Weight loss may be a better approach for managing musculoskeletal conditions than increasing muscle mass and strength

To prevent or remedy musculoskeletal conditions, the relationship between obesity and the characteristics of muscle mass and strength need to be clarified. [Subjects and Methods] A total of 259 Japanese males aged 30–64 years were classified into 4 groups according to the Japanese obesity criteria. Body composition was evaluated, and handgrip strength and knee extensor strength were measured for the upper and lower extremities, respectively. Physical performance was evaluated with a jump test. [Results] Obesity was positively correlated with skeletal muscle mass index, percentage of whole-body fat, and leg muscle strength and negatively correlated with the percentage of muscle mass index, body weight-normalized handgrip strength, and knee extensor strength, and the jump test results. [Conclusion] Weight loss may be a better approach than increasing muscle mass and strength to improve musculoskeletal conditions in obese adult males.Key words: Obesity, Muscle mass, Muscle strength     

Comparison of neck and upper-limb muscle activities between able-bodied and paraplegic individuals during wheelchair propulsion on the ground

[Purpose] This study compared the muscle activities of the neck and upper-limb muscles between able-bodied individuals and persons with paraplegia during wheelchair propulsion on the ground. [Subjects and Methods] The muscle activities of the neck and upper-limb muscles of 8 normal individuals and 8 individuals with paraplegia were analyzed during wheelchair propulsion. The activities of the latissimus dorsi, pectoralis major, anterior/posterior deltoids, triceps brachii, extensor carpi radialis, and sternocleidomastoid muscles were assessed. [Results] The paraplegic group showed significantly higher sternocleidomastoid activity than the normal group. Latissimus dorsi activity was also higher in the paraplegia group than in the normal group, but the difference was not significant. There were no significant differences in the other muscle activities between groups. [Conclusion] Paraplegic patients tend to use the sternocleidomastoid and latissimus dorsi muscles with greater degrees of activity. Therefore, physiotherapists should not overlook the treatment of these muscles for paraplegic patients who are long-term wheelchair users.Key words: Wheelchair propulsion, Muscle activities, Upper-limb muscle     

Crystal structure of a central stalk subunit C and reversible association/dissociation of vacuole-type ATPase

The vacuole-type ATPases (V-ATPases) exist in various intracellular compartments of eukaryotic cells to regulate physiological processes by controlling the acidic environment. The crystal structure of the subunit C of Thermus thermophilus V-ATPase, homologous to eukaryotic subunit d of V-ATPases, has been determined at 1.95-A resolution and located into the holoenzyme complex structure obtained by single particle analysis as suggested by the results of subunit cross-linking experiments. The result shows that V-ATPase is substantially longer than the related F-type ATPase, due to the insertion of subunit C between the V(1) (soluble) and the V(o) (membrane bound) domains. Subunit C, attached to the V(o) domain, seems to have a socket like function in attaching the central-stalk subunits of the V(1) domain. This architecture seems essential for the reversible association/dissociation of the V(1) and the V(o) domains, unique for V-ATPase activity regulation.     

Ghrelin enhances the proliferating effect of thyroid stimulating hormone in FRTL-5 thyroid cells

Ghrelin regulates cell proliferation through the growth hormone secretagogue receptor (GHS-R). We confirmed the expression of GHS-R in FRTL-5 thyroid cells and investigated the effects of ghrelin in thyrocytes using FRTL-5 cells. Ghrelin increased intracellular calcium levels but not intracellular cyclic AMP levels. Ghrelin activated Erk within 2min, then activated Akt and STAT3. Erk phosphorylation was inhibited by the calcium inhibitor cyclopiazonic acid (CPA). Ghrelin alone did not stimulate FRTL-5 cell proliferation but enhanced the effects of thyroid stimulating hormone (TSH). Pretreatment with TSH potentiates the growth effects of ghrelin in thyroid cells, and p66Shc, a growth factor receptor adaptor protein, might mediate these synergistic effects. Ghrelin phosphorylated TSH-induced p66Shc, which was inhibited by CPA. Ghrelin did not affect the proliferation of ARO cells, which showed no increased expression of p66Shc after TSH treatment. Thus, ghrelin-induced intracellular calcium signaling enhanced the TSH-induced proliferation of thyrocytes, possibly mediated by the p66Shc pathway.     

