ROS mediated crosstalk between endoplasmic reticulum and mitochondria by Phloxine B under environmental UV irradiation.
Phloxine B (PhB) is a most commonly used dye in cosmetic products throughout the world. It shows an absorption in visible and ultraviolet radiations. PhB was photodegraded within 4h of UV exposure. It generates reactive oxygen species (ROS) photochemically and intracellularly. Photosensitized PhB caused dose dependent cell viability reduction of human keratinocyte cell line (HaCaT) which was measured through MTT (75.4%) and NRU (77.3%) assays. It also induces cell cycle arrest and DNA damage. Photosensitized PhB induces Ca(2+) release from endoplasmic reticulum (ER). It causes the upregulation of ER stress marker genes ATF6 (1.79 fold) and CHOP (1.93 fold) at transcription levels. The similar response of ATF6 (3.6 fold) and CHOP (2.38 fold) proteins was recorded at translation levels. CHOP targeted the mitochondria and reduced the mitochondrial membrane potential analyzed through JC-1 staining. It further increases Bax/Bcl2 ratio (3.58 fold) and promotes the release of cytochrome c, finally leads to caspase-dependent apoptosis. Upregulation of APAF1 (1.79 fold) in PhB treated cells under UV B exposure supports the mitochondrial-mediated apoptotic cell death. The results support the involvement of ER and mitochondria in ROS mediated PhB phototoxicity. Therefore, the use of PhB in cosmetic products may be deleterious to users during sunlight exposure.
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR - IITR, Lucknow 226001, India.
Shruti
S
Goyal
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR - IITR, Lucknow 226001, India; Division of Forensic Science, School of Basic and Applied Science, Galgotias University, Uttar Pradesh, India.
Saroj Kumar
SK
Amar
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
Ajeet Kumar
AK
Srivastav
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
Deepti
D
Chopra
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
Manish Kumar
MK
Pal
Central Instrumentation Facility (TEM), CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India.
Nidhi
N
Arjaria
Photobiology Laboratory, Systems Toxicology and Health Risk Assessment Group, CSIR - Indian Institute of Toxicology Research (CSIR-IITR), M.G. Marg, Lucknow 226001, Uttar Pradesh, India; Academy of Scientific and Innovative Research (AcSIR), CSIR - IITR, Lucknow 226001, India. Electronic address: rsray@iitr.res.in.
Ratan Singh
RS
Ray
D051702:Activating Transcription Factor 6 / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D002118:Calcium / Q000378:metabolism; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D002460:Cell Line; D020552:Comet Assay; D045304:Cytochromes c / Q000378:metabolism; D053903:DNA Breaks, Double-Stranded / Q000187:drug effects / Q000528:radiation effects; D004721:Endoplasmic Reticulum / Q000378:metabolism*; D059865:Endoplasmic Reticulum Stress / Q000528:radiation effects; D010697:Eosine I Bluish / Q000737:chemistry / Q000633:toxicity*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D046529:Microscopy, Electron, Transmission; D008928:Mitochondria / Q000378:metabolism*; D010782:Photolysis / Q000528:radiation effects; D000091402:Prohibitins; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D011740:Pyrimidine Dimers / Q000032:analysis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D051742:Transcription Factor CHOP / Q000378:metabolism; D014466:Ultraviolet Rays; D015854:Up-Regulation / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C497111:ATF6 protein, human; D051702:Activating Transcription Factor 6; C497249:DDIT3 protein, human; C000717328:PHB protein, human; D000091402:Prohibitins; D019253:Proto-Oncogene Proteins c-bcl-2; D011740:Pyrimidine Dimers; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051742:Transcription Factor CHOP; D045304:Cytochromes c; D010697:Eosine I Bluish; D002118:Calcium
Endoplasmic reticulum; Human keratinocyte cell line; Phloxine B; UV R