ABSTRACT
Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.
ABSTRACT
Adult olfactory neurogenesis plays critical roles in maintaining olfactory functions. Newly-generated neurons in the subventricular zone migrate to the olfactory bulb (OB) and determine olfactory discrimination, but the mechanisms underlying the regulation of olfactory neurogenesis remain unclear. Our previous study indicated the potential of APPL2 (adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 2) as a modulating factor for neurogenesis in the adult olfactory system. In the present study, we report how APPL2 affects neurogenesis in the OB and thereby mediates olfactory discrimination by using both in vitro neural stem cells (NSCs) and an in vivo animal model-APPL2 transgenic (Tg) mice. In the in vitro study, we found that APPL2 overexpression resulted in NSCs switching from neuronal differentiation to gliogenesis while APPL2 knockdown promoted neurogenesis. In the in vivo study, APPL2 Tg mice had a higher population of glial cells and dampened neuronal production in the olfactory system, including the corpus callosum, OB, and rostral migratory stream. Adult APPL2 Tg mice displayed impaired performance in olfactory discrimination tests compared with wild-type mice. Furthermore, we found that an interaction of APPL2 with Notch1 contributed to the roles of APPL2 in modulating the neurogenic lineage-switching and olfactory behaviors. In conclusion, APPL2 controls olfactory discrimination by switching the fate choice of NSCs via interaction with Notch1 signaling.
ABSTRACT
Abstract AIMS Previously, we verified that overtrained mice upregulated the TRB3 levels, its association with Akt, and the hepatic concentrations of glycogen. It is known that APPL1 can limit the interaction between TRB3 and Akt, playing an important role in the glucose homeostasis. Thus, we verified the effects of three overtraining protocols on the hepatic levels of APPL1 and APPL2. METHODS Rodents were divided into control (CT), overtrained by downhill running (OTR/down), overtrained by uphill running (OTR/up) and overtrained by running without inclination (OTR). The hepatic contents of APPL1 and APPl2 were measured by the immunoblotting technique. RESULTS Significant elevation of APPL1 observed in the OTR/down and OTR/up groups, as well as the tendency of increase (p=0.071) observed in the OTR group. CONCLUSION These results indicate that this particular protein is likely to participate in the glucose homeostasis previously observed in response to these OT protocols.(AU)
Subject(s)
Animals , Male , Mice , Adaptation, Physiological/physiology , Adaptor Proteins, Signal Transducing/metabolism , Hemostasis/physiology , Insulin/metabolism , Liver/physiology , Resistance Training , Mice, Inbred C57BLABSTRACT
Two mesophilic streptomycetes (S. violaceoruber and S. spiroverticillatus) were selected to study their Poly R-478 decolorization ability and lignocellulose solubilizing activity. Both strains were able to degrade Poly R-478 dye and ferulic acid during growth on a minimal salts medium. The Poly R-478 decolorizing activities of both strains were induced by adding different carbon sources to the culture media. S. violaceoruber could decolorize 63% of Poly R-478 after 24 h. Both strains could solubilize straw and produce acid-precipitable polymeric lignin (APPL) with different efficiency. From the major extracellular enzymes recovery of both strains on rice and wheat straw, we can predicate that the biodegradation process was partial indicating a possible utilization in biological delignification.
Subject(s)
Anthraquinones/metabolism , Lignin/metabolism , Polymers/metabolism , Streptomyces/metabolism , Biotransformation , Coumaric Acids/metabolism , Culture Media/chemistry , Oryza/metabolism , Plant Stems/metabolism , Streptomyces/growth & development , Triticum/metabolismABSTRACT
Objective To determine the role of APPL1,an adaptor protein,played in pancreatic β-cell.Methods APPL1 was overexpressed in INS-1 cells with adenovirus encoding APPL1.Western blot was conducted to measure protein cxprcssion.Propidium iodide/Hoechst staining was used to determine the cell apoptosis.Insulin secretion was measured by ELISA.Results Exposure of INS-1 cells to 20 mmol/L glucose or 30U/ml interleukin-1 β plus 20 ng/ml TNF-α 48 h induced β-cell apoptosis (P＜0.01) and impaired 2 h glucosestimulated insulin secretion (P＜ 0.01).Overexpression of APPL1 in INS-1 decreased cell apoptosis by 34.16％-42.79％ (P＜0.01) and increased glucose-induced insulin secretion by 1.39-2.20 folds compared with control groups (P＜0.05).Conclusion APPL1 decreases β-cell apoptosis and increases glucose-stimulated insulin secretion,and thus protects β-cell against high glucose or cytokines-induced dysfunction.
ABSTRACT
The purpose of the present work is to observe whether Tau protein Ser202/Thr205 is hyperphosphorylated in braintissues of diabetic mice and to study the effect of App17 peptide. Mouse diabetic model was produced with streptozotocin, andApp1 7 peptide as a treatment was injected subcutaneously into diabetic mice. Four weeks later, fixative was injected intravascu-larly into the mice, the brain was removed and crystat sections prepared. Immunohistochemical staining was done with AT-8. Inthe brains of diabetic mice positive AT-8 reacting neurons were numerous, darkly stained, and widely distributed in retrosplenialgranular cortex, hippocampus, thalamus et al. , while in normal mice and App17 peptide-treated diabetic mice positive cells werescarce and poorly stained. Tau protein is hyperphosphorylated at Scr202/Thr205 site and widely distributed in the brains of dia-betic mice, while App17 peptide can normalize the expression of AT-8 positive cells.