Hyon Park

Vitamin D3 supplementation modulates inflammatory responses from the muscle damage induced by high-intensity exercise in SD rats.

Vitamin D is an important factor for calcium and phosphorus homeostasis. A negative relationship has been observed between vitamin D status and diseases such as cancer, arthritis, diabetes, and muscle fiber atrophy. However, the relationship between vitamin D and prevention of skeletal muscle damage has not been clearly elucidated. The purpose of this study was to investigate the effects of vitamin D on exercise-induced muscle changes. Rats were divided into 3 groups: (1) sedentary control (C: n=10), (2) high-intensity exercise (HE: n=10), and (3) high-intensity exercise with vitamin D supplementation (HED: n=10; i.p. 1000 IU/kg body weight). Rats were trained for 30 min/day on treadmills (5 days/week for 8 weeks) with the running speed gradually increased up to 30 m/min at a 3° incline. At the end of the training period, the running speed was 38 m/min at a 5° incline. The high-intensity exercise significantly increased plasma creatine kinase (CK) and lactate dehydrogenase (LDH) activity. In addition, IL-6 and TNF-α levels as well as phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB were significantly increased. Vitamin D-treated rats showed a significant decrease in plasma CK level, phosphorylation of AMPK, p38, ERK1/2, IKK, and IκB, and gene expression of IL-6 and TNF-α. Furthermore, the protein expression of vitamin D receptor (VDR) was highly increased in the muscles of HED-treated rats, respectively. Therefore, we concluded that vitamin D may play a pivotal role in exercise-induced muscle damage and inflammation through the modulation of MAPK and NF-κB involved with VDR.

Chitooligosaccharide Induces Mitochondrial Biogenesis and Increases Exercise Endurance through the Activation of Sirt1 and AMPK in Rats

By catabolizing glucose and lipids, mitochondria produce ATPs to meet energy demands. When the number and activity of mitochondria are not sufficient, the human body becomes easily fatigued due to the lack of ATP, thus the control of the quantity and function of mitochondria is important to optimize energy balance. By increasing mitochondrial capacity? it may be possible to enhance energy metabolism and improve exercise endurance. Here, through the screening of various functional food ingredients, we found that chitooligosaccharide (COS) is an effective inducer of mitochondrial biogenesis. In rodents, COS increased the mitochondrial content in skeletal muscle and enhanced exercise endurance. In cultured myocytes, the expression of major regulators of mitochondrial biogenesis and key components of mitochondrial electron transfer chain was increased upon COS treatment. COS-mediated induction of mitochondrial biogenesis was achieved in part by the activation of silent information regulator two ortholog 1 (Sirt1) and AMP-activated protein kinase (AMPK). Taken together, our data suggest that COS could act as an exercise mimetic by inducing mitochondrial biogenesis and enhancing exercise endurance through the activation of Sirt1 and AMPK.

Effects of vitamin D supplementation and circuit training on indices of obesity and insulin resistance in T2D and vitamin D deficient elderly women

[Purpose] The purpose of this study was to investigate the effects of vitamin D supplementation and circuit training on body composition, abdominal fat, blood lipids, and insulin resistance in T2D and vitamin D deficient elderly women. [Methods] Fifty-two elderly women were randomly assigned to either the vitamin D supplementation with circuit training group (D+T: n = 15), the circuit training group (T: n = 13), the vitamin D supplementation group (D: n = 11), or the control group (CON: n = 13). The subjects in D took vitamin D supplements at 1,200 IU per day for 12 weeks; the subjects in T exercised 3 to 4 times per week, 25 to 40 minutes per session for 12 weeks; and the subjects in D+T participated in both treatments. Subjects in CON were asked to maintain normal daily life pattern for the duration of the study. Body composition, abdominal fat, blood lipids, and surrogate indices for insulin resistance were measured at pre- and post-test and the data were compared among the four groups and between two tests by utilizing two-way ANOVA with repeated measures. The main results of the present study were as follows: [Results] 1) Body weight, fat mass, percent body fat, and BMI decreased significantly in T, whereas there were no significant changes in the variables in D and CON. Lean body mass showed no significant changes in all groups. 2) TFA and SFA decreased significantly in T, whereas there were no significant changes in the variables in D and CON. The other abdominal fat related variables showed no significant changes in all groups. 3) TC, TG, HDL-C, and LDL-C showed improvements in T, whereas there were no significant changes in the variables in D and CON. 4) Fasting glucose, fasting insulin, and HOMA-IR tended to be lower in D+T. [Conclusion] It was concluded that the 12 weeks of vitamin D supplementation and circuit training would have positive effects on abdominal fat and blood lipid profiles in T2D and vitamin D deficient elderly women. Vitamin D supplementation was especially effective when it was complemented with exercise training.

