Peroxisome proliferators-activated receptors gamma (PPARγ) is an isoform of PPARs which are members of the nuclear receptor superfamily and are considered as key sensors of lipid and glucose homeostasis. This ligand-activated transcription factor has been intensively studied for more than a decade and the bona fide endogenous ligand remains unknown. 15-Deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2) is of great interest because it affects gene transcription by binding and activating PPARγ and by covalent addition to transcription factors and signaling molecules. However, the actual concentration of 15d-PGJ2 is several orders of magnitude below the levels required to induce many of the biological reaction attributed to this molecule. This short review will focus on 15d-PGJ2 as a ligand of PPARγ and on other candidates of the endogenous ligand for the receptor.
Thioredoxin is a vital component of the thioredoxin system, maintaining the cellular redox environment and regulating various cellular functions. Studies using thioredoxin transgenic mice showed that thioredoxin is protective against diseases associated with oxidative stress. While thioredoxin expression is ubiquitous and constitutive, we observe the induction in some tissues under stress such as ultraviolet irradiation and reperfusion injury. Nerve growth factor (NGF)-, or heme-induced induction of the thioredoxin gene is regulated through cyclic AMP responsive element (CRE) or the antioxidant responsive element (ARE), respectively. Based on these previous studies, we have performed a screening of extracts from vegetables to identify novel thioredoxin inducers. We showed that sulforaphane and extracts from several kinds of vegetables induce marked activation of the thioredoxin gene through ARE and increase the thioredoxin protein level in K562 erythroleukemia cells and retinal pigment epithelial (RPE) cells. Pretreatment with sulforaphane or the extracts from sprouts of red cabbage reduced cellular damage induced by hydrogen peroxide. We also report the effect of sulforaphane on the photooxidative damage of RPE cells. Thioredoxin inducers and thioredoxin have a cytoprotective role against oxidative stress in gastric mucosal cells. Reduction of disulfide bonds in food allergens was reported to facilitate the cleavage by digestive enzymes. These results provide a basis for developing thioredoxin-inducing and containing functional foods and further investigating thioredoxin inducers beneficial for protection against oxidative stress.
The protective effect of squalene on membrane function and mineral status was examined in isoproterenol-induced myocardial infarction in male albino rats. The pretreatment with squalene at 2% level along with feed significantly reduced the isoproterenol-induced rise in the levels of plasma diagnostic marker enzymes (ALT, AST, LDH and CPK). It counteracted isoproterenol-induced lipid peroxidation in plasma and heart tissue, and maintained the level of reduced glutathione in the heart tissue at near normalcy. Supplementation of squalene also exerted membrane stabilizing action against isoproterenol-induced myocardial infarction by maintaining the activities of membrane-bound ATPases (Na+, K+ ATPase and Ca2+ ATPase) in heart tissue and the mineral status (sodium, potassium and calcium) in plasma and heart tissue at near normal levels. The cardioprotective effect of squalene might be ascribable to its antioxidant nature and membrane stabilizing property.
The present study examined the antiulcer effect of glucosamine on mucosal antioxidant defense system in ibuprofen-induced peptic ulcer in male albino rats. The number of lesions in the gastric mucosa, volume of gastric juice, acid output, pepsin activity, lipid peroxides, reduced glutathione content and the activities of glutathione dependent antioxidant enzymes (glutathione peroxidase and glutathione-S-transferase) and antiperoxidative enzymes (catalase and superoxide dismutase) were determined. Prior oral administration of glucosamine significantly prevented the ibuprofen-induced increases in the number of lesions in the gastric mucosa, volume of gastric juice and acidity. It also maintained the activity of pepsin at near normal level. Oral pretreatment of glucosamine exerted a significant antioxidant effect by preventing ibuprofen-induced lipid peroxidation and by maintaining the level of reduced glutathione and the activities of mucosal antioxidant enzymes at near normalcy. The results of the present investigation indicate that the antiulcer activity of glucosamine is related to its ability to neutralize the hydrochloric acid secreted into the stomach and to its antioxidant capability to inhibit ibuprofen-induced lipid peroxidation.