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Augmented NRF 2 activation protects adult sickle mice from lethal acute chest syndrome
Author(s) -
Ghosh Samit,
Hazra Rimi,
Ihunnah Chibueze A.,
Weidert Frances,
Flage Bethany,
OforiAcquah Solomon F.
Publication year - 2018
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.15401
Subject(s) - acute chest syndrome , medicine , activator (genetics) , immunology , gastroenterology , sickle cell anemia , disease , receptor
Summary Acute chest syndrome ( ACS ) mortality in sickle cell disease ( SCD ) rises sharply in young adult patients and mechanism‐based prophylaxis is lacking. In SCD , haem oxygenase‐1 ( HO ‐1) declines with age and ACS is associated with low HO ‐1. To test if enhanced HO ‐1 can reduce ACS mortality, young SCD mice were treated with D3T (3H‐1,2‐dithiole‐3‐thione), an activator of nuclear‐factor erythroid 2 like 2, which controls HO ‐1 expression, for 3 months. Following haem‐induced ACS , all vehicle‐treated mice succumbed to severe lung injury, while D3T‐treated mice had significantly improved survival. Blocking HO ‐1 activity abrogated the D3T effect. Thus HO ‐1 may be targeted to reduce ACS severity in adult patients.