Toll-like receptor 1 gene polymorphisms in childhood IgA nephropathy: a case-control study in the Korean population

Toll‐like receptors (TLRs) are innate immune mediators that stimulate nuclear factor kappa B and the inflammatory cytokines. TLR1 is expressed in renal tubular epithelial cells when the kidney is injured, but the role of TLR1 gene in glomerulonephritis has not been clearly elucidated. We aimed to investigate the association of TLR1 polymorphisms with immunoglobulin A nephropathy (IgAN) in children. One hundred and ninety pediatric patients with biopsy‐proven IgAN and 283 healthy control subjects were enrolled. Two single nucleotide polymorphisms of TLR1 gene [rs4833095 (missense, Asn248Ser) and rs5743557 (promoter, −414C/T)] were selected and genotyped by direct sequencing. For rs4833095, the C/T genotype in the codominant model (vs. the T/T genotype) [odds ratio (OR) = 2.11, 95% confidence interval (CI): 1.21–3.69, P = 0.009] and the genotype containing C allele (C/T and C/C) in the dominant model (vs. the T/T genotype) (OR = 1.97, 95% CI: 1.16–3.34, P = 0.012) were associated with an increased risk of IgAN. For rs5743557, the T/T genotype in the codominant model (vs. the C/C genotype) (OR = 1.74, 95% CI: 1.02–2.96, P = 0.041) appeared to be associated with IgAN risk. In haplotype analysis, the CT haplotype revealed an association with IgAN (codominant model, OR = 1.38, 95% CI: 1.06–1.80, P = 0.017; dominant model, OR = 1.76, 95% CI: 1.16–2.67, P = 0.008). After Bonferroni correction, the association of the genotypes of rs4833095 and the CT haplotype with IgAN risk remained significant. These findings suggest that TLR1 gene polymorphisms may affect IgAN susceptibility in Korean children.

A Systematic View of the MLO Family in Rice Suggests Their Novel Roles in Morphological Development, Diurnal Responses, the Light-Signaling Pathway, and Various Stress Responses

The Mildew resistance Locus O (MLO) family is unique to plants, containing genes that were initially identified as a susceptibility factor to powdery mildew pathogens. However, little is known about the roles and functional diversity of this family in rice, a model crop plant. The rice genome has 12 potential MLO family members. To achieve systematic functional assignments, we performed a phylogenomic analysis by integrating meta-expression data obtained from public sources of microarray data and real-time expression data into a phylogenic tree. Subsequently, we identified 12 MLO genes with various tissue-preferred patterns, including leaf, root, pollen, and ubiquitous expression. This suggested their functional diversity for morphological agronomic traits. We also used these integrated transcriptome data within a phylogenetic context to estimate the functional redundancy or specificity among OsMLO family members. Here, OsMLO12 showed preferential expression in mature pollen; OsMLO4, in the root tips; OsMLO10, throughout the roots except at the tips; and OsMLO8, expression preferential to the leaves and trinucleate pollen. Of particular interest to us was the diurnal expression of OsMLO1, OsMLO3, and OsMLO8, which indicated that they are potentially significant in responses to environmental changes. In osdxr mutants that show defects in the light response, OsMLO1, OsMLO3, OsMLO8, and four calmodulin genes were down-regulated. This finding provides insight into the novel functions of MLO proteins associated with the light-responsive methylerythritol 4-phosphate pathway. In addition, abiotic stress meta-expression data and real-time expression analysis implied that four and five MLO genes in rice are associated with responses to heat and cold stress, respectively. Upregulation of OsMLO3 by Magnaporthe oryzae infection further suggested that this gene participates in the response to pathogens. Our analysis has produced fundamental information that will enhance future studies of the diverse developmental or physiological phenomena mediated by the MLO family in this model plant system.

