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)

The regulation of tetrapyrrole biosynthesis in higher plants has been attributed to metabolic feedback inhibition of Glu tRNA reductase by heme. Recently, another negative regulator of tetrapyrrole biosynthesis has been discovered, the FLU protein. During an extensive second site screen of mutagenized flu seedlings a suppressor of flu, ulf3, was identified that is allelic to hy1 and encodes a heme oxygenase. Increased levels of heme in the hy1 mutant have been implicated with inhibiting Glu tRNA reductase and suppressing the synthesis of delta-aminolevulinic acid (ALA) and Pchlide accumulation. When combined with hy1 or ulf3 upregulation of ALA synthesis and overaccumulation of protochlorophyllide in the flu mutants were severely suppressed supporting the notion that heme antagonizes the effect of the flu mutation by inhibiting Glu tRNA reductase independently of FLU. The coiled-coil domain at the C-terminal end of Glu tRNA reductase interacts with FLU, whereas the N-terminal site of Glu tRNA reductase that is necessary for the inhibition of the enzyme by heme is not required for this interaction. The interaction with FLU is specific for the Glu tRNA reductase encoded by HEMA1 that is expressed in photosynthetically active tissues. FLU seems to be part of a second regulatory circuit that controls chlorophyll biosynthesis by interacting directly with Glu tRNA reductase not only in etiolated seedlings but also in light-adapted green plants.
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PMID:Concurrent interactions of heme and FLU with Glu tRNA reductase (HEMA1), the target of metabolic feedback inhibition of tetrapyrrole biosynthesis, in dark- and light-grown Arabidopsis plants. 1558 60

Monocytes are composed of two distinct subpopulations in the peripheral blood as determined by their surface antigen expressions, profiles of cytokine production and functional roles played in vivo. We attempted to delineate the unique functional roles played by a minor CD16(high)CCR2(-) subpopulation of circulating monocytes. They produced significant levels of interleukin (IL)-6 and tumour necrosis factor (TNF)-alpha, but very low levels of IL-10 upon in vitro stimulation. Characteristic profiles of cytokine production were confirmed by stimulating purified subpopulations of monocytes after cell sorting. It was noteworthy that freshly isolated CD16(high)CCR2(-) monocyte subpopulations produced significant levels of haem oxygenase (HO)-1, whereas the major CD16(low)CCR2(+) subpopulation produced little. These results were contrary to the generally accepted notion that the CD16(high)CCR2(-) monocyte subpopulation plays a predominantly proinflammatory role in vivo. The CD16(high)CCR2(-) subpopulation increased in Kawasaki disease and influenza virus infection. In accord with this, HO-1 mRNA expression by mononuclear cells was significantly increased in these illnesses. These results indicate that CD16(high)CCR2(-) subpopulations are of a distinct lineage from CD16(low)CCR2(+) monocytes. More importantly, they may represent a monocyte subpopulation with a unique functional role to regulate inflammation by producing HO-1 in steady state in vivo.
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PMID:Selective expansion of CD16highCCR2- subpopulation of circulating monocytes with preferential production of haem oxygenase (HO)-1 in response to acute inflammation. 1629 58

Mortality after influenza is often due to secondary bacterial pneumonia with Streptococcus pneumoniae, particularly in the elderly. The reasons for the high fatality rate seen with this disease are unclear. To further characterize the pathogenesis of pneumonia after influenza in a mouse model, we examined the pathology and immunology that leads to fatal infection. Influenza-infected mice were either euthanized 24 h after secondary infection with S. pneumoniae for determination of pathology, bacterial cultures, and levels of immune effectors or were followed by use of a live imaging system for development of pneumonia. Influenza-infected mice challenged with each of 3 serotypes of pneumococcus developed a severe, necrotic pneumonia and met endpoints for euthanasia in 24 to 60 h. Strikingly elevated levels of both pro- and anti-inflammatory molecules including interleukins 6 and 10, macrophage inflammatory protein 1alpha, and chemokine KC were present in the blood. High levels of these cytokines and chemokines as well as tumor necrosis factor alpha, interleukin 1beta, and heme oxygenase 1 were present in the lungs, accompanied by a massive influx of neutrophils. Mortality correlated with the development of pneumonia and lung inflammation but not with bacteremia. This model has the potential to help us understand the pathogenesis of severe lung infections.
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PMID:Induction of pro- and anti-inflammatory molecules in a mouse model of pneumococcal pneumonia after influenza. 1734 95

Homeostasis of the reduction-oxidation (redox) state is critical to protection from oxidative stress in the lungs. Therefore, the lungs have high levels of antioxidants, including glutathione, heme oxygenase, and superoxide dismutase. The numbers of inflammatory cells -- particularly eosinophils -- are increased in the airways of asthma patients, and these pulmonary inflammatory cells release large amounts of harmful reactive oxygen species and reactive nitrogen species. Human thioredoxin 1 (TRX1) is a redox-active protein of approximately 12 kDa that contains a (32)Cys-Gly-Pro-(35)Cys sequence necessary for its activity. The strong reducing activity of the sequence results from the cysteine residues acting as proton donors and cleaving disulfide (S-S) bonds in the target protein. Endogenous or exogenous TRX1 or both protect the lungs against ischemia-reperfusion injury, influenza infection, bleomycin-induced injury, or lethal pulmonary inflammation caused by interleukin-2 and interleukin-18. We showed that exogenous TRX1 inhibits airway hyperresponsiveness and pulmonary inflammation accompanied by eosinophilia in mouse models of asthma. Recently, we reported that exogenous TRX1 improves established airway remodeling in a prolonged antigen-exposure mouse asthma model. Exogenous and endogenous TRX1 also prevents the development of airway remodeling. Here, we discuss the role and clinical benefits of TRX1 in asthma.
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PMID:Redox-regulated mechanisms in asthma. 1817 61