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

The underlying mechanism of Ca2+ uptake function of cardiac sarcoplasmic reticulum (SR) was investigated in the rat septic shock model produced by cecal ligation and puncture (CLP). The results are as follows. During the early phase of sepsis, the initial rate of ATP-dependent Ca2+ uptake by SR was decreased, while both the capacity of Ca2+ uptake and the activity of Ca(2+)-ATPase were unaffected. In the late sepsis, the impairment in SR function was even greater as the initial rate and the capacity of Ca2+ uptake by SR were significantly decreased, and this was paralleled by a reduction in Ca(2+)-ATPase activity. Although Ca2+ affinity (Km value) to calcium pump and the A0.5 values for Mg2+ and ATP activation on the Ca2+ uptake rate were unchanged, during sepsis the phosphorylation of SR vesicles by adding of catalytic subunit of the cAMP-dependent protein kinase (PKA), calmodulin, or the fragment of PKC into Ca2+ uptake buffer, failed to stimulate Ca2+ uptake activities of SR isolated from early or late septic rats. These data suggest that depression of cardiac SR function is aggravated as sepsis develops, the impairment of SR Ca2+ uptake is possibly based on a mechanism of defective phosphorylation of SR rather than the ionic and energic regulatory actions of Ca2+, Mg2+, ATP on cardiac SR.
 ...
PMID:[Impaired calcium uptake by cardiac sarcoplasmic reticulum and its underlying mechanism during rat septic shock]. 748 74

Myocardial contractile failure is a common cause of morbidity and mortality in patients with ischemic heart disease and inflammatory disorders such as sepsis. Recent research indicates that contractile failure is associated with dysregulation of cytoplasmic calcium levels in the myocyte. However, the specific biochemical alterations responsible for calcium dysregulation remain unclear. In a search for mechanisms which might explain the altered calcium regulation in cardiac cells during ischemia and sepsis, we discovered new roles for an intracellular peptide which regulates intracellular calcium and contractility in myocardial cells. The intracellular peptide carnosine improves contraction in the isolated rat heart and increases free intracellular calcium levels. It stimulates calcium release from the ryanodine calcium-release channel, inhibits calcium uptake by the sarcoplasmic reticulum calcium pump, and sensitizes the contractile proteins to calcium. We believe that this peptide represents a new intracellular messenger system for the regulation/modulation of intracellular calcium. Changes in levels of carnosine may play a role in the altered contractility seen during critical illness.
 ...
PMID:Carnosine: a novel peptide regulator of intracellular calcium and contractility in cardiac muscle. 868 73

Acute respiratory distress syndrome (ARDS) results from overwhelming pulmonary inflammation. Prior bulk RNA sequencing provided limited insights into ARDS pathogenesis. We used single cell RNA sequencing to probe ARDS at a higher resolution. PBMCs of patients with pneumonia and sepsis with early ARDS were compared with those of sepsis patients who did not develop ARDS. Monocyte clusters from ARDS patients revealed multiple distinguishing characteristics in comparison with monocytes from patients without ARDS, including downregulation of SOCS3 expression, accompanied by a proinflammatory signature with upregulation of multiple type I IFN-induced genes, especially in CD16+ cells. To generate an ARDS risk score, we identified upregulation of 29 genes in the monocytes of these patients, and 17 showed a similar profile in cells of patients in independent cohorts. Monocytes had increased expression of RAB11A, known to inhibit neutrophil efferocytosis; ATP2B1, a calcium pump that exports Ca2+ implicated in endothelial barrier disruption; and SPARC, associated with processing of procollagen to collagen. These data show that monocytes of ARDS patients upregulate expression of genes not just restricted to those associated with inflammation. Together, our findings identify molecules that are likely involved in ARDS pathogenesis that may inform biomarker and therapeutic development.
 ...
PMID:Single cell RNA sequencing identifies an early monocyte gene signature in acute respiratory distress syndrome. 3255 32