Corrigendum to: Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

The original version of this article contained misspelled name of author. The name of Figueroa Arturo is replaced with Arturo Figueroa.

Ursolic Acid-Induced Elevation of Serum Irisin Augments Muscle Strength During Resistance Training in Men

Ursolic acid (UA), a type of pentacyclic triterpenoid carboxylic acid purified from natural plants, can promote skeletal muscle development. We measured the effect of resistance training (RT) with/without UA on skeletal muscle development and related factors in men. Sixteen healthy male participants (age, 29.37+/-5.14 years; body mass index=27.13+/-2.16 kg/m2) were randomly assigned to RT (n=7) or RT with UA (RT+UA, n=9) groups. Both groups completed 8 weeks of intervention consisting of 5 sets of 26 exercises, with 10~15 repetitions at 60~80% of 1 repetition maximum and a 60~90-s rest interval between sets, performed 6 times/week. UA or placebo was orally ingested as 1 capsule 3 times/day for 8 weeks. The following factors were measured pre-and post-intervention: body composition, insulin, insulin-like growth factor-1 (IGF-1), irisin, and skeletal muscle strength. Body fat percentage was significantly decreased (p<0.001) in the RT+UA group, despite body weight, body mass index, lean body mass, glucose, and insulin levels remaining unchanged. IGF-1 and irisin were significantly increased compared with baseline levels in the RT+UA group (p<0.05). Maximal right and left extension (p<0.01), right flexion (p<0.05), and left flexion (p<0.001) were significantly increased compared with baseline levels in the RT+UA group. These findings suggest that UA-induced elevation of serum irisin may be useful as an agent for the enhancement of skeletal muscle strength during RT.

Combination treatment with 2-methoxyestradiol overcomes bortezomib resistance of multiple myeloma cells

Bortezomib is a proteasome inhibitor used for the treatment of relapsed/refractory multiple myeloma (MM). However, intrinsic and acquired resistance to bortezomib has already been observed in MM patients. In a previous report, we demonstrated that changes in the expression of mitochondrial genes lead to changes in mitochondrial activity and bortezomib susceptibility or resistance, and their combined effects contribute to the differential sensitivity or resistance of MM cells to bortezomib. Here we report that the combination treatment of bortezomib and 2-methoxyestradiol (2ME), a natural estrogen metabolite, induces mitochondria-mediated apoptotic cell death of bortezomib-resistant MM KMS20 cells via mitochondrial reactive oxygen species (ROS) overproduction. Bortezomib plus 2ME treatment induces a higher level of cell death compared with treatment with bortezomib alone and increases mitochondrial ROS and Ca2+ levels in KMS20 cells. Pretreatment with the antioxidant N-acetyl-L-cysteine scavenges mitochondrial ROS and decreases cell death after treatment with bortezomib plus 2ME in KMS20 cells. Moreover, we observed that treatment with bortezomib plus 2ME maintains the activation of c-Jun N-terminal kinase (JNK) and mitogen-activated protein kinase kinase kinase 4/7 (MKK4/7). Collectively, combination treatment with bortezomib and 2ME induces cell death via JNK-MKK4/7 activation by overproduction of mitochondrial ROS. Therefore, combination therapy with specific mitochondrial-targeting drugs may prove useful to the development of novel strategies for the treatment of bortezomib-resistant MM patients.

Prevention of IL-3 Deprivation Induced Apoptosis in Mast Cells by LPS / 대한해부학회지

Mast cells play a protective role in host defense against bacteria, and are found in high number at the host-environment interface. Stimulation of mast cells by bacterial cell wall components is essential for their protective effects against entero-bacterial infection. Mast cells have an extraordinarily long longevity in peripheral tissues compared to other types of blood cells. We undertook this study to reveal the mechanism underlying the prevention on IL-3 deprivation-induced apoptosis in mast cells by LPS. Bone marrow derived mast cells (BMMCs) were obtained from femurs of BALB/c mice and cultured under IL-3 stimulation for 4-6 weeks. At the same point when IL-3 was depleted, BMMCs were treated with LPS. To examine the effect of LPS, DNA electrophoresis, Western blotting, immunoflourescense staining, confocal microscopy, RT-PCR and immunoprecipitation were conducted. IL-3 deprivation reduced cellular viability and induced nuclear condensation and translocation of apoptosisassociated factors. However, LPS treatment prevented these IL-3 deprivation-induced apoptotic events. IL-3 deprivation downregulated representative antiapoptotic factors such as XIAP, 14-3-3, Bcl-2 and Bcl-xL. Expression level of these factors was maintained in BMMCs treated by LPS, which was similar to the level in the control cells. The Bim to Bcl-2 interaction was increased in IL-3 depleted cells, which was prevented by LPS treatment. It was also demonstrated that LPS induced the new expression of a cytokine-induced antiapoptotic factor anamorsin gene in BMMCs under IL-3 deprived condition. Taken together, LPS prevents IL-3 deprivation induced apoptosis in BMMCs via several antiapoptotic factors. This preventive mechanism of LPS on BMMCs apoptosis may contribute the long longevity of mast cells in the peripheral tissue.

zVAD-fmk, unlike BocD-fmk, does not inhibit caspase-6 acting on 14-3-3/Bad pathway in apoptosis of p815 mastocytoma cells

In a preliminary study, we found that benzyloxycarbonyl-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD- fmk), unlike Boc-aspartyl(OMe)-fluoromethylketone (BocD-fmk), at usual dosage could not prevent genistein-induced apoptosis of p815 mastocytoma cells. This study was undertaken to reveal the mechanism underlying the incapability of zVAD-fmk in preventing this type of apoptosis. We observed that 14-3-3 protein level was reduced in genistein-treated cells and that BocD-fmk but not zVAD-fmk prevented the reduction of 14-3-3 protein level and the release of Bad from 14-3-3. We also demonstrated that truncated Bad to Bcl-xL interaction in genistein- treated cells was prevented by BocD-fmk but not by zVAD-fmk treatment. Our data indicate that BocD- fmk, compared to zVAD-fmk, has a certain preference for inhibiting 14-3-3/Bad signalling pathway. We also elucidated that this differential efficacy of BocD-fmk and zVAD-fmk resulted from the different effect in inhibiting caspase-6 and that co-treatment of zVAD-fmk and caspase-6 specific inhibitor substantially prevented genistein-induced apoptosis. Our data shows that caspase-6 plays a role on Bad/14-3-3 pathway in genistein-induced apoptosis of p815 cells, and that the usual dose of zVAD-fmk, in contrast to BocD-fmk, did not prevent caspase-6 acting on 14-3-3/Bad-mediated event.