Chronic aspartame intake causes deficient glutathione synthesis and induces cxcl1 up-regulation in mice liver

Reduced glutathione (GSH) depletion and inflammation have been linked to chronic aspartame consumption. However, the cause of aspartame-induced GSH depletion and the role of pro- and anti-inflammatory cytokines in aspartame-triggered inflammation are still unknown. The aims of this research were to investigate if aspartame causes GSH depletion due to deficient synthesis and also which pro- and anti-inflammatory genes are involved in aspartame-related inflammation in mice liver. Mice were divided into three groups: control, aspartame (80 mg kg-1, v.o., 3 months), aspartame treated with N-acetylcysteine (NAC) (1 mmol kg-1, i.p., last month). Aspartame markedly reduced GSH, γ-glutamylcysteine …

Time-course of thiol oxidation of protein phosphatases during cerulein-induced acute pancreatitis

Acute pancreatitis (AP) is an acute inflammatory process of the pancreatic gland. The aim of this work was to evaluate the role of thiol oxidation of key proteins that can be involved in the regulation of the inflammatory process during AP. AP was induced in C57BL/6 mice by 7 hourly subcutaneous injections of cerulein (50 ug/kg bw). Animals were sacrificed after 1, 3, 5 and 7 injections of cerulein. One hour after the first injection, hyperoxidation of peroxiredoxin 1–4 was detected coinciding with a H2O2 peak. Three hours later, a marked up-regulation of mRNA and protein expression of sulfiredoxin, partially mediated by Nrf-2, takes place. The up-regulation of sulfiredoxin seems to be resp…

Acute pancreatitis and cystinosis as experimental models of disulfide stress characterized by protein cysteinylation

Disulfide stress is a specific type of oxidative stress that is associated with protein cysteinylation. The aim of this research was to characterize experimental models of disulphide stress. Thus, the redox status of free thiols and protein cysteinylation was studied in acute pancreatitis as an in vivo model of inflammation and in cystinosis an in vitro model of cystine accumulation due to its dysfunctional lysosomal transport. Cystine and homocystine levels, and protein cysteinylation rose after taurocholate-induced acute pancreatitis. Oxidation of cysteines in mitochondrial sulfide quinone oxidoreductase and 60S ribosomal protein L7a was observed. Cysteinylated albumin was also detected. …

Blockade of the trans-sulfuration pathway in acute pancreatitis due to nitration of cystathionine β-synthase

© 2019 Published by Elsevier B.V.

Thioredoxin-related protein of 14 kDa may directly reduce protein cysteinylation motifs

Disulfide stress has been associated with inflammation and characterized by an increase in cystine levels and protein cysteinylation. Furthermore, it was recently discovered that thioredoxin-related protein of 14 kDa (TRP14, encoded by TXNDC17) exhibits efficient cystine reductase activity. The aim of our research was to elucidate if TRP14 is also able to reduce cysteinylated proteins in mammalian cells. Thus, protein cysteinylation was assessed in control and TRP14 knockdown cells in vitro through their pre-treatment with 25 µg/ml cycloheximide for 30 min and incubation with 250 µM biotinylated cysteine for 1 h. Moreover, such TRP14 knockdown cell lysates were tested as cysteinylated subst…

γ-Glutamyl cysteine suppresses TNF-α up-regulation via protein phosphatases in acute pancreatitis

Obesity causes PGC‐1α deficiency in the pancreas leading to marked IL‐6 upregulation via NF‐κB in acute pancreatitis

Obesity is associated with local and systemic complications in acute pancreatitis. PPARγ coactivator 1α (PGC-1α) is a transcriptional coactivator and master regulator of mitochondrial biogenesis that exhibits dysregulation in obese subjects. Our aims were: (1) to study PGC-1α levels in pancreas from lean or obese rats and mice with acute pancreatitis; and (2) to determine the role of PGC-1α in the inflammatory response during acute pancreatitis elucidating the signaling pathways regulated by PGC-1α. Lean and obese Zucker rats and lean and obese C57BL6 mice were used first; subsequently, wild-type and PGC-1α knockout (KO) mice with cerulein-induced pancreatitis were used to assess the inflam…

Nuclear Factor Kappa B Signaling Complexes in Acute Inflammation.

[Significance]: Nuclear factor kappa B (NF-κB) is a master regulator of the inflammatory response and represents a key regulatory node in the complex inflammatory signaling network. In addition, selective NF-κB transcriptional activity on specific target genes occurs through the control of redox-sensitive NF-κB interactions.