Amyotrophic lateral sclerosis (ALS) is a rapidly progressive neurodegenerative disorder that affects upper and lower motor neurons. Since motor neurons target skeletal muscles, the maintenance system of muscles is disturbed in ALS; however, the mechanism by which this occurs is unknown. In the present study, we investigated the effects of ALS-associated P56S-vesicle-associated membrane protein-associated protein B (VAPB) (P56S-VAPB) on the IRE1-XBP1 pathway, which is involved in the unfolded protein response (UPR) of the mouse myoblast cell line (C2C12 cells). Experiments with C2C12 cells transfected with wild-type wt-VAPB and P56S-VAPB expression vectors showed reduced myotube formation and aberrant myonuclear position in cells expressing P56S-VAPB. Activity of the IRE1-XBP1 pathway in the cells visualized with the ERAI system revealed that the pathway was disrupted in cells expressing P56S-VAPB, whereas the IRE1-XBP1 pathway activity was enhanced in the differentiation process of normal C2C12 cells. These results suggest that disruption of the IRE1-XBP1 pathway is a cause for the reduced myotube formation in P56S-VAPB-expressing cells. The expression level of the VAPB protein has been reported to be reduced in the neurons of patients with ALS. Therefore, it is expected that the IRE1-XBP1 pathway is also impaired in muscle tissues of patients with ALS, which causes a disturbance in the muscle maintenance system.
The present study aimed to investigate the mechanism underlying the effect of adzuki bean extract on the differentiation of 3T3-L1 adipocytes. Treatment of these adipocytes with the extract significantly suppressed the expressions of the Pparγ, C/ebpα, and Fabp4 genes that are involved in adipogenesis (adipocyte differentiation). Oil Red O staining revealed that fat accumulation within these adipocytes is reduced significantly when the cells are treated with the extract. To explore the impact of adzuki bean extract on the differentiation of 3T3-L1 adipocytes, we investigated the effect of adzuki bean extract on the expression of cycle-related factors. We observed reduced expression of cyclin D1 mRNA and phosphorylated Rb (pRb), a downstream factor of cyclin D1 at 24 h after the application of a differentiation-inducing stimulus. Meanwhile, at 72 h after the stimulation, the expression of pRb increased with an increase in the amount of adzuki bean extract. The proliferation of cells declined significantly on treatment with the extract at 16 h after the stimulation but accelerated significantly at 72 h after the stimulation. These results suggest that adzuki bean extract contains an active ingredient that suppresses the differentiation of adipocytes. As a possible mechanism, the extract may alter the mitotic clonal expansion (MCE) which is essential for adipogenesis.
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