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71.
72.
Kshitij Gupta Hyunbum Jang Kevin Harlen Anu Puri Ruth Nussinov Joel P. Schneider Robert Blumenthal 《Biophysical journal》2013
We have investigated the membrane destabilizing properties of synthetic amphiphilic cationic peptides, MAX1 and MAX35, which have the propensity to form β-hairpin structures under certain conditions, and a control non-β-hairpin-forming peptide MAX8V16E. All three peptides bind to liposomes containing a mixture of zwitterionic POPC and negatively charged POPS lipids as determined by Zeta potential measurements. Circular dichroism measurements indicated folding of MAX1 and MAX35 in the presence of the POPC/POPS liposomes, whereas no such folding was observed with MAX8V16E. There was no binding or folding of these peptides to liposomes containing only POPC. MAX1 and MAX35 induced release of contents from negatively charged liposomes, whereas MAX8V16E failed to promote solute release under identical conditions. Thus, MAX1 and MAX35 bind to, and fold at the surface of negatively charged liposomes adopting a lytic conformation. We ruled out leaky fusion as a mechanism of release by including 2 mol % PEG-PE in the liposomes, which inhibits aggregation/fusion but not folding of MAX or MAX-induced leakage. Using a concentration-dependent quenching probe (calcein), we determined that MAX-induced leakage of liposome contents was an all-or-none process. At MAX1 concentrations, which cause release of ∼50% of the liposomes that contain small (Rh <1.5 nm) markers, only ∼15% of those liposomes release a fluorescent dextran of 40 kDa. A multimeric model of the pore is presented based on these results. Atomistic molecular dynamics simulations show that barrels consisting of 10 β-hairpin MAX1 and MAX35 peptides are relatively more stable than MAX8V16E barrels in the bilayer, suggesting that barrels of this size are responsible for the peptides lytic action. 相似文献
73.
Hyehyeon Lee Jin Bae SohnSoo Shin Kim Kyung Lib Jang 《Biochemical and biophysical research communications》2013
We here report a simple assay system for DNA methyltransferase (DNMT) inhibitors based on the HBx-induced DNA methylation of E-cadherin. A stable cell line named G1 was generated by co-transfecting E-cadherin luciferase reporter and HBx-expression plasmid into HepG2 cells. Treatment of G1 cells with DNMT inhibitors, 5-azacytidine, 5-aza-2′-deoxycytidine, and procainamaid, dose-dependently inhibited DNA methylation of E-cadherin promoter in the reporter, resulting in up-regulation of luciferase levels and its enzyme activity. Treatment with all-trans retinoic acid that is known to inhibit DNMT expression, also induced similar effects. Our system can be useful for development of epi-drugs targeting DNA methylation in malignancies. 相似文献
74.
Keun Sam Jang Yong-Woon Jung Phillip S. Sherman Carole A. Quesada Guie Gu David M. Raffel 《Bioorganic & medicinal chemistry letters》2013,23(6):1612-1616
A new cardiac sympathetic nerve imaging agent, [18F]4-fluoro-m-hydroxyphenethylguanidine ([18F]4F-MHPG), was synthesized and evaluated. The radiosynthetic intermediate [18F]4-fluoro-m-tyramine ([18F]4F-MTA) was prepared and then sequentially reacted with cyanogen bromide and NH4Br/NH4OH to afford [18F]4F-MHPG. Initial bioevaluations of [18F]4F-MHPG (biodistribution studies in rats and kinetic studies in the isolated rat heart) were similar to results previously reported for the carbon-11 labeled analog [11C]4F-MHPG. The neuronal uptake rate of [18F]4F-MHPG into the isolated rat heart was 0.68 ml/min/g wet and its retention time in sympathetic neurons was very long (T1/2 >13 h). A PET imaging study in a nonhuman primate with [18F]4F-MHPG provided high quality images of the heart, with heart-to-blood ratios at 80–90 min after injection of 5-to-1. These initial kinetic and imaging studies of [18F]4F-MHPG suggest that this radiotracer may allow for more accurate quantification of regional cardiac sympathetic nerve density than is currently possible with existing neuronal imaging agents. 相似文献
75.
Jeong Ah Hwang Mun Kyung Hwang Yongwoo Jang Eun Jung Lee Jong-Eun Kim Mi Hyun Oh Dong Joo Shin Semi Lim Geun og Ji Uhtaek Oh Ann M. Bode Zigang Dong Ki Won Lee Hyong Joo Lee 《The Journal of nutritional biochemistry》2013,24(6):1096-1104
Abnormal regulation of Ca2+ mediates tumorigenesis and Ca2+ channels are reportedly deregulated in cancers, indicating that regulating Ca2+ signaling in cancer cells is considered as a promising strategy to treat cancer. However, little is known regarding the mechanism by which Ca2+ affects cancer cell death. Here, we show that 20-O-β-d-glucopyranosyl-20(S)-protopanaxadiol (20-GPPD), a metabolite of ginseng saponin, causes apoptosis of colon cancer cells through the induction of cytoplasmic Ca2+. 20-GPPD decreased cell viability, increased annexin V-positive early apoptosis and induced sub-G1 accumulation and nuclear condensation of CT-26 murine colon cancer cells. Although 20-GPPD-induced activation of AMP-activated protein kinase (AMPK) played a key role in the apoptotic death of CT-26 cells, LKB1, a well-known upstream kinase of AMPK, was not involved in this activation. To identify the upstream target of 20-GPPD for activating AMPK, we examined the effect of Ca2+ on apoptosis of CT-26 cells. A calcium chelator recovered 20-GPPD-induced AMPK phosphorylation and CT-26 cell death. Confocal microscopy showed that 20-GPPD increased Ca2+ entry into CT-26 cells, whereas a transient receptor potential canonical (TRPC) blocker suppressed Ca2+ entry. When cells were treated with a TRPC blocker plus an endoplasmic reticulum (ER) calcium blocker, 20-GPPD-induced calcium influx was completely inhibited, suggesting that the ER calcium store, as well as TRPC, was involved. In vivo mouse CT-26 allografts showed that 20-GPPD significantly suppressed tumor growth, volume and weight in a dose-dependent manner. Collectively, 20-GPPD exerts potent anticarcinogenic effects on colon carcinogenesis by increasing Ca2+ influx, mainly through TRPC channels, and by targeting AMPK. 相似文献
76.
