IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts

ArticleInternational Journal of Molecular Sciences. 21(1): 182. (2019)journal articl

A Preliminary Examination of Effect of Massage and Aroma Oil Massage in Foot Care Nursing

AbstractFoot care nursing is attracting attention as a medically effective treatment for the foot lesions caused by such problems as diabetes or aging. In this study, we experimentally examined how aromatherapy affects human brain functions during foot care nursing using near-infrared spectroscopy (NIRS). 11 subjects received both foot care nursing massages and aroma oil massages. We analyzed the changes in their oxygenated hemoglobin (oxy-Hb) concentrations based on their brain activity by t-tests, and the t-test results showed significant differences between two kinds of massages in both the somatosensory and prefrontal association areas. The oxy-Hb concentration in both massages with and without aroma oil also showed a tendency to decrease with time. Our questionnaire results showed that our subjects felt more comfortable and relaxed while receiving foot care nursing with aroma oils. These results suggest that aroma oil massages are an effective foot care nursing tool and that foot care nursing is a medically effective treatment

ALS-Linked P56S-VAPB Mutation Impairs the Formation of Multinuclear Myotube in C2C12 Cells

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

IRE1-XBP1 Pathway of the Unfolded Protein Response Is Required during Early Differentiation of C2C12 Myoblasts

In skeletal muscle, myoblast differentiation results in the formation of multinucleated myofibers. Although recent studies have shown that unfolded protein responses (UPRs) play an important role in intracellular remodeling and contribute to skeletal muscle differentiation, the involvement of IRE1–XBP1 signaling, a major UPR signaling pathway, remains unclear. This study aimed to investigate the effect of the IRE1–XBP1 pathway on skeletal muscle differentiation. In C2C12 cells, knockdown of IRE1 and XBP1 in cells remarkably suppressed differentiation. In addition, apoptosis and autophagy were dramatically enhanced in the XBP1-knockdown cells, highlighting the participation of IRE1–XBP1 in cell survival maintenance with differentiation stimuli during skeletal muscle differentiation. In myogenic cells, we demonstrated that the expression of CDK5 (cyclin-dependent kinase 5) is regulated by XBP1s, and we propose that XBP1 regulates the expression of MyoD family genes via the induction of CDK5. In conclusion, this study revealed that IRE1–XBP1 signaling plays critical roles in cell viability and the expression of differentiation-related genes in predifferentiated myoblasts and during the early differentiation phase

First Total Synthesis of (–)-Merrillianin

The first total synthesis of (–)-merrillianin (1), which is a natural sesquiterpene with a tri- fused structure having a cyclopentane ring and five- and seven-membered lactone parts, is demonstrated. This asymmetric total synthesis enabled the absolute stereo structure determination of naturally occurring (–)-1

The First Total Synthesis of Tanzawaic Acid B

The first total synthesis of (+)-tanzawaic acid B, a natural polyketide bearing a pentadienoic ester and octalin moiety, has been accomplished. The synthetic improvement from previous synthetic conditions facilitated our gram-scale synthesis of the chiral octalin that possesses seven stereogenic centers and that is the core skeleton of almost all of the tanzawaic acid family