ABSTRACT
Amyloid accumulation in the brain is the major pathological hallmark of Alzheimer disease (AD). Amyloid beta (Aß) is cleared by the endosomal-autophagy-lysosomal system, which is impaired in AD pathogenesis by an unknown mechanism. Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been demonstrated to decrease the level of Aß in APP/PS1 mouse brain and to protect neurons by inhibiting the activation of microglia in vitro. The present study showed that PF11 was capable of increasing the uptake and degradation of oligomeric Aß in cultured microglia. Oligomeric Aß (oAß) interrupted the autophagy-lysosomal degradative system by regulating the nuclear translocation of transcription factor EB (TFEB), a master factor in lysosomal biogenesis. Conversion of Rab5 to Rab7, which is important for the mechanism of cargo progression from early to late endosomes, was also interrupted by high-concentration oAß. Notably, in the PF11-treated microglial cells, a dramatic increase of the lysosome-associated proteins and enzyme expression were observed, along with the intracellular pH steady state, indicating the improvement of lysosomal function. In addition, PF11 induced TFEB nuclear translocation in microglia treated with high-concentration oAß. Furthermore, PF11 was able to restore Rab conversion, suggesting an effective role of PF11 in the maturation of endosomes. These data provide evidence that PF11 can reverse the dysfunction of the endosomal-lysosomal system induced by high-concentration oAß in microglia, and this might be the main mechanism by which PF11 facilitates oAß clearance. Accordingly, we propose that PF11 should be considered as a potential agent for treating AD.
Subject(s)
Amyloid beta-Peptides/metabolism , Endosomes/metabolism , Ginsenosides/pharmacology , Lysosomes/metabolism , Microglia/drug effects , Neuroprotective Agents/pharmacology , Active Transport, Cell Nucleus , Animals , Basic Helix-Loop-Helix Leucine Zipper Transcription Factors/metabolism , Cell Nucleus/metabolism , Cells, Cultured , HEK293 Cells , Humans , Microglia/metabolism , Microglia/pathology , Rats , Rats, WistarABSTRACT
OBJECTIVE: To determine the prevalence of Mycoplasma suis infection in swine, swine-farm workers, and swine veterinarians in Shanghai, China. SAMPLE POPULATION: 172 swine and 65 workers and veterinarians from 19 commercial swine farms. PROCEDURES: Blood samples were collected from all study subjects. Blood samples were examined for the presence of M suis by means of compound and scanning electron microscopy. A species-specific PCR assay was developed for detection of M suis DNA extracted from blood samples. Relationships between infection status of swine and sex, age, geographic location, and clinical signs of disease were evaluated by use of a C(2) test. The phylogenetic relationship between partial 16S ribosomal RNA (rRNA) sequences from swine and human isolates of M suis was determined. RESULTS: 86% (148/172) of swine and 49% (32/65) of humans had positive PCR assay results for M suis infection. Swine infection status was not associated with any variable, with the exception of pyrexia and subcutaneous bleeding. The partial 16S rRNA sequences from human and swine isolates of M suis were 98% homologous and in the same phylogenetic cluster as a previously identified swine isolate of M suis. CONCLUSIONS AND CLINICAL RELEVANCE: A large proportion of swine and humans in close contact with those swine were infected with M suis in Shanghai, China. The close phylogenetic relationship between swine and human isolates of M suis suggested possible interspecies transmission; however, additional research is required to better assess that possibility.
