Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0014070 (encephalomyelitis)
 13,017 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Oxidative stress is implicated in the pathogenesis of experimental allergic encephalomyelitis (EAE), a model for multiple sclerosis. Heme oxygenase-1 (HO-1) is a heat shock protein induced by oxidative stress. HO-1 metabolizes the pro-oxidant heme to the antioxidant biliverdin and CO. HO-1 requires electrons, donated by NADPH cytochrome P450 reductase (henceforth, reductase), for catalytic activity. EAE was induced with a peptide of proteolipid protein in SJL mice, and the expression of HO-1 and reductase in the hindbrain was analyzed. HO-1 protein levels were significantly increased in EAE animals compared with control mice. HO-1 expression was present in ameboid macrophages, reactive microglia, and astrocytes in white matter tracks. Bergmann glia and ameboid macrophages also were occasionally stained in the molecular layer of the cerebellum. Unlike HO-1, reductase protein levels decreased with disease severity. HO-1 and reductase were associated with each other in endoplasmic reticulum micelles, suggesting that the decrease in reductase does not interfere with its association with HO-1. In cells that express HO-1, the association of reductase with HO-1 should competitively inhibit the interaction of reductase with cytochrome P450 isozymes and thereby limit free radical production as the latter two enzymes act cooperatively to produce superoxide. The increase in HO-1 together with the decrease in reductase may be part of a common defense mechanism attempting to minimize tissue damage in several neurological conditions.
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PMID:Heme oxygenase-1 and NADPH cytochrome P450 reductase expression in experimental allergic encephalomyelitis: an expanded view of the stress response. 1108 Feb 9

Baculovirus immediate early P35 protein is well known for its anti-apoptotic as well as anti-oxidant properties. Mechanism of action of P35 involves inhibition of a vast range of initiator to executioner class of caspases. In addition, P35's role in inhibiting oxidant-induced mitochondrial damage, primarily in the apoptotic pathway, has also been extensively investigated. Elucidation of P35's functions during regulation of programmed cell death (PCD) has led to a renewed focus on exploiting this basic knowledge for clinical and other related applications. This review outlines specific biochemical and genetic pathways where P35 intervenes and regulates rate-limiting steps in the apoptotic signaling cascade. Research efforts are underway to utilize P35 as an agent in regulating apoptosis and under certain circumstances, also explore the therapeutic potential of its anti-oxidant features. One of the major outcomes of recent studies include significantly improved effectiveness of cytochrome P450 directed enzyme pro-drug delivery tools when used in conjunction with P35, which may help in alleviating drug resistance in tumor cells and simultaneously prolonging the cytotoxic effects of anti-cancer drugs. Moreover, applied research carried out recently in the fields of diabetes, ischemia-induced neuronal cell death, experimental autoimmune encephalomyelitis (EAE), multiple sclerosis (MS), inflammatory arthritis, cardiovascular and ocular disorders illustrate P35's utilization across diverse therapeutic areas and will certainly make it an attractive biomolecule for the discovery research.
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PMID:Baculovirus P35 protein: an overview of its applications across multiple therapeutic and biotechnological arenas. 1983 Aug 25

The aryl hydrocarbon receptor (AHR), which has been central to studies in toxicology for years as the receptor for the toxicant dioxin, is rapidly gaining interest in immunology based on its ability to influence T-cell differentiation. Multiple studies have documented that binding of this receptor with certain ligands favors T-cell differentiation toward regulatory T cells, and paradoxically, binding of this same receptor with different ligands enhances Th17 effector cell differentiation. This finding has been confirmed in both in vitro and in vivo models, where different ligands are able to either ameliorate or conversely aggravate autoimmunity in experimental autoimmune encephalomyelitis. The AHR has both an endogenous role that is important in development and normal physiology and an exogenous role as a receptor for manmade toxicants, with their binding leading to transcription of cytochrome P450 enzymes that metabolize these same ligands. Based on recent reports that will be summarized in this overview, we will consider the role that the AHR might play as a sensor to the outside environment, leading to alteration of the acquired immune system that might have relevance in transplantation or other medical conditions. In addition to describing the data in normal physiology and T-cell differentiation, we will present examples of the importance of this receptor in preclinical models of disease and highlight specific ligands that target the AHR and will have efficacy in treating transplant rejection and in tolerance protocols.
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PMID:The aryl hydrocarbon receptor: a novel target for immunomodulation in organ transplantation. 2326 8