Cathepsin D is involved in the clearance of Alzheimer's β-amyloid protein

AbstractThe cerebral deposition of 39–42 residue amyloid β-protein (Aβ) is a histopathological characteristic of Alzheimer's disease. The present study is aimed at finding proteinases responsible for the intracellular clearance of Aβ. The Aβ-degrading proteinase was purified from rat brain. Amino-terminal sequence analysis indicated the Aβ-degrading proteinase was cathepsin D. Purified cathepsin D hydrolyzed Aβ between Phe19 and Phe20. Cathepsin D is likely to be involved in the intracellular clearance of aggregatable Aβ, since Aβ fragments with Phe20 at the amino-terminus have been reported to be secreted from several lines of cultured cells

Effects of Tridocosahexaenoyl-Glycerol Emulsion on Proteinuria in Rats with Nephrotoxic Serum Nephritis

Background: Docosahexaenoic acid (DHA) is one of the n–3 polyunsaturated fatty acids and an important component of cell membrane phospholipids (PL). Nephrotoxic serum (NTS) nephritis was a worldwide model of the Goodpasture syndrome. We investigated the effects of tridocosahexaenoyl-glycerol (DHA-TG) emulsion on proteinuria in rats with NTS nephritis. Methods: Sixteen male Wistar rats weighing approximately 200 g were used. Twelve rats were treated with NTS via the tail vein and divided into 3 groups (groups A, B, and C). Another 4 rats treated with saline served as controls (group D). DHA-TG and soybean oil emulsions were intraperitoneally administered to the rats in groups A and B, respectively, 24 h prior to NTS injection, and 0, 1, 2, 3, 4, and 5 days after the injection. Saline was administered to the rats in groups C and D in the same manner. All rats were sacrificed on day 6 to obtain plasma and kidney samples. Analyses of urinary protein levels and fatty acid composition of plasma and kidney as well as histological examination of the kidneys were performed. Results: Urinary protein levels in group A were significantly lower than those in group C (35.0 ± 13.3 vs. 79.2 ± 11.8 mg/day on day 5, means ± SE, p Conclusions: These results suggest that the DHA-TG emulsion may have beneficial effects on NTS nephritis in the rat

Effects of Fatigue on Immune Function in Nurses Performing Shift Work

Objectives: We investigated the effects of fatigue on NK cell function and lymphocyte subpopulations in nurses performing shift work using a longitudinal design. Methods: Fifty-seven female nurses engaged in shift work at a hospital in Japan were selected for our study cohort. The hospital used a counterclockwise rotating three-shift system. Night shifts followed day shifts after a seven-hour interval. Immune parameters measured at the beginning of the day shift through to the end of the night shift were compared between two groups stratified by their level of fatigue. Statistical differences were evaluated after adjusting for baseline immune values and other demographic features. Results: Subjective feelings of fatigue increased progressively from the beginning of day shifts to the end of night shifts. From the beginning of day shifts to the end of night shifts, NK cell activity and CD16+CD56+ lymphocytes decreased, while CD3+ and CD4+ lymphocytes increased. The group with the greater increase in fatigue showed a larger decrease in NK cell activity and a larger increase in CD4+lymphocytes when compared with the group reporting less fatigue. These findings did not change after adjusting for demographic factors and sleep hours. Conclusion: Our data suggest that shift work has deleterious effects on NK cell function and that the effects depend on the degree of fatigue. Proper management of shift work may lessen fatigue in workers and also ameliorate many health problems experienced by shift workers

Central Role of Core Binding Factor β2 in Mucosa-Associated Lymphoid Tissue Organogenesis in Mouse

Mucosa-associated lymphoid tissue (MALT) is a group of secondary and organized lymphoid tissue that develops at different mucosal surfaces. Peyer\u27s patches (PPs), nasopharynx-associated lymphoid tissue (NALT), and tear duct-associated lymphoid tissue (TALT) are representative MALT in the small intestine, nasal cavity, and lacrimal sac, respectively. A recent study has shown that transcriptional regulators of core binding factor (Cbf) β2 and promotor-1-transcribed Runt-related transcription factor 1 (P1-Runx1) are required for the differentiation of CD3-CD4+CD45+ lymphoid tissue inducer (LTi) cells, which initiate and trigger the developmental program of PPs, but the involvement of this pathway in NALT and TALT development remains to be elucidated. Here we report that Cbfβ2 plays an essential role in NALT and TALT development by regulating LTi cell trafficking to the NALT and TALT anlagens. Cbfβ2 was expressed in LTi cells in all three types of MALT examined. Indeed, similar to the previous finding for PPs, we found that Cbfβ2-/- mice lacked NALT and TALT lymphoid structures. However, in contrast to PPs, NALT and TALT developed normally in the absence of P1-Runx1 or other Runx family members such as Runx2 and Runx3. LTi cells for NALT and TALT differentiated normally but did not accumulate in the respective lymphoid tissue anlagens in Cbfβ2-/- mice. These findings demonstrate that Cbfβ2 is a central regulator of the MALT developmental program, but the dependency of Runx proteins on the lymphoid tissue development would differ among PPs, NALT, and TALT