Biliverdin reductase A in the prevention of cellular senescence against oxidative stress

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...

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Bibliographic Details
Published in:Experimental & molecular medicine 2011, 43(1), , pp.15-23
Main Authors: Kim, Sung Young, Kang, Hyun Tae, Choi, Hae Ri, Park, Sang Chul
Format: Article
Language:English
Subjects:
Age Factors
beta-Galactosidase - genetics
beta-Galactosidase - metabolism
Biomedical and Life Sciences
Biomedicine
Blotting, Western
Cell Cycle
Cells, Cultured
Cellular Senescence
Enzyme Induction
Fibroblasts - physiology
G1 Phase
Heme Oxygenase-1 - metabolism
Humans
Hydrogen Peroxide - pharmacology
Medical Biochemistry
Molecular Medicine
Original
Oxidative Stress
Oxidoreductases Acting on CH-CH Group Donors - metabolism
Protein Kinase Inhibitors - metabolism
Reactive Oxygen Species - metabolism
RNA, Small Interfering
Stem Cells
생화학
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Summary: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 (H 2 O 2 ). H 2 O 2 markedly induced BLVRA activity in young HDFs, but not in senescent HDFs. Additionally, depletion of BLVRA reduced the H 2 O 2 -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 RNAitransfected 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 G 0 -G 1 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.
ISSN:1226-3613
2092-6413
DOI:10.3858/emm.2011.43.1.002