title: CYB5D2 enhances HeLa cells survival of etoposide-induced cytotoxicity.
abstract: Cytochrome b5 domain containing 2 (CYB5D2) (neuferricin) belongs to the family of membrane-associated progesterone receptors (MAPRs). MAPRs affect multiple cellular processes, including proliferation, differentiation, and survival. Consistent with these observations, we report here that CYB5D2 enhances HeLa cells survival of etoposide (ETOP)-mediated cytotoxicity. Overexpression of CYB5D2 enhanced the survival of HeLa cells compared with HeLa cells transfected with empty vector (EV) upon ETOP treatment. As ETOP initiates ATM-dependent DNA damage response (DDR), we were able to show that CYB5D2 did not affect ETOP-induced DDR. In line with these observations, CYB5D2 did not protect HeLa cells from UV-induced cytotoxicity. Additionally, CYB5D2 had no effects on TNFα-induced apoptosis. Collectively, CYB5D2 enhances HeLa cell survival of ETOP-induced cytotoxicity with some specificity. CYB5D2 contains a cytochrome b5 (cyt-b5) domain and a transmembrane (TM) motif. Both domains are required for CYB5D2-mediated protection of HeLa cells from ETOP-induced cytotoxicity. In an effort to search for the underlying mechanisms, we have profiled gene expression between HeLa-CYB5D2 and HeLa-EV cells. Although ectopic CYB5D2 does not massively alter gene expression, the expression of several transcripts was affected more than 2-fold, suggesting that they may contribute to CYB5D2-mediated HeLa cell survival of ETOP treatment.
authors.affiliation: Division of Nephrology, Department of Medicine, McMaster University, St. Joseph's Hospital, Hamilton, ON, Canada.
authors.forename: Yanyun
authors.initials: Y
authors.lastname: Xie
authors.forename: Anthony
authors.initials: A
authors.lastname: Bruce
authors.forename: Lizhi
authors.initials: L
authors.lastname: He
authors.forename: Fengxiang
authors.initials: F
authors.lastname: Wei
authors.forename: Lijian
authors.initials: L
authors.lastname: Tao
authors.forename: Damu
authors.initials: D
authors.lastname: Tang
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis / Q000187:drug effects* / Q000528:radiation effects; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects / Q000528:radiation effects; D015786:Cytochromes b5 / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D005047:Etoposide / Q000633:toxicity*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D015870:Gene Expression; D020869:Gene Expression Profiling; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D009928:Organ Specificity; D010957:Plasmids; D017434:Protein Structure, Tertiary / Q000235:genetics*; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014466:Ultraviolet Rays
chemical_list: D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D005047:Etoposide; D015786:Cytochromes b5