title: Implication of microRNA regulation in para-phenylenediamine-induced cell death and senescence in normal human hair dermal papilla cells.
abstract: Para-phenylenediamine (PPD) is a major component of hair coloring and black henna products. Although it has been largely demonstrated that PPD induces allergic reactions and increases the risk of tumors in the kidney, liver, thyroid gland and urinary bladder, the effect on dermal papilla cells remains to be elucidated. Therefore, the current study evaluated the effects of PPD on growth, cell death and senescence using cell-based assays and microRNA (miRNA) microarray in normal human hair dermal papilla cells (nHHDPCs). Cell viability and cell cycle analyses demonstrated that PPD exhibited a significant cytotoxic effect on nHHDPCs through inducing cell death and G2 phase cell cycle arrest in a dose-dependent manner. It was additionally observed that treatment of nHHDPCs with PPD induced cellular senescence by promoting cellular oxidative stress. In addition, the results of the current study indicated that these PPD-mediated effects were involved in the alteration of miRNA expression profiles. Treatment of nHHDPCs with PPD altered the expression levels of 74 miRNAs by ≥ 2-fold (16 upregulated and 58 downregulated miRNAs). Further bioinformatics analysis determined that these identified miRNA target genes were likely to be involved in cell growth, cell cycle arrest, cell death, senescence and the induction of oxidative stress. In conclusion, the observations of the current study suggested that PPD was able to induce several cytotoxic effects through alteration of miRNA expression levels in nHHDPCs.
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Ok-Kyu
authors.initials: OK
authors.lastname: Lee
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Hwa Jun
authors.initials: HJ
authors.lastname: Cha
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Myung Joo
authors.initials: MJ
authors.lastname: Lee
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Kyung Mi
authors.initials: KM
authors.lastname: Lim
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul 143‑729, Republic of Korea.
authors.forename: Jae Wook
authors.initials: JW
authors.lastname: Jung
authors.affiliation: Department of Dermatology, Konkuk University School of Medicine, Seoul 143‑729, Republic of Korea.
authors.forename: Kyu Joong
authors.initials: KJ
authors.lastname: Ahn
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: In-Sook
authors.initials: IS
authors.lastname: An
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Sungkwan
authors.initials: S
authors.lastname: An
authors.affiliation: Korea Institute for Skin and Clinical Sciences and Molecular‑Targeted Drug Research Center, Konkuk University, Seoul 143‑701, Republic of Korea.
authors.forename: Seunghee
authors.initials: S
authors.lastname: Bae
mesh_terms: D059447:Cell Cycle Checkpoints / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000187:drug effects; D003603:Cytotoxins / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D006202:Hair Dyes / Q000633:toxicity*; D018859:Hair Follicle / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D058977:Molecular Sequence Annotation; D018384:Oxidative Stress / Q000187:drug effects; D010655:Phenylenediamines / Q000633:toxicity*; D015398:Signal Transduction
chemical_list: D003603:Cytotoxins; D006202:Hair Dyes; D035683:MicroRNAs; D010655:Phenylenediamines; C029728:4-phenylenediamine