Patulin induces pro-survival functions via autophagy inhibition and p62 accumulation

Patulin (PAT) is one of the most common mycotoxins found in moldy fruits. Skin contact is one of the most likely exposure routes of PAT. Investigation of dermal toxicity of PAT is clearly needed and has been highlighted by WHO. In the present study, using human keratinocyte HaCaT cells as a model, we found that treatment with PAT caused an increased autophagosome accumulation. Measurements of autophagic flux demonstrated that the accumulation of autophagosomes by PAT was not directly due to enhanced autophagosome formation but due to inhibition of autophagosome degradation. Reductions in the activities of the lysosomal enzymes cathepsin B and cathepsin D by PAT might contribute to this inhibitory effect. Consistent with this, inhibition of autophagosome degradation by PAT resulted in accumulation of p62 that functioned as a pro-survival signal. The pro-survival function of p62 was found to be attributed to reactive oxygen species-mediated cytoprotective endoplasmic reticulum (ER) stress response. ER stress exerted cytoprotective effect via extracellular signal-regulated kinase1/2-dependent B-cell CLL/lymphoma 2-associated agonist of cell death inhibitory phosphorylation. Given the critical role of autophagy and its substrate p62 in carcinogenesis, our findings may have important implications in PAT-induced skin carcinogenesis.     

A Conserved Role for Atlastin GTPases in Regulating Lipid Droplet Size

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Chromosomal Instability Triggered by Rrm2b Loss Leads to IL-6 Secretion and Plasmacytic Neoplasms

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Effects of dietary L-carnitine and coenzyme Q10 supplementation on performance and ascites mortality of broilers

The study was conducted to determine the effects of dietary L-carnitine and coenzyme Q₁₀ (CoQ₁₀) supplementation on growth performance and ascites mortality of broilers. A 3 × 3 factorial arrangement was employed with three levels (0, 75 and 150 mg/kg) of L-carnitine and three levels of CoQ₁₀ (0, 20 and 40 mg/kg) supplementation during the experiment. Five hundred and forty one-day-old Arbor Acre male broiler chicks were randomly allocated into nine groups with six replicates each. All birds were fed with the basal diets from day 1 to 7 and changed to the experimental diets from day 8. During day 15 to 21 all the birds were exposed to low ambient temperature (15 - 18°C) to induce ascites. The results showed that under this condition, growth performance of broilers were not significantly affected by CoQ₁₀ or L-carnitine + CoQ₁₀ supplementation during week 0 - 3 and 0 - 6, but body weight gain (BWG) of broilers was significantly reduced by 150 mg/kg L-carnitine during week 0 - 6. Packed cell volume (PCV) of broilers was significantly decreased by L-carnitine and L-carnitine + CoQ₁₀ supplementation (P < 0.05). Erythrocyte osmotic fragility (EOF), ascites heart index (AHI) and ascites mortality of broilers were significantly decreased by L-carnitine, CoQ₁₀ and L-carnitine + CoQ₁₀ supplementation. Though no significant changes were observed in total antioxidative capability (T-AOC), total superoxide dismutase (T-SOD) was increased by L-carnitine, CoQ₁₀ and L-carnitine + CoQ₁₀ supplementation (P < 0.05). Malonaldehyde (MDA) content was significantly decreased by CoQ₁₀ and L-carnitine + CoQ₁₀ supplementation. The results indicate that dietary L-carnitine and CoQ₁₀ supplementation reduce ascites mortality of broilers; the reason may be partially associated with their antioxidative effects.