PMID- 37237924
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230530
IS  - 2076-3921 (Print)
IS  - 2076-3921 (Electronic)
IS  - 2076-3921 (Linking)
VI  - 12
IP  - 5
DP  - 2023 May 7
TI  - Metabolic Functions of Biliverdin IXbeta Reductase in Redox-Regulated Hematopoietic 
      Cell Fate.
LID - 10.3390/antiox12051058 [doi]
LID - 1058
AB  - Cytoprotective heme oxygenases derivatize heme to generate carbon monoxide, 
      ferrous iron, and isomeric biliverdins, followed by rapid NAD(P)H-dependent 
      biliverdin reduction to the antioxidant bilirubin. Recent studies have implicated 
      biliverdin IXbeta reductase (BLVRB) in a redox-regulated mechanism of hematopoietic 
      lineage fate restricted to megakaryocyte and erythroid development, a function 
      distinct and non-overlapping from the BLVRA (biliverdin IXalpha reductase) homologue. 
      In this review, we focus on recent progress in BLVRB biochemistry and genetics, 
      highlighting human, murine, and cell-based studies that position BLVRB-regulated 
      redox function (or ROS accumulation) as a developmentally tuned trigger that 
      governs megakaryocyte/erythroid lineage fate arising from hematopoietic stem 
      cells. BLVRB crystallographic and thermodynamic studies have elucidated critical 
      determinants of substrate utilization, redox coupling and cytoprotection, and 
      have established that inhibitors and substrates bind within the single-Rossmann 
      fold. These advances provide unique opportunities for the development of 
      BLVRB-selective redox inhibitors as novel cellular targets that retain potential 
      for therapeutic applicability in hematopoietic (and other) disorders.
FAU - Bahou, Wadie F
AU  - Bahou WF
AUID- ORCID: 0000-0001-6527-8503
AD  - Department of Medicine, School of Medicine, Stony Brook University, Stony Brook, 
      NY 11794, USA.
FAU - Marchenko, Natalia
AU  - Marchenko N
AD  - Department of Pathology, Stony Brook University, Stony Brook, NY 11794, USA.
FAU - Nesbitt, Natasha M
AU  - Nesbitt NM
AUID- ORCID: 0000-0001-5549-0383
AD  - Blood Cell Technologies, 25 Health Sciences Drive, Stony Brook, NY 11790, USA.
LA  - eng
GR  - HL150927/NH/NIH HHS/United States
PT  - Journal Article
PT  - Review
DEP - 20230507
PL  - Switzerland
TA  - Antioxidants (Basel)
JT  - Antioxidants (Basel, Switzerland)
JID - 101668981
PMC - PMC10215512
OTO - NOTNLM
OT  - antioxidant
OT  - cytoprotection
OT  - erythroid development
OT  - megakaryocyte
COIS- N.M.N. is the Chief Scientific Officer of Blood Cell Technologies, which is 
      developing selective BLVRB redox inhibitors for therapeutic applications. The 
      funding agencies had no role in the design of the study; in the collection, 
      analyses, or interpretation of data; in the writing of the manuscript; or in the 
      decision to publish the results.
EDAT- 2023/05/27 09:42
MHDA- 2023/05/27 09:43
PMCR- 2023/05/07
CRDT- 2023/05/27 01:03
PHST- 2023/03/24 00:00 [received]
PHST- 2023/04/19 00:00 [revised]
PHST- 2023/04/27 00:00 [accepted]
PHST- 2023/05/27 09:43 [medline]
PHST- 2023/05/27 09:42 [pubmed]
PHST- 2023/05/27 01:03 [entrez]
PHST- 2023/05/07 00:00 [pmc-release]
AID - antiox12051058 [pii]
AID - antioxidants-12-01058 [pii]
AID - 10.3390/antiox12051058 [doi]
PST - epublish
SO  - Antioxidants (Basel). 2023 May 7;12(5):1058. doi: 10.3390/antiox12051058.