Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of inflammation and chronic sepsis on the activity of pyruvate dehydrogenase complex (PDH) in skeletal muscle was investigated in rats. Inflammation was induced by the placement of a catheter in the carotid artery. Sepsis was induced by repeated (every 48 hr) injections of an inoculum composed of Staphylococcus aureus, Escherichia coli, and Bacteroides fragilis organisms into a preformed subcutaneous abscess. Hindlimb muscle was sampled 7 or 14 days following the initial injection of the inoculum into the abscess. Total PHD activity was not altered by any of the conditions examined. There were no differences in the proportion of active PDH complex after 7 days in any of the conditions examined. In contrast, 14 days after the initial bacterial injection, the concentration of active PDH complex in skeletal muscle was reduced by 50% in the septic rats. The combination of intravascular catheterization and infection resulted in a further decrease in the concentration of active PDH complex. The decreased concentration of active PDH complex was associated with increased plasma lactate concentrations in septic rats. Catheterization exacerbated the rise in plasma lactate in sepsis. In this model of chronic sepsis, the magnitude of the hyperlactatemia and the inhibition of the PDH complex in skeletal muscle appear dependent upon the length of time of the septic insult and are potentiated by addition of an intravascular focus of inflammation.
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PMID:Potentiation of decreased pyruvate dehydrogenase activity by inflammatory stimuli in sepsis. 848 21

The ability of cells to sense oxygen is a highly evolved process that facilitates adaptations to the local oxygen environment and is critical to energy homeostasis. In vertebrates, this process is largely controlled by three intracellular prolyl-4-hydroxylases (PHD 1-3). These related enzymes share the ability to hydroxylate the hypoxia-inducible transcription factor (HIF), and therefore control the transcription of genes involved in metabolism and vascular recruitment. However, it is becoming increasingly apparent that proline-4-hydroxylation controls much more than HIF signaling, with PHD3 emerging as an exceptionally unique and functionally diverse PHD isoform. In fact, PHD3-mediated hydroxylation has recently been purported to function in such diverse roles as sympathetic neuronal and muscle development, sepsis, glycolytic metabolism, and cell fate. PHD3 expression is also highly distinct from that of the other PHD enzymes, and varies considerably between different cell types and oxygen concentrations. This review will examine the evolution of oxygen sensing by the HIF-family of PHD enzymes, with a specific focus on complex nature of PHD3 expression and function in mammalian cells.
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PMID:Prolyl-hydroxylase 3: Evolving Roles for an Ancient Signaling Protein. 2467 6