Liver glycogen metabolism in endotoxin shock

Liu, Maw-Shung; Kang, Ge-Fei

doi:10.1016/0885-4505(87)90011-9

Cited by 6 publications

(2 citation statements)

References 11 publications

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“…Indirect evidence of elevated calcium concentration in sepsis has been obtained by several studies showing increased activities of calcium-dependent proteases in tissues of septic animals, such as calpain [29] and glycogen phosphorylase-b kinase [30]. The immunofluorescence findings in the present study demonstrated an increased expression of calpain-1 in cardiomyocytes submitted to septic serum challenge as compared with that observed in cardiomyocytes tested with control serum.…”

Section: Discussionsupporting

confidence: 68%

Disruption of Calcium Homeostasis in Cardiomyocytes Underlies Cardiac Structural and Functional Changes in Severe Sepsis

et al. 2013

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Sepsis, a major cause of morbidity/mortality in intensive care units worldwide, is commonly associated with cardiac dysfunction, which worsens the prognosis dramatically for patients. Although in recent years the concept of septic cardiomyopathy has evolved, the importance of myocardial structural alterations in sepsis has not been fully explored. This study offers novel and mechanistic data to clarify subcellular events that occur in the pathogenesis of septic cardiomyopathy and myocardial dysfunction in severe sepsis. Cultured neonatal mice cardiomyocytes subjected to serum obtained from mice with severe sepsis presented striking increment of [Ca2+]i and calpain-1 levels associated with decreased expression of dystrophin and disruption and derangement of F-actin filaments and cytoplasmic bleb formation. Severe sepsis induced in mice led to an increased expression of calpain-1 in cardiomyocytes. Moreover, decreased myocardial amounts of dystrophin, sarcomeric actin, and myosin heavy chain were observed in septic hearts associated with depressed cardiac contractile dysfunction and a very low survival rate. Actin and myosin from the sarcomere are first disassembled by calpain and then ubiquitinated and degraded by proteasome or sequestered inside specialized vacuoles called autophagosomes, delivered to the lysosome for degradation forming autophagolysosomes. Verapamil and dantrolene prevented the increase of calpain-1 levels and preserved dystrophin, actin, and myosin loss/reduction as well cardiac contractile dysfunction associated with strikingly improved survival rate. These abnormal parameters emerge as therapeutic targets, which modulation may provide beneficial effects on future vascular outcomes and mortality in sepsis. Further studies are needed to shed light on this mechanism, mainly regarding specific calpain inhibitors.

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Section: Discussionsupporting

confidence: 68%

Disruption of Calcium Homeostasis in Cardiomyocytes Underlies Cardiac Structural and Functional Changes in Severe Sepsis

et al. 2013

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“…The kidneys and liver have been found to participate in the synthesis and accumulation of glycogen during the progression of sepsis [ 29 , 30 ]. Several studies have attributed the alteration of glycogen stores to changes in the activities of glycogen synthase [ 31 , 32 ], and glucose metabolic disorder is mediated by inflammatory cytokines such as IL-1, IL-6, and TNF-α [ 33 ]. These cytokines can have direct effects on hepatocytes or alter the expression levels of glycol-regulatory hormones.…”

Section: Discussionmentioning

confidence: 99%

Whey Acidic Protein/Four-Disulfide Core Domain 21 Regulate Sepsis Pathogenesis in a Mouse Model and a Macrophage Cell Line via the Stat3/Toll-Like Receptor 4 (TLR4) Signaling Pathway

Xie¹,

Guo²,

Liu³

2018

Med Sci Monit

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BackgroundWhey acidic protein/four-disulfide core domain 21 (Wfdc21), also known as Lnc-DC, it has been reported to be correlated with immune response. However, the role of Wfdc21 in the pathogenesis of sepsis is still unknown. In the present study, we aimed to investigate the role of Wfdc21 in the pathogenesis of sepsis.Material/MethodsThe cecal ligation and puncture (CLP)-induced sepsis model was established in Balb/c mice. Animals were euthanized 4, 8, 16, or 24 h after CLP. The glycogen distribution in the kidney and liver was checked by Periodic acid-Schiff (PAS) staining. Changes in the serum interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α) concentrations were monitored with ELISA, and Wdfc21 expression was determined by qPCR. Mouse macrophage-like RAW264.7 cells were treated with different doses of lipopolysaccharide (LPS) from Escherichia coli to mimic sepsis in vitro. Western blot analysis was performed to confirm whether LPS-induced in vitro sepsis was correlated with the involvement of the Stat3/TLR4 signaling pathway. In addition, RAW 264.7 cells were infected with lentiviruses containing Wfdc21 shRNA to further confirm the role of Wfdc21 in the pathogenesis of sepsis.ResultsWe found that Wfdc21 level was elevated in the CLP-induced animal model and LPS-treated RAW264.7 cells. Furthermore, the downregulation of Wfdc21 modulated the concentration of pro-inflammatory factors in LPS-treated macrophages, such as IL-1β and TNF-α, in LPS-treated macrophages. This regulatory effect was mediated through the Stat3/TLR4 signaling pathway, since Wfdc21 can regulate p-Stat3 and TLR4 levels in LPS-treated macrophages.ConclusionsWfdc21 plays a critical role in the pathogenesis of sepsis and may provide a therapeutic target for sepsis treatment.

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The control of hepatic glycogen metabolism in an in vitro model of sepsis

2007

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Culturing hepatocytes with a combination of LPS, TNF-alpha, IL-1beta and IFN-gamma resulted in an inhibition of glucose output from glycogen and prevented the repletion of glycogen in freshly cultured cells. The reduced glycogen mobilisation correlated with the lower cell glycogen content and reduced rate of glycogen synthesis from [U-(14)C]glucose rather than alterations in either total phosphorylase or phosphorylase a activity. There was no change in the percentage of glycogen exported as glucose nor the production of lactate plus pyruvate indicating that redistribution of the Gluc-6-P cannot explain the failure of the liver to export glucose. Although changes in glycogen mobilisation correlated with NO production, inhibition of NO synthase by inclusion of L-NMMA in the culture medium failed to prevent the inhibition of either glycogen accumulation or mobilisation by the proinflammatory cytokines, precluding the involvement of NO in this response. LPS plus cytokine treatment had no effect on total glycogen synthase activity although the activity ratio was lowered, indicative of increased phosphorylation. The inhibition of glycogen synthesis correlated with a fall in the intracellular concentrations of Gluc-6-P and UDP-glucose and in the absence of measured changes in kinase activity, it is suggested that the fall in Gluc-6-P reduces both substrate supply and glycogen synthase phosphatase activity. The fall in Gluc-6-P coincided with a reduction in total glucokinase and hexokinase activity within the cells, but no significant change in either the translocation of glucokinase or glucose-6-phosphatase activity. This demonstrates direct cytokine effects on glycogen metabolism independent of changes in glucoregulatory hormones.

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Liver glycogen metabolism in endotoxin shock

Cited by 6 publications

References 11 publications

Disruption of Calcium Homeostasis in Cardiomyocytes Underlies Cardiac Structural and Functional Changes in Severe Sepsis

Disruption of Calcium Homeostasis in Cardiomyocytes Underlies Cardiac Structural and Functional Changes in Severe Sepsis

Whey Acidic Protein/Four-Disulfide Core Domain 21 Regulate Sepsis Pathogenesis in a Mouse Model and a Macrophage Cell Line via the Stat3/Toll-Like Receptor 4 (TLR4) Signaling Pathway

The control of hepatic glycogen metabolism in an in vitro model of sepsis

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