Expression of a 72-kDa heat shock protein, and its cytoprotective function, in gastric mucosa in cirrhotic rats

Background Portal hypertensive gastropathy (PHG) is a clinical entity that is observed frequently in patients with liver cirrhosis. In PHG, gastric mucosa is highly susceptible to mucosal injury caused by noxious agents. Many studies, including ours, have reported that a 72-kDa heat shock protein (HSP72) has a crucial cytoprotective function in gastric mucosa. In this study, we investigated the expression and cytoprotective effect of HSP72 on gastric mucosa in portal hypertensive rats.Methods PHG was produced by bile duct ligation (BDL) or carbon tetrachloride administration in male Sprague-Dawley rats. The expression of HSP72 in the gastric mucosa was evaluated by Western blotting. Induction of gastric mucosal HSP72 by 6-h water-immersion stress was compared between cirrhotic and control rats. Also, mucosal protective abilities against hydrochloric acid (HCl; 0.6N) following pretreatment with water-immersion stress to induce HSP72 were studied in both groups.Results Portal venous pressure was significantly higher in cirrhotic rats compared with control rats (P < 0.05). Baseline expression (before water-immersion stress) of mucosal HSP72 was significantly lower in cirrhotic rats compared with control rats. HCl-induced gastric mucosal lesions were significantly suppressed in control rats compared with cirrhotic rats, especially when HSP72 was preinduced by water-immersion stress.Conclusions These findings suggest that HSP72 in the gastric mucosa plays a crucial role with respect to cytoprotection; the induction of HSP72 may provide therapeutic strategies for protection against mucosal injury in PHG.     

MEK Activation Suppresses CPT11-Induced Apoptosis in Rat Intestinal Epithelial Cells Through a COX-2-Dependent Mechanism

Resistance to chemotherapeutic agents is one of the distinct features of cancer cells. We evaluate the role of activated MEK-ERK signaling in Camptotecin/irinotecan (CPT-11)-induced cell death using constitutively activated MEK1-transfected normal rat intestinal epithelial cells (IEC-caMEK cells). A CPT-11-induced inhibitory concentration of 50% was determined by WST assay. Apoptosis was evaluated by DNA staining and fragmented DNA analysis. Protein expressions were analyzed by western blotting. We also examined the role of cyclooxygenase-2 in the cell systems. IEC-caMEK cells possessed survival advantages compared to control cells. Apoptosis was remarkably suppressed in IEC-caMEK cells. Western blot analysis revealed increased expression of Bcl-2, Bcl-xL, Mcl-1, and COX-2 and decreased expression of Bak in IEC-caMEK cells. The COX-2 selective inhibitor ameliorated the antiapoptotic nature of IEC-caMEK cells. MEK activation suppressed CPT-11-induced apoptosis in IEC-caMEK cells via a COX-2- dependent mechanism. Therefore, MEK-ERK signaling may contribute to the drug-resistant nature of cancer cells.     

Soy protein reduces paraquat-induced oxidative stress in rats

The effect of soy protein, soy isoflavones and saponins on paraquat (PQ)-induced oxidative stress was investigated in rats. Rats were fed experimental diets containing casein (CAS), soy protein (SPI), and casein with soy isoflavones and saponins (CAS + IS). The diets were supplemented or not with 0.025% paraquat (CAS + PQ, SPI + PQ, and CAS + IS + PQ). The protective effects of soy protein, soy isoflavones, and saponins on paraquat-induced oxidative stress were examined. Ingestion of soy protein generally mitigated the lung enlargement (P = 0.076), loss of body weight (P = 0.051) and oxidation of liver lipid (P = 0.043) and glutathione (P = 0.035) induced by paraquat, although soy isoflavones and saponins did not. To determine whether soy protein exerted its antioxidative effects by preventing paraquat absorption from digestive organs, rats were fed CAS or SPI diets and orally administered a 12.5 g/L paraquat solution. Plasma, urine, and fecal paraquat concentrations did not differ between the two groups, indicating that soy protein did not prevent paraquat absorption. The present study suggests that intake of soy protein itself, but not soy isoflavones and saponins, reduces paraquat-induced oxidative stress in rats, although this effect was not due to reduced absorption of paraquat from digestive organs.