title: Green fluorescent protein chromophore derivative suppresses ultraviolet A-induced JNK-signalling and apoptosis in keratinocytes and adverse effects in zebrafish embryos.
abstract: Solar ultraviolet (UV) light has been recognized as the important environmental hazard and contributes to diverse skin damage such as cell death, photoageing and even carcinogenesis. Revelation of harmful responses attributed to UVA radiation has promoted the development of photoprotective agents against UVA-induced skin damage. In the present study, we tried to evaluate the potential protective effects of a synthetic green fluorescent protein (GFP) chromophore derivative, 4-chlorobenzyldene-1, 2-dimethylimidazolinone (Cl-BDI, called TC-22) on UVA- and UVB- induced stress responses in skin. The HaCaT keratinocytes were used to evaluate the cellular effects. Zebrafish (Danio rerio), which is regarded as a useful and cost-effective alternative to some mammalian models, was applied as the in vivo animal model. In HaCaT keratinocytes, TC-22 was able to obviously decrease UVA-induced cell death. Dissection of the UVA-induced signalling pathways revealed that TC-22 could suppress the activation of JNK and caspase 3, but not of ERK and p38. Reduction of UVA-induced cleavage of caspase 3 and sub-G1 phase accumulation by pretreatment of TC-22 was also observed. In zebrafish, we showed that UVA irradiation could decrease the survival and hatching rate, suppress heart beats of embryos and enhance the pigmentation of larvae. Pretreatment of TC-22 could significantly reverse UVA-induced the suppression in hatching of eggs and heart beating of embryos and also lowered the UVA-induced pigmentation in zebrafish. Collectively, we demonstrate that TC-22, a GFP chromophore derivative, can ameliorate the UVA-induced stress responses in both epidermal keratinocytes and zebrafish, suggesting the potential use of TC-22 in photoprotection in the future.
authors: Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.|Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan.|Mackay Junior College of Medicine, Nursing and Management, New Taipei City, Taiwan.
authors: Nan-Lin
authors: NL
authors: Wu
authors: Department of Urology, Hsinchu Mackay Memorial Hospital, Hsinchu, Taiwan.
authors: Te-An
authors: TA
authors: Lee
authors: Graduate Institute of Basic Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Sheng-Fen
authors: SF
authors: Wang
authors: Department of Chemistry, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Hsin-Ju
authors: HJ
authors: Li
authors: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung, Taiwan.
authors: Hui-Ting
authors: HT
authors: Chen
authors: Department of Chemistry, National Taiwan Normal University, Taipei, Taiwan.
authors: Tun-Cheng
authors: TC
authors: Chien
authors: Department of Dermatology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan.
authors: Chieh-Chen
authors: CC
authors: Huang
authors: School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan.
authors: Chi-Feng
authors: CF
authors: Hung
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D002460:Cell Line; D004353:Drug Evaluation, Preclinical; D004625:Embryo, Nonmammalian / Q000187:drug effects / Q000528:radiation effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology / Q000627:therapeutic use*; D015603:Keratinocytes / Q000187:drug effects*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D015595:Skin Aging / Q000187:drug effects*; D013471:Sunburn / Q000517:prevention & control*; D014466:Ultraviolet Rays / Q000009:adverse effects; D015027:Zebrafish
chemical_list: D007093:Imidazoles
keywords: GFP chromophore; keratinocyte; ultraviolet; zebrafish