title: Biliverdin reductase A in the prevention of cellular senescence against oxidative stress.
abstract: Biliverdin reductase A (BLVRA), an enzyme that converts biliverdin to bilirubin, has recently emerged as a key regulator of the cellular redox cycle. However, the role of BLVRA in the aging process remains unclear. To study the role of BLVRA in the aging process, we compared the stress responses of young and senescent human diploid fibroblasts (HDFs) to the reactive oxygen species (ROS) inducer, hydrogen peroxide (H2O2). H2O2 markedly induced BLVRA activity in young HDFs, but not in senescent HDFs. Additionally, depletion of BLVRA reduced the H2O2-dependent induction of heme oxygenase-1 (HO-1) in young HDFs, but not in senescent cells, suggesting an aging-dependent differential modulation of responses to oxidative stress. The role of BLVRA in the regulation of cellular senescence was confirmed when lentiviral RNAi- transfected stable primary HDFs with reduced BLVRA expression showed upregulation of the CDK inhibitor family members p16, p53, and p21, followed by cell cycle arrest in G0-G1 phase with high expression of senescence-associated β-galactosidase. Taken together, these data support the notion that BLVRA contributes significantly to modulation of the aging process by adjusting the cellular oxidative status.
authors.affiliation: Department of Biochemistry and Molecular Biology, Aging and Apoptosis Research Center, Institute on Aging, Seoul National University College of Medicine, Seoul, Korea.
authors.forename: Sung Young
authors.initials: SY
authors.lastname: Kim
authors.forename: Hyun Tae
authors.initials: HT
authors.lastname: Kang
authors.forename: Hae Ri
authors.initials: HR
authors.lastname: Choi
authors.forename: Sang Chul
authors.initials: SC
authors.lastname: Park
mesh_terms: D000367:Age Factors; D015153:Blotting, Western; D002453:Cell Cycle; D002478:Cells, Cultured; D016922:Cellular Senescence; D004790:Enzyme Induction; D005347:Fibroblasts / Q000502:physiology; D016193:G1 Phase; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D018384:Oxidative Stress; D044925:Oxidoreductases Acting on CH-CH Group Donors / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000378:metabolism; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species / Q000378:metabolism; D001616:beta-Galactosidase / Q000235:genetics / Q000378:metabolism
chemical_list: D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D051547:Heme Oxygenase-1; D044925:Oxidoreductases Acting on CH-CH Group Donors; C019789:biliverdin reductase; D001616:beta-Galactosidase