Ameliorative effect of ursolic acid on ochratoxin A-induced renal cytotoxicity mediated by Lonp1/Aco2/Hsp75.

Ochratoxin A (OTA) is a mycotoxin ubiquitous in feeds and foodstuffs. The water-insoluble pentacyclic triterpene bioactive compound, ursolic acid (UA), is widespread in various cuticular waxes of edible fruits, food materials, and medicinal plants. Although studies have reported that oxidative stress was involved in both the nephrotoxicity of OTA and the renoprotective function of UA, the role of stress-responsive Lon protease 1 (Lonp1) in the renoprotection of UA against OTA is still unknown. In this study, cell viability, reactive oxygen species (ROS) production, and several proteins' expressions of human embryonic kidney 293T (HEK293T) cells in response to UA, OTA, and/or Lonp1 inhibitor CDDO-me treatment were detected to reveal the protective mechanism of UA against OTA-induced renal cytotoxicity. Results indicated that a 2 h-treatment of 1 µM UA could significantly alleviate the ROS production and cell death induced by a 24 h-treatment of 8 µM OTA in HEK293T cells (P < 0.05). Compared with the control, the protein expressions of Lonp1, Aco2 and Hsp75 were significantly inhibited after 8 µM OTA treating for 24 h (P < 0.05), which could be notably reversed by the pre-treatment and post-treatment of 1 µM UA (P < 0.05). The protein expressions of Lonp1, Aco2 and Hsp75 were inhibited by the addition of CDDO-me. The three protein expression trends were similar before and after the addition of CDDO-me. In conclusion, OTA could inhibit the expression of Lonp1, suppressing Aco2 and Hsp75 as a result, thereby activating ROS and inducing cell death in HEK293T cells, which could be alleviated by UA pre-treatment.

Advances in Biodetoxification of Ochratoxin A-A Review of the Past Five Decades.

Ochratoxin A (OTA) is a toxic secondary fungal metabolite that widely takes place in various kinds of foodstuffs and feeds. Human beings and animals are inevitably threatened by OTA as a result. Therefore, it is necessary to adopt various measures to detoxify OTA-contaminated foods and feeds. Biological detoxification methods, with better safety, flavor, nutritional quality, organoleptic properties, availability, and cost-effectiveness, are more promising than physical and chemical detoxification methods. The state-of-the-art research advances of OTA biodetoxification by degradation, adsorption, or enzymes are reviewed in the present paper. Researchers have discovered a good deal of microorganisms that could degrade and/or adsorb OTA, including actinobacteria, bacteria, filamentous fungi, and yeast. The degradation of OTA to non-toxic or less toxic OTα via the hydrolysis of the amide bond is the most important OTA biodegradation mechanism. The most important influence factor of OTA adsorption capacity of microorganisms is cell wall components. A large number of microorganisms with good OTA degradation and/or adsorption ability, as well as some OTA degradation enzymes isolated or cloned from microorganisms and animal pancreas, have great application prospects in food and feed industries.

Lon in maintaining mitochondrial and endoplasmic reticulum homeostasis.

As a vital member of AAA+ (ATPase associated with diverse cellular activities) protein superfamily, Lon, a homo-hexameric ring-shaped protein complex with a serine-lysine catalytic dyad, is highly conserved throughout almost all prokaryotic and eukaryotic organisms. Lon protease (LONP) plays an important role in maintaining mitoproteostasis through selectively recognizing and degrading oxidatively modified mitoproteins within mitochondrial matrix, such as oxidized aconitase, phosphorylated mitochondrial transcription factor A, etc. Furthermore, the up-regulated LONP increased mitochondrial ROS generation to promote cell survival, cell proliferation, epithelial-mesenchymal transition, and cell migration, which was attributed to the up-regulation of NADH:ubiquinone oxidoreductase core subunit S8 via interaction with chaperone Lon under hypoxic or oxidative stress in tumorigenesis. In addition, Lon also participated in protein kinase RNA (PKR)-like endoplasmic reticulum kinase signaling pathway under endoplasmic reticulum (ER) stress. In short, Lon, as a pivotal stress-responsive protein that involved in the crosstalks among mitochondria, ER and nucleus, participated in multifarious important cellular processes crucial for cell survival, such as the mitochondrial protein quality control system, the mitochondrial unfolded protein response, the mtDNA maintenance, and the ER unfolded protein response.