Purpose: Nitric oxide (NO) has been known as an important regulator of osteoblasts and periodontal ligament cell activity.This study was performed to investigate the relationship between NO-mediated cell death of human periodontal ligament fibroblasts (PDLFs) and N-methyl-D-aspartic acid (NMDA) receptor antagonist (+)-5-methyl-10, 11-dihydro-5H-dibenzo[a,d]cyclohepten-5, 10-imine hydrogen maleate (MK801).Methods: Human PDLFs were treated with various concentrations (0 to 4 mM) of sodium nitroprusside (SNP) with or without 200 μM MK801 in culture media for 16 hours and the cell medium was then removed and replaced by fresh medium containing MTS reagent for cell proliferation assay.Western blot analysis was performed to investigate the effects of SNP on the expression of Bax, cytochrome c, and caspase-3 proteins.The differences for each value among the sample groups were compared using analysis of variance with 95% confidence intervals.Results: In the case of SNP treatment, as a NO donor, cell viability was significantly decreased in a concentration-dependent manner.In addition, a synergistic effect was shown when both SNP and NMDA receptor antagonist was added to the medium.SNP treated PDLFs exhibited a round shape in culture conditions and were dramatically reduced in cell number.SNP treatment also increased levels of apoptotic marker protein, such as Bax and cytochrome c, and reduced caspase-3 in PDLFs.Mitogen-activated protein kinase signaling was activated by treatment of SNP and NMDA receptor antagonist.Conclusions: These results suggest that excessive production of NO may induce apoptosis and that NMDA receptor may modulate NO-induced apoptosis in PDLFs.
The proto‐oncogene protein DEK has been implicated in the t(6;9) chromosomal translocation associated with a subtype of acute myelogenous leukemia (AML), which results in the formation of a DEK‐CAN fusion protein. Histone acetylation is an important post‐translational modification which is involved in transcriptional regulation. In this study, we report that the acidic domain containing protein DEK interacts with histones and exerts a potent inhibitory effect on both p300 and PCAF‐mediated histone acetyltransferase activity and transcription. Using chromatin immunoprecipitation assays, we have demonstrated that the recruitment of DEK to the appropriate promoter induces the histone H3 and H4 hypoacetylation of chromatin. Collectively, our data illustrate the important regulatory role played by protein DEK in transcriptional regulation, and suggest that transcription‐regulating acidic domain regions may play a role in leukemogenesis.
Growth and differentiation factor 11 (GDF11) and myostatin (MSTN) are closely related transforming growth factor β (TGF-β) family members, but their biological functions are quite distinct. While MSTN has been widely shown to inhibit muscle growth, GDF11 regulates skeletal patterning and organ development during embryogenesis. Postnatal functions of GDF11, however, remain less clear and controversial. Due to the perinatal lethality of Gdf11 null mice, previous studies used recombinant GDF11 protein to prove its postnatal function. However, recombinant GDF11 and MSTN proteins share nearly identical biochemical properties, and most GDF11-binding molecules have also been shown to bind MSTN, generating the possibility that the effects mediated by recombinant GDF11 protein actually reproduce the endogenous functions of MSTN. To clarify the endogenous functions of GDF11, here, we focus on genetic studies and show that Gdf11 null mice, despite significantly down-regulating Mstn expression, exhibit reduced bone mass through impaired osteoblast (OB) and chondrocyte (CH) maturations and increased osteoclastogenesis, while the opposite is observed in Mstn null mice that display enhanced bone mass. Mechanistically, Mstn deletion up-regulates Gdf11 expression, which activates bone morphogenetic protein (BMP) signaling pathway to enhance osteogenesis. Also, mice overexpressing follistatin (FST), a MSTN/GDF11 inhibitor, exhibit increased muscle mass accompanied by bone fractures, unlike Mstn null mice that display increased muscle mass without fractures, indicating that inhibition of GDF11 impairs bone strength. Together, our findings suggest that GDF11 promotes osteogenesis in contrast to MSTN, and these opposing roles of GDF11 and MSTN must be considered to avoid the detrimental effect of GDF11 inhibition when developing MSTN/GDF11 inhibitors for therapeutic purposes.
The aim of this study was to evaluate and compare the osseointegration of zirconia implants in rabbit tibiae with and without 10-methacryloyloxydecyl dihydrogen phosphate (MDP) treatment.Twenty-eight rabbits received a total of 112 external hex-type implants made by the powder injection molding technique with and without MDP treatment before installation in the tibiae. The contact angles on the zirconia implants and zirconia discs before and after MDP application were evaluated. Removal torque (RT) and bone-implant contact (BIC) ratios were measured.The MDP treatment markedly enhanced the hydrophilicity and seemed to alter the topography and chemical composition of the implant and disc surface. As the healing time increases, the BIC and RT were increased in both groups. The MDP-treated implants exhibited higher BIC values than the control implants after 2 and 4 weeks of healing. The RT was higher in MDP-treated implants after 2 weeks of healing but not after 4 weeks of healing.The 10-MDP treatments made the surface more hydrophilic and enhanced the osseointegration of the implants in the early healing phase.
In addition to protease La (the lon gene product), Escherichia coli contains another ATP-dependent protease, Ti. This enzyme (approximately 340 kDa) is composed of two components, both of which are required for proteolysis. Both have been purified to homogeneity by conventional procedures using [3H]casein as the substrate. The ATP-stabilized component, A, has a subunit molecular weight of 80,000 upon gel electrophoresis in the presence of sodium dodecyl sulfate, but it behaves as a dimer (140 kDa) upon gel filtration. