Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P04040 (Catalase)
 3,577 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Arsenic trioxide (As2O3) is currently employed as a treatment for relapsed acute promyelocytic leukemia (APL), where it can induce remission in greater than 90% of patients, but is ineffective in patients with non-APL acute myeloid leukemia (AML). As2O3 induces apoptosis in APL cells through mechanisms dependent and independent of the PML-RARalpha fusion protein. Through PML-RARalpha fusion-independent mechanisms, As2O3 increases H2O2 production via its effects on glutathione and glutathione peroxidase. Catalase is an alternative mechanism to convert H2O2 to water. Therefore, we explored the relationship between catalase activity and As2O3 sensitivity. In AML and APL cell lines, but not primary patient samples, basal catalase levels matched sensitivity to As2O3. However, the chemical inhibition of catalase did not enhance As2O3-induced cell death. Failure of catalase inhibition to sensitise cells to As2O3 was due to a failure of catalase inhibition to increased levels of reactive oxygen species. Therefore, other strategies should be explored to enhance the cytotoxicity of As2O3 in AML.
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PMID:Catalase activity and arsenic sensitivity in acute leukemia. 1894 20

MicroRNAs (miRNAs) are emerging as critical regulators of normal and malignant hematopoiesis. In previous studies of acute myeloid leukemia miR-9 overexpression was commonly observed. Here, we show that ectopic expression of miR-9 in vitro and in vivo significantly blocks differentiation of erythroid progenitor cells with an increase in reactive oxygen species (ROS) production. Consistent with this observation, ROS scavenging enzymes, including superoxide dismutase (Sod2), Catalase (Cat), and glutathine peroxidase (Gpx1), are down-regulated by miR-9. In addition, miR-9 suppresses expression of the erythroid transcriptional regulator FoxO3, and its down-stream targets Btg1 and Cited 2 in erythroid progenitor cells, while expression of a constitutively active form of FoxO3 (FoxO3-3A) reverses miR-9-induced suppression of erythroid differentiation, and inhibits miR-9-induced ROS production. Thus, our findings indicate that aberrant expression of miR-9 blocks erythropoiesis by deregulating FoxO3-mediated pathways, which may contribute to the ineffective erythropoiesis observed in patients with hematological malignancies.
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PMID:miR-9 upregulation leads to inhibition of erythropoiesis by repressing FoxO3. 2969 25