Biochimica et biophysica acta
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Biochim. Biophys. Acta · Aug 2013
Metabolic signatures of esophageal cancer: NMR-based metabolomics and UHPLC-based focused metabolomics of blood serum.
Focused metabolic profiling is a powerful tool for the determination of biomarkers. Here, a more global proton nuclear magnetic resonance ((1)H NMR)-based metabolomic approach coupled with a relative simple ultra high performance liquid chromatography (UHPLC)-based focused metabolomic approach was developed and compared to characterize the systemic metabolic disturbances underlying esophageal cancer (EC) and identify possible early biomarkers for clinical prognosis. Serum metabolic profiling of patients with EC (n=25) and healthy controls (n=25) was performed by using both (1)H NMR and UHPLC, and metabolite identification was achieved by multivariate statistical analysis. ⋯ A total of nineteen significantly altered metabolites were identified as the potential disease associated biomarkers. Significant changes in lipid metabolism, amino acid metabolism, glycolysis, ketogenesis, tricarboxylic acid (TCA) cycle and energy metabolism were observed in EC patients compared with the healthy controls. These results demonstrated that metabolic profiling of serum could be useful as a screening tool for early EC diagnosis and prognosis, and might enhance our understanding of the mechanisms involved in the tumor progression.
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Biochim. Biophys. Acta · Aug 2013
Regulation of skeletal muscle oxidative phenotype by classical NF-κB signalling.
Impairments in skeletal muscle oxidative phenotype (OXPHEN) have been linked to the development of insulin resistance, metabolic inflexibility and progression of the metabolic syndrome and have been associated with progressive disability in diseases associated with chronic systemic inflammation. We previously showed that the inflammatory cytokine tumour necrosis factor-α (TNF-α) directly impairs muscle OXPHEN but underlying molecular mechanisms remained unknown. Interestingly, the inflammatory signalling pathway classical nuclear factor-κB (NF-κB) is activated in muscle in abovementioned disorders. Therefore, we hypothesised that muscle activation of classical NF-κB signalling is sufficient and required for inflammation-induced impairment of muscle OXPHEN. ⋯ Classical NF-κB activation impairs skeletal muscle OXPHEN.
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Biochim. Biophys. Acta · Aug 2013
Intermittent-hypoxia induced autophagy attenuates contractile dysfunction and myocardial injury in rat heart.
Sleep apnea syndrome (SAS) is considered to be associated with heart failure (HF). It is known that autophagy is induced in various heart diseases thereby promotes survival, but its excess may be maladaptive. Intermittent hypoxia (IH) plays pivotal role in the pathogenesis of SAS. ⋯ IH-mediated autophagy maintains contractile function, whereas when autophagy is inhibited, IH induces systolic dysfunction due to myocyte necrosis. General significance. This study highlighted the potential implications of autophagy in cardio-protection in early SAS patients without comorbidity, reproduced in normal rats by 3~4weeks of IH.
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Biochim. Biophys. Acta · Jul 2013
Mechanism of capsaicin receptor TRPV1-mediated toxicity in pain-sensing neurons focusing on the effects of Na(+)/Ca(2+) fluxes and the Ca(2+)-binding protein calretinin.
Transient receptor potential vanilloid subtype 1 (TRPV1) receptor is a pain-sensing, ligand-gated, non-selective cation channel expressed in peripheral sensory neurons. Prolonged activation of TRPV1 by capsaicin leads to cell swelling and formation of membrane blebs in rat dorsal root ganglion (DRG) neurons. Similar results were obtained in NIH3T3 fibroblast cells stably expressing TRPV1. ⋯ Swelling and formation of membrane blebs resulted in impaired plasma membrane integrity finally leading to cell death. Our results hint towards a mechanistic explanation for the apoptosis-independent capsaicin-evoked neuronal loss and additionally reveal a protective effect of calretinin; we propose that the Ca(2+)-buffering capacity of calretinin reduces the susceptibility of calretinin-expressing DRG neurons against cell swelling/death caused by overstimulation of TRPV1 channels. This article is part of a Special Issue entitled:12th European Symposium on Calcium.
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Biochim. Biophys. Acta · Jul 2013
ReviewMechanisms of conotoxin inhibition of N-type (Ca(v)2.2) calcium channels.
N-type (Ca(v)2.2) voltage-gated calcium channels (VGCC) transduce electrical activity into other cellular functions, regulate calcium homeostasis and play a major role in processing pain information. Although the distribution and function of these channels vary widely among different classes of neurons, they are predominantly expressed in nerve terminals, where they control neurotransmitter release. To date, genetic and pharmacological studies have identified that high-threshold, N-type VGCCs are important for pain sensation in disease models. ⋯ Surprisingly, however, α-conotoxins Vc1.1 and RgIA, also potently inhibit N-type VGCC currents in the sensory DRG neurons of rodents and α9 nAChR knockout mice, via intracellular signaling mediated by G protein-coupled GABAB receptors. Understanding how conotoxins inhibit VGCCs is critical for developing these peptides into analgesics and may result in better pain management. This article is part of a Special Issue entitled: Calcium channels.