Nordihydroguaiaretic acid, an antioxidant, inhibits transforming growth factor-beta activity through the inhibition of Smad signaling pathway

Transforming growth factor-beta (TGF-beta) and its family are potent and multi-functional cytokines that affect various fundamental biological events. TGF-beta has a unique signaling pathway that is carried by Smad family, and many recent studies showed the extensive crosstalk between Smad pathway and other signaling pathway. There were also clear evidences for the involvement of oxidative events in TGF-beta signaling pathway. To elucidate the role of oxidative events in carrying TGF-beta signals, we examined the effect of various antioxidants on TGF-beta activities in osteoblastic cell line. Among the examined compounds, we found nordihydroguaiaretic acid (NDGA) has a unique and strong inhibitory effect on various TGF-beta activities. Since the majority of TGF-beta activities are mediated by Smad, we questioned whether NDGA blocks the Smad signaling pathway. The result showed that NDGA inhibits the translocation of Smad2 to the nucleus. Further study revealed the strong inhibitory effect of NDGA on the phosphorylation of Smad2. This result may be important for designing chemical modulators of TGF-beta and its family related events and may provide new insights into the action mechanism of antioxidant.     

Transcriptional repression of cyclin-dependent kinase inhibitor p21 gene by phospholipase D1 and D2

Phospholipase D (PLD) is known to stimulate cell cycle progression and to transform murine fibroblast cells into tumorigenic forms, although the precise mechanisms are not elucidated. In this report, we demonstrated that both PLD1 and PLD2 repressed expression of cyclin-dependent kinase inhibitor p21 gene in an additive manner. The phospholipase activity of PLDs was important for the effect. PLD1 repressed the p21 promoter by decreasing the level of p53, whereas PLD2 via a p53-independent pathway through modulating Sp1 activity. Taken together, we suggest that PLD isozymes stimulate cell growth by repressing expression of p21 gene, which may ultimately lead to carcinogenesis.     

2-ketogluconic acid production and phosphate solubilization by Enterobacter intermedium

Enterobacter intermedium, isolated from grass rhizosphere, exhibited a strong ability to solubilize insoluble phosphate. This bacterium oxidized glucose to gluconic acid and sequentially to 2-ketogluconic acid (2-KGA), which was identified using HPLC and GC-MS. The ability of E. intermedium to solubilize phosphate and produce 2-KGA produce in broth medium containing different components was monitored with air and without air supply. With an air supply, the production of 2-KGA markedly increased to about 110 g/l at day 10 in media containing 0.2 M gluconic acid, while it was about 65 g/l without gluconic acid addition. With an air supply, the concentration of soluble phosphate significantly decreased to 200-250 mg/l in media containing 1% CaCO3, whereas it was about 1000 mg/l without CaCO3 addition. Without an air supply, the concentration of 2-KGA and phosphate were negligible throughout the culture period.     

2-Ketogluconic Acid Production and Phosphate Solubilization by <Emphasis Type="Italic">Enterobacter intermedium</Emphasis>

Enterobacter intermedium, isolated from grass rhizosphere, exhibited a strong ability to solubilize insoluble phosphate. This bacterium oxidized glucose to gluconic acid and sequentially to 2-ketogluconic acid (2-KGA), which was identified using HPLC and GC-MS. The ability of E. intermedium to solubilize phosphate and produce 2-KGA produce in broth medium containing different components was monitored with air and without air supply. With an air supply, the production of 2-KGA markedly increased to about 110 g/l at day 10 in media containing 0.2 M gluconic acid, while it was about 65 g/l without gluconic acid addition. With an air supply, the concentration of soluble phosphate significantly decreased to 200–250 mg/l in media containing 1% CaCO₃, whereas it was about 1000 mg/l without CaCO₃ addition. Without an air supply, the concentration of 2-KGA and phosphate were negligible throughout the culture period. RID= ID= <E5>Correspondence to: </E5>K.Y. Kim; <E5>email:</E5> kimkil&commat;chonnam.ac.kr Received: 21 August 2002 / Accepted: 25 September 2002     

