title: Involvement of cathepsin B in mitochondrial apoptosis by p-phenylenediamine under ambient UV radiation.
abstract: Paraphenylenediamine (PPD), a derivative of paranitroaniline has been most commonly used as an ingredient of oxidative hair dye and permanent tattoos. We have studied the phototoxic potential of PPD under ambient ultraviolet radiation. PPD is photodegraded and form a novel photoproduct under UV A exposure. PPD shows a concentration dependent decrease in cell viability of human Keratinocyte cells (HaCaT) through MTT and NRU test. Significant intracellular ROS generation was measured by DCFDA assay. It caused an oxidative DNA damage via single stranded DNA breaks, micronuclei and CPD formation. Both lysosome and mitochondria is main target for PPD induced apoptosis which was proved through lysosomal destabilization and release of cathepsin B by immunofluorescence, real time PCR and western blot analysis. Cathepsin B process BID to active tBID which induces the release of cytochrome C from mitochondria. Mitochondrial depolarization was reported through transmission electron microscopy. The cathepsin inhibitor reduced the release of cytochrome C in PPD treated cells. Thus study suggests that PPD leads to apoptosis via the involvement of lysosome and mitochondria both under ambient UV radiation. Therefore, photosensitizing nature of hair dye ingredients should be tested before coming to market as a cosmetic product for the safety of human beings.
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
authors.forename: Shruti
authors.initials: S
authors.lastname: Goyal
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
authors.forename: Saroj Kumar
authors.initials: SK
authors.lastname: Amar
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Divya
authors.initials: D
authors.lastname: Dubey
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Manish Kumar
authors.initials: MK
authors.lastname: Pal
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research, CSIR-IITR Campus, Lucknow, India.
authors.forename: Jyoti
authors.initials: J
authors.lastname: Singh
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Ankit
authors.initials: A
authors.lastname: Verma
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
authors.forename: Hari Narayan
authors.initials: HN
authors.lastname: Kushwaha
authors.affiliation: Photobiology Division, CSIR - Indian Institute of Toxicology Research, Post Box No. 80, M.G. Marg, Lucknow 226001, Uttar Pradesh, India. Electronic address: ratanray.2011@rediffmail.com.
authors.forename: Ratan Singh
authors.initials: RS
authors.lastname: Ray
mesh_terms: D000975:Antioxidants / Q000032:analysis / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects*; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000737:chemistry*; D002453:Cell Cycle / Q000187:drug effects; D002460:Cell Line; D004249:DNA Damage; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects / Q000528:radiation effects; D008247:Lysosomes / Q000187:drug effects / Q000528:radiation effects; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D015162:Micronucleus Tests; D008928:Mitochondria / Q000187:drug effects* / Q000528:radiation effects*; D010655:Phenylenediamines / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000032:analysis; D014466:Ultraviolet Rays
chemical_list: D000975:Antioxidants; D010655:Phenylenediamines; D017382:Reactive Oxygen Species; D002401:Cathepsin B; C029728:4-phenylenediamine
keywords: Apoptosis; Cathepsin B; Cytochrome C; PPD (paraphenylenediamine); Phototoxicity