1) OT - nuclear factor erythroid 2-related factor 2 (Nrf2) OT - photodamage OT - photoinflammation COIS- The authors declare no conflicts of interest. EDAT- 2019/01/10 06:00 MHDA- 2019/04/09 06:00 PMCR- 2019/01/01 CRDT- 2019/01/10 06:00 PHST- 2018/11/22 00:00 [received] PHST- 2018/12/24 00:00 [revised] PHST- 2018/12/27 00:00 [accepted] PHST- 2019/01/10 06:00 [entrez] PHST- 2019/01/10 06:00 [pubmed] PHST- 2019/04/09 06:00 [medline] PHST- 2019/01/01 00:00 [pmc-release] AID - ijms20010164 [pii] AID - ijms-20-00164 [pii] AID - 10.3390/ijms20010164 [doi] PST - epublish SO - Int J Mol Sci. 2019 Jan 4;20(1):164. doi: 10.3390/ijms20010164.