Visceral fat accumulation determines postprandial lipemic response,lipid peroxidation,DNA damage,and endothelial dysfunction in nonobese Korean men

Visceral fat has been associated with multiple cardiovascular disease (CVD) risk factors. The aim of this study was to identify anthropometrical measures most closely associated with some well-known CVD risk factors. Because most Asians at risk have normal body mass index (BMI) according to Western standards, we studied healthy nonobese Korean males (n = 102; age: 36.5 +/- 0.8 years, BMI: 23.8 +/- 0.2 kg/m2). Visceral fat area (VFA) at the fourth lumbar vertebra was associated with increased postprandial triglyceride (TG) response (r = 0.53, P < 0.001) and with plasma malondialdehyde (MDA) (r = 0.36, P < 0.01) and PGF2alpha (r = 0.24, P < 0.05). When matched for BMI and age, men with high VFA (HVFA) (>/=100 cm2; n = 27) had higher blood pressure (P < 0.01), increased consumption of cigarettes (P < 0.01), and lower ratio of energy expenditure to calorie intake (P < 0.01) as compared with low VFA men (<100 cm2; n = 27). Men with HVFA showed higher TG, glucose, and insulin responses following fat and oral glucose tolerance tests respectively higher plasma concentrations of MDA (P < 0.001), urinary PGF2alpha (P < 0.05), and lymphocytes deoxyribonucleic acid tail moments (P < 0.01). Conversely, HVFA was associated with lower testosterone, insulin-like growth factor-1, and brachial artery flow-mediated dilation (P < 0.001). In conclusion, our data indicate that visceral fat accumulation, even in nonobese men, is a major factor contributing to increased CVD risk.     

A microbial fuel cell with improved cathode reaction as a low biochemical oxygen demand sensor

Mediator-less microbial fuel cells (MFC) enriched with oligotrophic microbes were optimized through enhancement of cathode reaction and lowering O₂ diffusion into the anode compartment as a low BOD sensor. The optimization of the MFC has greatly improved the maximum current and coulomb yield. The oligotroph-type MFC could be used as a low BOD sensor with high operational stability, good repeatability and reproducibility.     

High frequency somatic embryogenesis and plant regeneration in zygotic embryo cultures of Japanese honeysuckle

Japanese honeysuckle plant (Lonicera japonica Thunb.) is rich in iridoid secologanin and is a potentially useful model for the study of secologanin biosynthesis. Culture conditions for high frequency plant regeneration via somatic embryogenesis from zygotic embryo cultures and zygotic embryo-derived embryogenic cell suspension cultures of this species are described. Mature zygotic embryos formed embryogenic calluses at a frequency of 46.7% when cultured on Murashige and Skoog (MS) medium supplemented with 4.52 M 2,4-dichloro-phenoxyacetic acid (2,4-D). Cell suspension cultures were established with embryogenic calluses using liquid MS medium with 4.52 M 2,4-D. Upon plating onto MS basal medium, embryogenic cell suspension cultures produced numerous somatic embryos, which subsequently developed into plantlets at a frequency of 68%. Regenerated plantlets were transplanted to potting soil and grown to maturity in a greenhouse.     

Neural stem cells and neuro‐oncology: Quo vadis?

Conventionally, gliomas are assumed to arise via transformation of an intraparenchymal glial cell that forms a mass that then expands centrifugally, eventually invading surrounding tissues. We propose an alternative model in which gliomas arise via initiation and promotion of cells within the brain's subependymal layer or subventricular zone, the source of a recently characterized pool of neural cells with the properties of self-renewal and multipotentiality (i.e., stem cells) that persists into adulthood. In this model, the particular histological subtype of glioma would represent the effects of temporal and spatial environmental influences rather than the particular cell of origin and the disease's centrifugal point would be the subependymal layer. The implications of such a model are discussed.