Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0409974 (lupus)
 22,386 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To test the hypothesis that T-cells which exhibit abnormal immunological behavior manifest derangements in the de novo synthesis of phospholipids, the utilization of [3H]palmitic acid in B220+ T-cells from autoimmune MRL-lpr/lpr mice was investigated. The rate of incorporation of [3H]palmitic acid into membrane phospholipids was markedly increased in intact B220+ T-cells compared to that in T-cells from immunologically normal mice. The activities of two key enzymes involved in the de novo synthesis of palmitoyl-phospholipids, acyl-coenzyme (CoA) ligase and acyl-CoA; sn-glycerol-3-phosphate acyl transferase, were significantly higher in homogenates from B220+ T-cell membranes compared with those in controls. Despite these findings, the molar concentration of individual palmitoyl glycerolipids was equivalent in the membranes of B220+ T-cells and control lymph node T-cells. The results indicate that T-cells from lupus mice exhibit complex defects in the biosynthesis and turnover of membrane phospholipids and suggest the possibility that these aberrations contribute to T-cell dysfunction in autoimmune diseases.
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PMID:Long chain fatty acid utilization of T-cells from autoimmune MRL-lpr/lpr mice. 809 30

To date, the pathogenesis of systemic lupus erythematosus (SLE) remains unclear. By critically analyzing clinical facts and laboratory data, a hypothesis is proposed: drug-induced lupus erythematosus (DILE) is linked to a deficiency in Coenzyme A (CoA) that is secondary to a deficiency in pantothenic acid. This hypothesis is used to explain the high incidence of SLE in females, the role of sex hormones in this disease and the mechanism underlying a flare. The actions of anti-malarials and steroids are also discussed. The protean clinical presentation of SLE is attributed to co-existing deficiencies of dietary factors in addition to pantothenic acid. Contributing factors to these deficiencies may include increased nutritional requirements resulting from gene mutations. Treatment is replacement therapy with doses of pantothenic acid that is hundreds of times higher than that of the Dietary Reference Intake (DRI) and other vitamins. Using this method, 12 SLE females were studied with promising results.
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PMID:Systemic lupus erythematosus: a combined deficiency disease. 1514 49

The 3-Hydroxy-3-methyl-glutaryl coenzyme A (HGM-CoA) reductase inhibitors, or statins, are competitive inhibitors of the rate-limiting enzyme in cholesterol synthesis. Generally, statins have an excellent safety profile. Elevations of liver transaminases and creatine phosphokinase with myalgia have been associated with the use of HGM-Co A reductase inhibitors, case reports of rhabdomyolysis are rare, most occurring with concomitant use with other drugs such as cyclosporin, fusidic acid and gemfibrozil. We describe here the clinical case of a patient who developed interstitial lung disease as probably a result of the use of statins which particularly increased with long-term atorvastatin treatment. The present review details some case-reports of interstitial lung disease reported under statins in the literature. Few systemic adverse effects such as lupus-like-syndromes and polymyositis have been reported. Recent experimentations have demonstrated that cholesterol is not the only intracellular target of statins but that they also have a potential role in atherosclerosis and in organ transplantation as immunosuppressor agents.
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PMID:[A case of interstitial lung disease with atorvastatin (Tahor) and a review of the literature about these effects observed under statins]. 1679 55

Statins, also known as 3-hydroxy-3-methylglutaril-CoA reductase inhibitors, are well-tolerated drugs used for prevention of atherosclerosis and cardiovascular events. Although they are generally considered safe, some serious adverse effects, such as myositis, myopathy, and rhabdomyolysis can rarely occur. Furthermore, recent data from long-term follow-up on patients who have been taking statins for a long period of time suggest that prolonged exposure to statins may trigger autoimmune reactions. The exact mechanism of statin-induced autoimmune reactions is unclear. Statins, as proapoptotic agents, release nuclear antigen into the circulation and may induce the production of pathogenic autoantibodies. Herein we report the case of a 70 year-old man who developed a relapse of pemphigus erythematosus, a syndrome with features of both lupus erythematosus and pemphigus, after atorvastatin intake.
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PMID:Pemphigus erythematosus relapse associated with atorvastatin intake. 2525 14

FcgRIIB dysfunction is commonly found in patients with lupus, especially in Asia. LPS-tolerance is prominent in FcgRIIB-/- lupus mice. LPS-tolerant macrophages demonstrate cell energy depletion, which might affect lipid metabolism. Therefore, to explore lipid metabolism, LPS-tolerance was induced twice by LPS administration in macrophages and in mice. LPS-tolerant FcgRIIB-/- macrophages demonstrated lesser mitochondrial DNA (mtDNA), more severe ATP depletion, lower cytokine production, and higher lipid accumulation (oil red O staining) compared to LPS-tolerant WT cells. Mass-spectrometry-based lipidomic analysis demonstrated a higher abundance of phosphatidylethanolamine (PE) phospholipid in LPS-tolerant FcgRIIB-/- macrophages than WT cells. This was at least in part due to the lower expression of phosphatidylethanolamine N-methyltransferase (pemt), an enzyme that converts PE to phosphatidylcholine (PC). Aminoimidazole-4-carboxamide ribonucleotide (AICAR), a pemt inhibitor, worsens LPS-tolerance in WT macrophages and supports the impact of pemt upon LPS-tolerant FcgRIIB-/- macrophages. Additionally, phosphorylated AMP-activated protein kinase (AMPK-p), a molecule for ATP-restoration associated with pemt, and phosphorylated acetyl CoA carboxylase, a downstream signaling of AMPK-p, were higher in LPS-tolerant FcgRIIB-/- macrophages than WT. Furthermore, Compound C, an AMPK inhibitor, attenuated LPS-tolerance in both FcgRIIB-/- macrophages and mice. Taken together, the intense decrease in cytokine production after the second LPS stimulation (LPS-tolerance) in FcgRIIB-/- macrophages was possibly due to the impact of an immense cytokine synthesis after the first dose of LPS. This includes using up PEMT, an enzyme of phospholipid synthesis during cytokine production, and AMPK-p induction in response to profound ATP-depletion. Therefore, the manipulation of the AMPK/PEMT axis provides a novel therapeutic candidate for the treatment of severe LPS-tolerance in lupus.
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PMID:Dysregulation of Lipid Metabolism in Macrophages Is Responsible for Severe Endotoxin Tolerance in FcgRIIB-Deficient Lupus Mice. 3258 49