Seongho Jang Eu Ddeum Park Hyung Joo Suh Sang Hun Lee Jin Soo Kim 《Bioscience, biotechnology, and biochemistry》2013,77(10):1716-1722
To investigate the activity of fermented deer antler on exercise endurance capacity, we evaluated endurance capacity in five-week-old male BALB/c mice by administering the fermented deer antler extract (FA) or the non-fermented deer antler extract (NFA) and then subjected the mice to exercise in the form of swimming. The mice administered 500?mg/kg/day of FA showed a significant increase in swimming time compared with mice administered placebo (16.55?min vs. 21.64?min, P?<?0.05). Serum lactate dehydrogenase (LDH), the marker of the liver and muscle damage, was significantly lower in FA groups. However, NFA groups did not show significantly different swimming time or serum LDH from that of the control group. Moreover, the FA-500 group had significantly higher hepatic superoxide dismutase (SOD) activity after forced swimming than the control and NFA groups (P?<?0.05). These findings suggest that fermentation may increase the exercise endurance capacity of the deer antler. 相似文献
77.
Jae-Myun Ryu Gwi Yeong Jang Dongsun Park Koan Sik Woo Tae Myoung Kim Heon Sang Jeong 《Bioscience, biotechnology, and biochemistry》2013,77(12):2101-2108
ABSTRACTBenign prostatic hyperplasia (BPH) is commonly observed in men > 50 years worldwide. Phytotherapy is one of the many treatment options. Sorghum (Sorghum bicolor L.) contains various health-improving phytochemicals with antioxidant and inhibitory activities on cell proliferation, both in vitro and in vivo. To confirm the effects of Donganme sorghum ethyl-acetate extract (DSEE) on BPH, we induced BPH in Spragye–Dawley rats using exogenous testosterone. We measured prostate weight, examined prostrates histopathologically, and analyzed mRNAs associated with male hormones and proteins associated with cell proliferation in the prostate. DSEE inhibited weight gain of the prostate; decreased mRNA expressions of androgen receptor and 5α-reductase II; and improved histopathological symptoms, the protein-expressed ratio of Bax/Bcl-2, and the oxidative status of BPH induced by testosterone in SD rats. Therefore, DSEE may have potential as a preventive or therapeutic agent against BPH. 相似文献
78.
Seung Ho Baek Min-Chul Jang Moonho Son Si Wouk Kim Hoon Cho Young Ok Kim 《Journal of applied phycology》2013,25(4):1055-1064
The algicidal effects of the thiazolidinedione derivative TD49 on Heterosigma akashiwo and Chattonella marina (Raphidophyceae) were assessed, and the response of the planktonic community and environment to the algicide was evaluated in a microcosm, quantifying 12 L. The abundance of over 80 % of H. akashiwo and C. marina declined in a day significantly in microcosms to which TD49 was added (final concentration 2 μM), and this was correlated with an abrupt decline in the culture pH. The number of protists (i.e., ciliates) other than H. akashiwo and C. marina gradually increased with time in the TD49 treatments, implying that the decline in numbers of H. akashiwo and C. marina cells resulting from TD49 treatment was a major factor in the growth of the other organisms. However, TD49 may be toxic to aquatic zooplankton communities, even though it is a highly selective algicide for harmful algae bloom species. The study indicates that TD49 is an effective agent for the control for H. akashiwo and C. marina blooms in enclosed and eutrophic water bodies. 相似文献
79.
Kyong-Jin Jung Hee-Seong Jang Jee In Kim Sang Jun Han Jeen-Woo Park Kwon Moo Park 《生物化学与生物物理学报:疾病的分子基础》2013,1832(12):1989-1997
Hydrogen sulfide (H2S) produced by cystathionine β-synthase (CBS) and cystathionine γ-lyase (CSE) in the transsulfuration pathway of homocysteine plays a number of pathophysiological roles. Hyperhomocysteinemia is involved in kidney fibrosis. However, the role of H2S in kidney fibrosis remains to be defined. Here, we investigated the role of H2S and its acting mechanism in unilateral ureteral obstruction (UO)-induced kidney fibrosis in mice. UO decreased expressions of CBS and CSE in the kidney with decrease of H2S concentration. Treatment with sodium hydrogen sulfide (NaHS, a H2S producer) during UO reduced UO-induced oxidative stress with preservations of catalase, copper-zinc superoxide dismutase (CuZnSOD), and manganese superoxide dismutase (MnSOD) expression, and glutathione level. In addition, NaHS mitigated decreases of CBS and CSE expressions, and H2S concentration in the kidney. NaHS treatment attenuated UO-induced increases in levels of TGF-β1, activated Smad3, and activated NF-κB. This study provided the first evidence of involvement of the transsulfuration pathway and H2S in UO-induced kidney fibrosis, suggesting that H2S and its transsulfuration pathway may be a potential target for development of therapeutics for fibrosis-related diseases. 相似文献
80.