ABSTRACT
The aim of this study was to explore the influence of the neurotoxicity of nanoalumina on primarily cultured neurons. Normal control, particle size control, aluminum, micron-alumina, and nanoalumina at 50-nm and 13-nm particle sizes were included as subjects to evaluate the level of apoptosis, necrosis, and autophagy in primarily cultured neurons and further explore the mitophagy induced by nanoalumina. The results demonstrated that nanoalumina could induce neuronal cell apoptosis, necrosis, and autophagy, among which autophagy was the most notable. When the autophagy inhibitor was added to the nanoalumina-treated group, it significantly downregulated the protein expression levels of Beclin-1 and LC3II/LC3. Observation under a transmission electron microscope and a fluorescence microscope revealed mitophagy characteristics induced by nanoalumina. Additionally, the neurotoxicological effects induced by nanoalumina were more significant than those induced by aluminum and in a particle size-dependent manner.
Subject(s)
Aluminum Oxide , Mitophagy , Aluminum Oxide/metabolism , Aluminum Oxide/toxicity , Animals , Apoptosis , Autophagy , Beclin-1/metabolism , Cells, Cultured , Mitophagy/physiology , Necrosis/metabolism , Neurons , RatsABSTRACT
Aluminum oxide nanoparticles (nano-aluminum) have been known to be widespread in the environment for decades. Exposure to nano-aluminum may impair learning and memory, but the potential mechanism has not yet been elucidated. In neurons, efficient clearance of damaged mitochondria through mitophagy plays an important role in mitochondrial energy supply, neuronal survival, and health. However, abnormal mitophagy induces accumulation of damaged mitochondria, which induces cellular dysfunction, contributing to the impairment of learning and memory. It is currently unclear whether nano-aluminum interferes with the function of nerve cells through mitophagy, leading to learning and memory disorders. Institute of Cancer Research (ICR) female mice were randomly divided into four groups, and treated with normal saline (control) and 50 nm nano-aluminum at concentrations of 25, 50, and 75 mg/kg for 30 days. Our results showed that exposure to nano-aluminum impaired the spatial learning and memory of mice. Superoxide dismutase levels decreased, whereas the levels of malondialdehyde increased. Moreover, there were significant pathological changes in the ultra-structure and function of mitochondria. Finally, expression of autophagy-related proteins LC3-II and Beclin-1 was upregulated and p62 expression decreased, but the expression of apoptotic and necrosis-related proteins had no significant difference among groups. Our results suggest that learning and memory impairment induced by nano-aluminum could be related to mitophagy.
Subject(s)
Aluminum Oxide/toxicity , Memory/drug effects , Mitochondria/pathology , Nanoparticles/toxicity , Spatial Learning/drug effects , Animals , Female , Mice, Inbred ICR , Mitochondria/drug effects , Mitophagy , Oxidative Stress/drug effectsABSTRACT
Dysfunction of the intestinal epithelial barrier plays an important role in the pathogenesis of several intestinal diseases, including celiac disease, inflammatory bowel disease, and irritable bowel syndrome. The present research was carried out to investigate the protective effect of total polysaccharides of adlay bran (TPA) on TNF-α-evoked epithelial barrier dysfunction in Caco-2 cells. Caco-2 cells were treated with or without TPA in the absence or presence of TNF-α, and transepithelial electrical resistance (TEER) and Phenol Red flux were assayed to evaluate the intestinal epithelial barrier function. The results indicated that TPA suppressed the TNF-α-induced release of pro-inflammatory factors. Furthermore, TPA obviously assuaged both the increased paracellular permeability and the decrease of TEER in TNF-α-challenged Caco-2 cells. Furthermore, TPA obviously assuaged TNF-α-evoked up-regulation of IL-8 and IL-6 expression, down-regulation of occludin and ZO-3 expression, and markedly suppressed the activation and protein expression of NF-κB p65. Our results indicated that TPA assuages the TNF-α-evoked dysfunction of the intestinal epithelial barrier by inhibiting the NF-κB p65-mediated inflammatory response.
Subject(s)
Coix/chemistry , Intestinal Mucosa/immunology , Plant Extracts/pharmacology , Polysaccharides/pharmacology , Tumor Necrosis Factor-alpha/immunology , Caco-2 Cells , Epithelial Cells/drug effects , Epithelial Cells/immunology , Humans , Interleukin-6/genetics , Interleukin-6/immunology , Interleukin-8/genetics , Interleukin-8/immunology , Intestinal Mucosa/drug effects , Occludin/genetics , Occludin/immunology , Phosphorylation , Transcription Factor RelA/genetics , Transcription Factor RelA/immunology , Tumor Necrosis Factor-alpha/geneticsABSTRACT
Resveratrol (3,4',5-trihydroxy-trans-stilbene), one of secondary metabolites of low molecular weight present in plant, has various important biological effects. It can induce apoptosis in human leukemia cell types in vitro, although the mechanism is not fully understood. In the present study, we demonstrated reduced viability and DNA synthesis, as well as increased proportion of the subdiploid cell population, in HL-60 cells as determined by cell cycle analysis with resveratrol. Resveratrol treatment resulted in a gradual time-dependent decrease in the expression of anti-apoptotic Bcl-2 and increase in that of Bax, annexin A1, growth arrest- and DNA damage-induced gene 45α (GADD45α), and cleaved caspase-3. In addition, resveratrol markedly increased caspase-3 activity in cells. Our results suggest that resveratrol could inhibit the proliferation and induce apoptosis of HL-60 cells through a GADD45α and annexin A1/caspase-3 pathway.