RRC ID 34800
Author Takeda TA, Mu A, Tai TT, Kitajima S, Taketani S.
Title Continuous de novo biosynthesis of haem and its rapid turnover to bilirubin are necessary for cytoprotection against cell damage.
Journal Sci Rep
Abstract It is well known that haem serves as the prosthetic group of various haemoproteins that function in oxygen transport, respiratory chain, and drug metabolism. However, much less is known about the functions of the catabolites of haem in mammalian cells. Haem is enzymatically degraded to iron, carbon monoxide (CO), and biliverdin, which is then converted to bilirubin. Owing to difficulties in measuring bilirubin, however, the generation and transport of this end product remain unclear despite its clinical importance. Here, we used UnaG, the recently identified bilirubin-binding fluorescent protein, to analyse bilirubin production in a variety of human cell lines. We detected a significant amount of bilirubin with many non-blood cell types, which was sensitive to inhibitors of haem metabolism. These results suggest that there is a basal level of haem synthesis and its conversion into bilirubin. Remarkably, substantial changes were observed in the bilirubin generation when cells were exposed to stress insults. Since the stress-induced cell damage was exacerbated by the pharmacological blockade of haem metabolism but was ameliorated by the addition of biliverdin and bilirubin, it is likely that the de novo synthesis of haem and subsequent conversion to bilirubin play indispensable cytoprotective roles against cell damage.
Volume 5
Pages 10488
Published 2015-5-20
DOI 10.1038/srep10488
PII srep10488
PMID 25990790
PMC PMC4438432
MeSH Arsenites / pharmacology Bilirubin / metabolism* Cadmium Chloride / pharmacology Cell Line, Tumor Cytoprotection / physiology* Ferrochelatase / antagonists & inhibitors Ferrochelatase / metabolism Fluorescent Dyes / metabolism HEK293 Cells HeLa Cells Heme / biosynthesis Heme / metabolism* Heme Oxygenase-1 / antagonists & inhibitors Heme Oxygenase-1 / metabolism* Hep G2 Cells Humans MCF-7 Cells Malates / pharmacology Mitochondria / metabolism Oxidoreductases Acting on CH-CH Group Donors / metabolism Protein Binding Sodium Compounds / pharmacology
IF 4.011
Times Cited 10
WOS Category BIOCHEMISTRY & MOLECULAR BIOLOGY
Resource
DNA material pET-His UNAG (RDB13504)