Sec63 and Xbp1 regulate IRE1α activity and polycystic disease severity

The HSP40 cochaperone SEC63 is associated with the SEC61 translocon complex in the ER. Mutations in the gene encoding SEC63 cause polycystic liver disease in humans; however, it is not clear how altered SEC63 influences disease manifestations. In mice, loss of SEC63 induces cyst formation both in liver and kidney as the result of reduced polycystin-1 (PC1). Here we report that inactivation of SEC63 induces an unfolded protein response (UPR) pathway that is protective against cyst formation. Specifically, using murine genetic models, we determined that SEC63 deficiency selectively activates the IRE1α-XBP1 branch of UPR and that SEC63 exists in a complex with PC1. Concomitant inactivation of both SEC63 and XBP1 exacerbated the polycystic kidney phenotype in mice by markedly suppressing cleavage at the G protein–coupled receptor proteolysis site (GPS) in PC1. Enforced expression of spliced XBP1 (XBP1s) enhanced GPS cleavage of PC1 in SEC63-deficient cells, and XBP1 overexpression in vivo ameliorated cystic disease in a murine model with reduced PC1 function that is unrelated to SEC63 inactivation. Collectively, the findings show that SEC63 function regulates IRE1α/XBP1 activation, SEC63 and XBP1 are required for GPS cleavage and maturation of PC1, and activation of XBP1 can protect against polycystic disease in the setting of impaired biogenesis of PC1.     

Acidic polysaccharide of Panax ginseng regulates the mitochondria/caspase-dependent apoptotic pathway in radiation-induced damage to the jejunum in mice

Owing to its susceptibility to radiation, the small intestine of mice is valuable for studying radioprotective effects. When exposed to radiation, intestinal crypt cells immediately go through apoptosis, which impairs swift differentiation necessary for the regeneration of intestinal villi. Our previous studies have elucidated that acidic polysaccharide of Panax ginseng (APG) protects the mouse small intestine from radiation-induced damage by lengthening villi with proliferation and repopulation of crypt cells. In the present study, we identified the molecular mechanism involved. C57BL/6 mice were irradiated with gamma-rays with or without APG and the expression levels of apoptosis-related molecules in the jejunum were investigated using immunohistochemistry. APG pretreatment strongly decreased the radiation-induced apoptosis in the jejunum. It increased the expression levels of anti-apoptotic proteins (Bcl-2 and Bcl-X_S/L) and dramatically reduced the expression levels of pro-apoptotic proteins (p53, BAX, cytochrome c and caspase-3). Therefore, APG attenuated the apoptosis through the intrinsic pathway, which is controlled by p53 and Bcl-2 family members. Results presented in this study suggest that APG protects the mouse small intestine from irradiation-induced apoptosis through inhibition of the p53-dependent pathway and the mitochondria/caspase pathway. Thus, APG may be a potential agent for preventing radiation induced injuries in intestinal cells during radio-therapy such as in cancer treatment.     

Catalpol protects against 2,3,7,8‐tetrachlorodibenzo‐p‐dioxin‐induced cytotoxicity in osteoblastic MC3T3‐E1 cells

2,3,7,8‐tetrachlorodibenzo‐p‐dioxin (TCDD) is a well‐known environmental contaminant that produces a wide variety of adverse effects in humans. Catalpol, a major bioactive compound enriched in the dried root of Rehmannia glutinosa, is a major iridoid glycoside that alleviates bone loss. However, the detailed mechanisms underlying the effects of catalpol remain unclear. The present study evaluated the effects of catalpol on TCDD‐induced cytotoxicity in osteoblastic MC3T3‐E1 cells. Catalpol inhibited TCDD‐induced reduction in cell viability and increases in apoptosis and autophagic activity in osteoblastic MC3T3‐E1 cells. Additionally, pretreatment with catalpol significantly decreased the nitric oxide and nitrite levels compared with a control in TCDD‐treated cells and significantly inhibited TCDD‐induced increases in the levels of cytochrome P450 1A1 and extracellular signal‐regulated kinase. Pretreatment with catalpol also effectively restored the expression of superoxide dismutase and extracellular signal‐regulated kinase 1 and significantly enhanced the expression of glutathione peroxidase 4 and osteoblast differentiation markers, including alkaline phosphatase and osterix. Taken together, these findings demonstrate that catalpol has preventive effects against TCDD‐induced damage in MC3T3‐E1 osteoblastic cells.