Improvement of Lipids and Reduction of Oxidative Stress With Octacosanol After Taekwondo Training.

PURPOSE: Athletes in combat sports undergo rapid changes in body weight prior to competition in order to gain a size advantage over their opponent. However, these large weight changes with concomitant high-intensity exercise training create poor lipid profiles and high levels of oxidative stress, which can be detrimental to health and sport performance. Therefore, the purpose of this study was to investigate the ability of the nutritional supplement octacosanol to combat the physiological detriments that occur in taekwondo players during rapid weight loss with high-intensity exercise training. METHODS: A total of 26 male taekwondo players were randomly divided into 2 groups: An experimental group performed a 5% weight-loss and taekwondo training program with 40-mg octacosanol intake (OCT; n = 13) for 6 d, and a control group performed the same weight-loss and taekwondo training program with a placebo (CON; n = 13). RESULTS: There were significant (P < .05) group × time interactions for low-density lipoprotein and triglycerides, which significantly decreased (Δ18 [5] mg/dL and Δ80 [7] mg/dL, respectively), and high-density lipoprotein, which significantly increased (Δ10 [7] mg/dL), in the OCT group compared with the CON group. There were also significant (P < .05) group × time interactions for superoxide dismutase (SOD), glutathione peroxidase (GPx), and malondialdehyde (MDA), with SOD increasing (Δ226 [121] U/gHb) in the OCT group, while GPx decreased (Δ20 [13] U/gHb) and MDA increased (Δ72 [0.04] nmol/mL) in the CON group. CONCLUSION: These results suggest that octacosanol may be a beneficial supplement to protect against the poor cholesterol levels and oxidative stress that occurs during taekwondo training.

Double-stranded RNA mediates interferon regulatory factor 3 activation and interleukin-6 production by engaging Toll-like receptor 3 in human brain astrocytes.

Toll-like receptor 3 (TLR3) participates in the innate immune response by recognizing viral pathogens. In this study, human brain astrocytes were found to constitutively express TLR3, and this expression was increased by interferon-gamma (IFN-gamma) or double-stranded RNA (dsRNA). Treatment employing dsRNA in astrocytes induced IFN regulatory factor 3 (IRF3) phosphorylation, dimer formation and nuclear translocation followed by STAT1 activation. This treatment also activated nuclear factor-kappaB, p38 and c-Jun N-terminal kinase significantly, while activating extracellular signal-regulated kinase to a lesser extent. Treatment with anti-TLR3 antibody inhibited dsRNA-mediated interleukin-6 (IL-6) production. In the presence of mitogen-activated protein kinase inhibitors, astrocytes failed to secrete IL-6 in response to dsRNA treatment. Therefore, dsRNA-induced IL-6 production is dependent on mitogen-activated protein kinases and type I IFN production is dependent on IRF3 in brain astrocytes. These results suggest that brain inflammation, which produces inflammatory cytokines and type I IFNs, may enhance TLR3 expression in astrocytes. Additionally, upregulated TLR3 might modulate inflammatory processes by producing proinflammatory cytokines.

Human brain astrocytes mediate TRAIL-mediated apoptosis after treatment with IFN-gamma.

TNF-related apoptosis inducing ligand (TRAIL) expressions were studied in primary human brain astrocytes in response to pro-inflammatory cytokines. When astrocytes were treated with IL-1beta, TNF-alpha or IFN-gamma, TRAIL was induced in cultured fetal astrocytes. In particular, IFN-gamma induced the highest levels of TRAIL in cultured astrocytes. When astrocytes were pre-treated with IFN-gamma, they induced apoptosis in TRAIL-sensitive Peer cells. Our results suggest that IFN-gamma modulates the expression of TRAIL in astrocytes, which may enhance cytotoxic sensitivity of infiltrating immune cells or brain cells other than astrocytes during inflammation of brain.

CKD-712, (S)-1-(α-naphthylmethyl)-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, Inhibits the NF-κB Activation and Augments Akt Activation during TLR4 Signaling.

Since CKD-712 has been developed as an anti-inflammatory agent, we examined the effect of CKD-712 during TLR4 signaling. Using HEK293 cells expressing TLR4, CKD-712 was pre-treated 1 hr before LPS stimulation. Activation of NF-κB was assessed by promoter assay. The activation of ERK, JNK, p38, IRF3 and Akt was measured by western blotting. CKD-712 inhibited the NF-κB signaling triggered by LPS. The activation of ERK, JNK, p38 or IRF3 was not inhibited by CKD-712. On the contrary the activation of these molecules was augmented slightly. The activation of Akt with stimulation of LPS was also enhanced with CKD-712 pre-treatment at lower concentration, but was inhibited at higher concentration. We suggest that during TLR4 signaling CKD-712 inhibits NF-κB activation. However, CKD-712 augmented the activation of Akt as well as Map kinases. Therefore, we suggest that CKD-712 might have a role as an immunomodulator.

Ceramide increases Fas-mediated apoptosis in glioblastoma cells through FLIP down-regulation.

Ceramide is a physiologic regulator of growth and differentiation in mammalian cells. In this study, the relationship between ceramide and FLICE inhibitory protein (FLIP) in the induction of apoptosis in glioblastoma cell lines was investigated. We found that LN215 cells were slightly more sensitive to Fas-mediated apoptosis than LN319 cells, which were more sensitive to ceramide than LN215 cells. FLIP was expressed in LN319 and LN215 cells constitutively, and this expression decreased with treatment of ceramide in LN215 cells, which might cause LN215 cells to be more sensitive to Fas-mediated apoptosis at lower level stimulation. In LN319 cells FLIP levels were not modified by ceramide treatment and the level of cell death induced by anti-Fas antibody was not affected. Our results suggest that FLIP may be down-regulated by low levels of ceramide in LN215 cells, which causes LN215 cells to be more sensitive to Fas-mediated apoptosis, whereas LN319 cells remain resistant.