Association between interleukin-4 gene polymorphisms and intracerebral haemorrhage in Korean population

Interleukin‐4 (IL4) polymorphisms (rs2243250, rs2070874) were analysed in Korean patients with ischaemic stroke (IS) (n = 119) and intracerebral haemorrhage (ICH) (n = 79), and age‐matched controls (n =267, IS; n = 401, ICH) using direct sequencing. Both single nucleotide polymorphisms and their haplotypes were associated with ICH, but not IS.

Association of CXCL1 promoter polymorphism with ischaemic stroke in Korean population

This is a pilot study analysing association of chemokine gene polymorphisms (CXCL1, rs3117604; CXCL2, rs3806792; CCL2, rs2857656 and rs3760396; CCL5, rs2107538) in Korean patients with ischemic stroke (IS) (n = 120) and age‐matched controls (n = 267). The CXCL1 gene and particularly T allele of rs3117604 was associated with IS.

Clozapine inhibits cell survival-related genes in bone marrow cells.

SIR — Clozapine, an atypical antipsychotic agent, has been proven to be effective in the treatment of refractory schizophrenia. As the idiosyncratic clozapine-induced agranulocytosis occurs in 0.5–2% of the treated patients, the use of clozapine has been limited. Patients should monitor their white blood cell count during the treatment period. The mechanism of clozapine-induced agranulocytosis is not fully explained; however, it has been postulated as immunemediated mechanism and direct toxic effects. It has been demonstrated that the reactive nitrenium ion, a toxic metabolite, is produced from clozapine through myeloperoxidase-H2O2-dependent reaction, and then induces the apoptosis of neutrophils in vitro. In order to determine whether clozapine-treated bone marrow cells were susceptible to cell death, we compared the expression profiles of bone marrow cells between clozapineand vehicle (saline)-treated mice using cDNA microarray analysis. Clozapine (10 mg/kg, i.p.) was injected to male C57BL/6 mice (n1⁄4 5) for 2 weeks. The peripheral bloods in orbital venous plexus were sampled to count neutrophils, and bone marrow cells were collected from femurs and tibias. Total RNA was isolated immediately, and analysis of 7.4K Mice cDNA microarray (DigitalGenomics, Seoul, ROK) was performed according to the previous procedure. The cDNA microarray analysis was repeated twice. The global M method was used in this study to normalize intensity ratio of each gene expression. The expression level of selected genes was confirmed by RT-PCR using Gapdh as internal standard. The percentage of neutrophil was decreased in the clozapine-treated group (2.070.6%) compare to the vehicle-treated group (2.870.4%). After normalizing microarray data, expression ratio of 43 genes was higher than 1 (it indicated downregulation more than two times in the clozapine-treated group). However, expression ratio of 13 genes was lower than 1 (it showed upregulation more than two times in the clozapine-treated group) (data not shown). In this study, several cell survival-related genes were changed in clozapine-treated bone marrow cells (Figure 1). Rho guanine nucleotide exchange factor 7 (Arhgef7) gene showed the lowest ratio (2.8762) (Figure 1). Cell division cycle 42 (Cdc42) gene (1.5713) and calmodulin 1 (Calm1) gene (1.7757) were downregulated in the clozapine-treated group (Figure 1). Interestingly, Arhgef7 and Cdc42 interact to p21-activated kinase (Pak), which regulates cellular processes including rearrangement of the actin– myosin cytoskeleton, mitogen-activated protein kinase signaling pathway, and antiapoptotic pathway. The Arhgef7, known as Pak-interacting exchange factor beta, binds tightly to the conserved prolinerich Pak sequence. Thereafter, the interaction Cdc42 to Pak at the regulatory N-terminal induces a conformational change. It opens the Pak kinase domain and leads to autophosphorylation, and then exogenous substrate such as proapoptotic protein Bad is activated by phosphorylated Pak. Pak-mediated phosphorylation of Bad blocks cell death. Datta et al demonstrated that activated Akt (a serine–threonine kinase) phosphorylates Bad and promotes cell survival. Furthermore, phosphoinositide 3 (PI3) kinase, regulated by Ras, promotes cell survival through the Akt. Yano et al showed that calcium promotes cell survival through Ca2þ/Calm-dependent kinase, which activates Akt. Expression of Calm1 gene was also decreased in clozapine-treated bone marrow cells (Figure 1). After all, these data suggest the cascade of the survival signal of Ca2þ/Calm complex/Ras/PI3 kinase/Akt/Pak/Bad (Figure 2). Therefore, each downregulated gene by clozapine-treatment may block cell survival signaling (Figure 2). In addition, the expression of Rad21 gene was decreased (2.3951) in clozapine-treated bone marrow cells (Figure 1). Rad21 was known to repair doublestrand DNA breaks induced by ionizing radiation and endogenous cellular oxidative processes. The microenvironment stresses, such as hypoxia, hypoglycemia, and heat shock also reduced the expression level of the Rad21 mRNA. In conclusion, our study is the first report describing clozapine effects on bone marrow cells in vivo using cDNA microarray analysis. These results indicate that clozapine-induced agranulocytosis

