Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:1.14.99.3 (heme oxygenase)
 4,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Alpha-lipoic acid (ALA) is a natural antioxidant that scavenges reactive oxygen species (ROS) and regenerates or recycles endogenous antioxidants. ALA has recently been reported to protect against oxidative injury in various disease processes. The aim of this study was to investigate whether the antioxidant effect of ALA is mediated by the induction of heme oxygenase (HO)-1 in rat aortic smooth muscle cells (A10 cells). ALA significantly induced HO-1 expression accompanied by an increase in HO activity in A10 cells. Pretreatment with ALA increased the resistance of A10 cells to hydrogen-peroxide-induced oxidant stress. This protection of ALA was abrogated in the presence of the HO inhibitor zinc protoporphyrin IX. ALA significantly increased ROS, and this effect was blocked by N-acetyl-cysteine, which also inhibited ALA-induced activation of p44/42 mitogen-activated protein kinase (MAPK) and AP-1, HO-1 expression, and HO activity. These results suggest that ALA induces HO-1 expression through the production of ROS and subsequent activation of the p44/42 MAPK pathway and AP-1 in vascular smooth muscle cells. This study demonstrated that ALA increases the expression of HO-1, a critical cytoprotective molecule, and identified a novel pleiotropic effect of ALA on cardiovascular protection.
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PMID:Heme oxygenase-1 contributes to the cytoprotection of alpha-lipoic acid via activation of p44/42 mitogen-activated protein kinase in vascular smooth muscle cells. 1663 21

The complement cascade (ComC) cleavage fragments C3a and C5a regulate the trafficking of normal, differentiated hematopoietic cells, although they do not chemoattract more primitive hematopoietic stem/progenitor cells (HSPCs). By contrast, human myeloid and lymphoid leukemia cell lines and clonogenic blasts from chronic myelogenous leukemia (CML) and acute myelogenous leukemia (AML) patients respond to C3 and C5 cleavage fragments by chemotaxis and increased adhesion. Consistent with this finding, C3a and C5a receptors are expressed by leukemic cells at the mRNA (RT-PCR) and protein (FACS) levels, and these cells respond to C3a and C5a stimulation by phosphorylation of p44/42 MAPK and AKT. However, neither of these ComC cleavage fragments have an effect on cell proliferation or survival. In parallel, we found that inducible heme oxygenase 1 (HO-1)-an anti-inflammatory enzyme, is a negative regulator of ComC-mediated trafficking of malignant cells and that stimulation of these cells by C3 or C5 cleavage fragments downregulates HO-1 expression in a p38 MAPK-dependent manner, rendering cells exposed to C3a or C5a more mobile. We propose that, while the ComC is not directly involved in the proliferation of malignant hematopoietic cells, its activation in leukemia/lymphoma patients (e.g., as a result of accompanying infections or sterile inflammation after radio-chemotherapy) enhances the motility of malignant cells and contributes to their dissemination in a p38 MAPK-HO-1 axis-dependent manner. Based on this idea, we propose that inhibition of p38 MAPK or upregulation of HO-1 by available small-molecule modulators would have a beneficial effect on ameliorating expansion and dissemination of leukemia/lymphoma cells in clinical situations in which the ComC becomes activated. Finally, since we detected expression of C3 and C5 mRNA in human leukemic cell lines, further study of the potential role of the complosome in regulating the behavior of these cells is needed.
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PMID:The Complement Cascade as a Mediator of Human Malignant Hematopoietic Cell Trafficking. 3123 94