E3 ubiquitin ligase TRIM31 alleviates dopaminergic neurodegeneration by promoting proteasomal degradation of VDAC1 in Parkinson's Disease model.

Mitochondrial dysfunction plays a pivotal role in the pathogenesis of Parkinson's disease (PD). As a mitochondrial governor, voltage-dependent anion channel 1 (VDAC1) is critical for cell survival and death signals and implicated in neurodegenerative diseases. However, the mechanisms of VDAC1 regulation are poorly understood and the role of tripartite motif-containing protein 31 (TRIM31), an E3 ubiquitin ligase which is enriched in mitochondria, in PD remains unclear. In this study, we found that TRIM31-/- mice developed age associated motor defects and dopaminergic (DA) neurodegeneration spontaneously. In addition, TRIM31 was markedly reduced both in nigrostriatal region of PD mice induced by MPTP and in SH-SY5Y cells stimulated by MPP+. TRIM31 deficiency significantly aggravated DA neurotoxicity induced by MPTP. Mechanistically, TRIM31 interacted with VDAC1 and catalyzed the K48-linked polyubiquitination to degrade it through its E3 ubiquitin ligase activity. In conclusion, we demonstrated for the first time that TRIM31 served as an important regulator in DA neuronal homeostasis by facilitating VDAC1 degradation through the ubiquitin-proteasome pathway. Our study identified TRIM31 as a novel potential therapeutic target and pharmaceutical intervention to the interaction between TRIM31 and VDAC1 may provide a promising strategy for PD.

Soybean polysaccharide fermentation products regulate the air-liquid interface in co-cultured Caco-2 cells by increasing short chain fatty acids transport.

Soybean polysaccharides have a large molecular weight and complex structure, which is not conducive to body absorption and exerting their biological activities. After the in vitro hydrolysate digestion of soybean polysaccharides, their interactions with intestinal epithelial cell monolayers during soybean polysaccharide-derived short chain fatty acids (SCFAs) uptake and transport were determined by co-culturing soybean polysaccharide hydrolysate products with Caco-2 cells. Based on prepared soybean polysaccharide hydrolysates, physicochemical indices and hydrolysate components were explored and the interface characteristics between SCFAs and Caco-2 cells were characterized using interfacial rheology methods for the first time. Transwell chambers were used to explore relationships between SCFAs transport and the air-liquid interface in Caco-2 cells. We showed that physicochemical properties, cell proliferation rates, and the interfacial tension of soybean polysaccharide hydrolysis products were related to fermentation times, with differences observed between the two hydrolyzed soybean polysaccharides (microwave ammonium oxalate soy hull polysaccharides (MASP) and soluble soy polysaccharides (SSP)). MASP outperformed SSP in terms of total sugar utilization and added cellular value by intestinal flora. Hydrolyzed soybean polysaccharides decreased interfacial tension with increasing hydrolysis times when modulating the interfacial properties of a Caco-2 cell co-culture system. SCFAs translocation rates increased with fermentation time, from 0 h to 24 h. Also, a negative correlation was observed between SCFAs translocation rates and interfacial tension. Our data provide a foundation for the intestinal absorption of soybean polysaccharides and at the same time bring new insights into the interactions between polysaccharides and food in the future, promoting the application of polysaccharides in food processing and even medicine.