title: Cyclophilin 40 alters UVA-induced apoptosis and mitochondrial ROS generation in keratinocytes.
abstract: The CyP40 protein encoded by PPID gene is a member of the peptidyl-prolyl cis-trans isomerase (PPIase) family. PPIases catalyze the cis-trans isomerization of proline imidic peptide bonds in oligopeptides and accelerate the folding of proteins. The CyP40 protein has been shown to possess PPIase activity and, similar to other family members, can bind to the immunosuppressant drug cyclosporin A (CsA). In this study, we created keratinocyte cell lines with CyP40 being stably knocked down using viral particles containing shRNA for CyP40 which knocked down the expression level of CyP40 transcripts by 90-99%. The proliferation rates of the cell lines with silenced CyP40 were decreased compared to the control cells. After UVA irradiation, the rate of apoptosis was found to be significantly lower in CyP40 silenced cell lines than it was in control cells. Moreover, mitochondrial membrane potential (MMP) was found to be less dissipated and mitochondrial permeability transition pore (MPTP) less active in cells with knocked down CyP40 than in control cells after UVA irradiation. Also, less mitochondrial superoxide was detected in the cells with silenced CyP40 compared to control cells after UVA exposure. Moreover, silencing of CyP40 partially modulates expression of key genes involved in mitochondrial pore formation including CyPD, ANTs and VDAC family members. The ability of CyP40 to regulate UV induced apoptosis implicates this protein as a potential target for therapy in cancer cells.
authors.affiliation: Southern Arizona VA Healthcare System and the Department of Medicine, Division of Dermatology and Arizona Cancer Center, University of Arizona, 1515N Campbell Avenue, Tucson, AZ, USA. jjandova@azcc.arizona.edu
authors.forename: Jana
authors.initials: J
authors.lastname: Jandova
authors.forename: Jaroslav
authors.initials: J
authors.lastname: Janda
authors.forename: James E
authors.initials: JE
authors.lastname: Sligh
mesh_terms: D017209:Apoptosis / Q000528:radiation effects*; D015153:Blotting, Western; D049109:Cell Proliferation / Q000528:radiation effects; D002478:Cells, Cultured; D000081406:Peptidyl-Prolyl Isomerase F; D021983:Cyclophilins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology* / Q000528:radiation effects; D008928:Mitochondria / Q000378:metabolism* / Q000528:radiation effects; D033681:Mitochondrial Membrane Transport Proteins / Q000378:metabolism* / Q000528:radiation effects; D000083162:Mitochondrial Permeability Transition Pore; D012333:RNA, Messenger / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014466:Ultraviolet Rays / Q000009:adverse effects*
chemical_list: D000081406:Peptidyl-Prolyl Isomerase F; D033681:Mitochondrial Membrane Transport Proteins; D000083162:Mitochondrial Permeability Transition Pore; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D021983:Cyclophilins