Absence of mitochondrial superoxide dismutase results in a murine hemolytic anemia responsive to therapy with a catalytic antioxidant.
J Exp Med
; 193(8): 925-34, 2001 Apr 16.
Article
in En
| MEDLINE
| ID: mdl-11304553
Manganese superoxide dismutase 2 (SOD2) is a critical component of the mitochondrial pathway for detoxification of O2(-), and targeted disruption of this locus leads to embryonic or neonatal lethality in mice. To follow the effects of SOD2 deficiency in cells over a longer time course, we created hematopoietic chimeras in which all blood cells are derived from fetal liver stem cells of Sod2 knockout, heterozygous, or wild-type littermates. Stem cells of each genotype efficiently rescued hematopoiesis and allowed long-term survival of lethally irradiated host animals. Peripheral blood analysis of leukocyte populations revealed no differences in reconstitution kinetics of T cells, B cells, or myeloid cells when comparing Sod2(+/+), Sod2(-/-), and Sod2(+/-) fetal liver recipients. However, animals receiving Sod2(-/-) cells were persistently anemic, with findings suggestive of a hemolytic process. Loss of SOD2 in erythroid progenitor cells results in enhanced protein oxidative damage, altered membrane deformation, and reduced survival of red cells. Treatment of anemic animals with Euk-8, a catalytic antioxidant with both SOD and catalase activities, significantly corrected this oxidative stress-induced condition. Such therapy may prove useful in treatment of human disorders such as sideroblastic anemia, which SOD2 deficiency most closely resembles.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Organometallic Compounds
/
Superoxide Dismutase
/
Ethylenediamines
/
Anemia, Hemolytic
/
Mitochondria
/
Antioxidants
Limits:
Animals
Language:
En
Journal:
J Exp Med
Year:
2001
Document type:
Article
Affiliation country:
United States
Country of publication:
United States