ABSTRACT
Acrylamide (ACR) is present in high-temperature-processed high-carbohydrate foods, cigarette smoke, and industrial pollution. Chronic exposure to ACR may induce neurotoxicity from reactive oxygen species (ROS); however, the mechanisms underlying ACR-induced neurotoxicity remain unclear. We studied 28-day subacute ACR toxicity by repeatedly feeding ACR (0, 15, or 30 mg/kg) to rats. We conducted RNA sequencing and Western blot analyses to identify differences in mRNA expression in the blood and in protein expression in the brain tissues, respectively, of the rats. AQP4 transient transfection was performed to identify potential associations with protein regulation. The rats treated with 30 mg/kg ACR exhibited hind-limb muscle weakness. Matrix metalloproteinase (MMP9) expression was higher in the ACR-treated group than in the control group. ACR induced MMP-9 and AQP4 protein expression in the brain tissues of the rats, which subsequently presented with neurotoxicity. In the in vitro study, Neuro-2a cells were transiently transfected with AQP4, which inhibited MMP-9 and TNF receptor-associated factor 6 (TRAF6) expression, and inhibited ACR induced expression of TRAF6, IκBα, and nuclear factor κB (NFκB). Using a combination of in vivo and in vitro experiments, this study revealed that depressive symptoms associated with ACR-induced neurotoxicity are associated with downregulation of AQP4 and induction of the TRAF6 pathway.
Subject(s)
Acrylamide/toxicity , Aquaporin 4/metabolism , NF-kappa B/antagonists & inhibitors , Neuroprotective Agents/pharmacology , Neurotoxicity Syndromes/prevention & control , TNF Receptor-Associated Factor 6/antagonists & inhibitors , Animals , Aquaporin 4/genetics , Male , Neurotoxicity Syndromes/etiology , Neurotoxicity Syndromes/metabolism , Neurotoxicity Syndromes/pathology , Rats , Rats, Sprague-Dawley , Reactive Oxygen Species/metabolismABSTRACT
A novel lactic acid bacterium, strain MB7T, was isolated from lychee in Taiwan. MB7T is Gram-staining-positive, catalase-negative, non-motile, non-haemolytic, facultatively anaerobic, coccoid-shaped, heterofermentative and mainly produces d-lactic acid from glucose. Comparative analysis of 16S rRNA, pheS and rpoA gene sequences has demonstrated that the novel strain represented a member of the genus Leuconostoc. 16S rRNA gene sequencing results indicated that MB7T had the same sequence similarity of 99.25 % to four type strains of members of the genus Leuconostoc: Leuconostoc mesenteroides subsp. dextranicum DSM 20484T, Leuconostoc mesenteroides subsp. jonggajibkimchii DRC 1506T, Leuconostoc mesenteroides subsp. mesenteroides ATCC 8293T and Leuconostoc suionicum DSM 20241T. Additionally, high 16S rRNA sequence similarities were also observed with Leuconostoc mesenteroides subsp. cremoris ATCC 19254T (99.12 %) and Leuconostoc pseudomesenteroides NRIC 1777T (98.69 %). When comparing the genomes of these type strains, the average nucleotide identity values and digital DNA-DNA hybridization values of MB7T with these type strains were 76.57-80.53 and 22.0-22.6â%, respectively. MB7T also showed different phenotypic characteristics to other most closely related species of the genus Leuconostoc, such as carbohydrate metabolizing ability, halotolerance and growth at various pHs. On the basis of phenotypic and genotypic properties, strain MB7T represents a novel species belonging to the genus Leuconostoc, for which the name Leuconostoc litchii sp. nov. is proposed. The type strain is MB7T (=BCRC 81077T=NBRC 113542T).