Six week swimming followed by acute uptakes of ginsenoside Rg1 may affect aerobic capacity of SD rats.

[Purpose] The purpose of this study is to examine the effects of six-weeks of endurance swim training and short-term intake of Rg1 on the expression of related proteins as well as improvement of aerobic exercise capacity in 8-week-old male SD rats. [Methods] The groups were divided into placebo (NP, n=6), Rg1 (NRG, n=6), exercise+placebo (EP, n=7), and exercise+Rg1 (ERG, n=7). On completion of the 6-week swimming exercise, Rg1-intake groups were treated with acute uptakes (3 times within 24hrs) of Rg1. After the treatment, all groups were subjected to a swim to exhaustion test, and then the mass of muscle tissue, mRNA expression level and activity of citrate synthase (CS) were analyzed on plantaris. [Results] There were no differences in the effect of 6-week swimming exercise and short-term intake of Rg1 on body weight and muscle mass between groups. Although the CS mRNA expression was elevated in the exercise group and combined treatment group, there was no significant difference in CS activity. Acute uptakes of Rg1 did not affect swimming time to exhaustion, but it was increased by 235% and 314% by the 6-weeks of exercise and combined treatment of exercise and Rg1, respectively, which suggests that the combined treatment increased the effect on the capacity of aerobic exercise. [Conclusion] Based on these results, it was confirmed that even a short-term treatment of Rg1 can give an additive effect for improvement of exercise function, and additional studies are needed for the mechanisms and modes of its working.

Weight loss practice, nutritional status, bone health, and injury history: A profile of professional jockeys in Korea

[Purpose] The purpose of this study was to investigate the impact of weight loss practices on nutritional status, bone health, and injury history among Korean professional jockeys. [Methods] Forty-three male jockeys completed a questionnaire to assess their weight loss practices. Of these, 10 jockeys were selected for in-depth assessment of their nutritional status, bone health, and injury history. [Results] The questionnaires revealed that 81.4% of jockeys lost weight every week mainly by dieting and/or exercising. None of the jockeys consumed enough food during the weight loss period. Two jockeys were diagnosed with osteopenia and one was diagnosed with osteoporosis. Only history of fracture showed a significant correlation with low bone mineral density. All jockeys had more than one injury experience throughout their career. Fracture was the most common type of injury, occurring during practice and/or competition and caused mainly by difficulties in handling the horses. [Conclusion] Professional jockeys in Korea use extreme weight loss methods. Their repeated periods of poor nutritional intake may result in seriously low bone mineral density, which may aggravate injuries sustained during horse races. Implementation of balanced dietary programs and delivery of health education on weight management are urgently required.