Characteristic pathological findings and effects of ecabet sodium in rat reflux esophagitis

AIM:To explore the pathological flndings in the entire esophagus in rats with reflux esophagitis, and the effects of ecabet sodium(ES).METHODS:A rat model of chronic acid reflux esophagitis was used.In the treatment group, ES was administered after surgery(n = 16).No drug was administered postoperatively to the esophagitis group(n = 9).Shamoperated rats were used as a control group(n = 5).Rats were sacriflced on day 7 after the operation.The epithelial thickness and leukocyte inflltration were examined in the upper, middle and lower areas of the esophagus.The survival rate, incidence of esophageal ulcer, and mean surface area and number of esophageal ulcers were determined in the esophagitis and ES groups.Esophageal histology was assessed in all three groups.RESULTS:Leukocyte infiltration in the esophagitis group was 26.3 ± 22.0 in the middle esophagus and 8.2 ± 4.9 in the upper esophagus, which was signiflcantly greater than that in the controls(1.3 ± 1.1 and 1.4 ± 1.0, respectively)(P < 0.05).The thickness of the epithelium in the esophagitis group was 210.8 ± 47.7 μm in the lower esophagus and 204.2 ± 60.1 μm in the middle esophagus, which was significantlygreater than that in the controls(26.0 ± 5.5 and 21.0 ± 6.5 μm, respectively)(P < 0.05).The mean number of ulcers per animal in the ES group in the entire esophagus was 5.4 ± 2.5, which was signiflcantly less than that in the esophagitis group(9.0 ± 3.5)(P < 0.05).The epithelial thickness in the ES group was 97.5 ± 32.2 μm in the lower esophagus, which was decreased compared with that in the esophagitis group(210.8 ± 47.7 μm)(P < 0.05).CONCLUSION:Mucosal inflammation extended to the upper esophagus close to the hypopharynx.Our study suggested that ES may have a useful defensive role in reflux esophagitis.

The ATPase activity of molecular chaperone HSP60 is inhibited by immunosuppressant mizoribine

The molecular chaperone HSP60 is a chaperonin homolog of GroEL. We had previously shown that the immunosuppressant mizoribine is bound directly to HSP60 and inhibited its chaperone activity. However, the inhibitory mechanisms of HSP60 by mizoribine have not yet been fully understood. In the present study, we investigated the influence of mizoribine on a folding cycle of HSP60 and co-chaperone HSP10. Our results showed that mizoribine inhibited the folding cycle of HSP60/HSP10. The ATPase activity of HSP60/HSP10 was decreased in the presence of mizoribine and the dissociation of HSP10 from HSP-60 was also decreased by mizoribine. The same functions of GroEL and/or GroES were slightly affected by mizoribine. Based on our findings, we discuss the inhibitory mechanisms of HSP60 by mizoribine.

Cytosolic chaperonin CCT possesses GTPase activity

Cytosolic chaperonin CCT (also known as TRiC) is a hetero-oligomeric cage-like molecular chaperone that assists in protein folding by ATPase cycle-dependent conformational changes. However, role of the nucleo-tide binding and hydrolysis in CCT-assisted protein folding is still poorly understood. We purified CCT by using ATP-Sepharose and other columns, and found that CCT possesses ability to hydrolyze GTP, with an activity level very similar to the ATPase activity. CCT was more resistant to proteinase K treatment in the presence of GTP or ATP. These results suggest that the GTPase activity of CCT may play a role in chaperone-assisted protein folding.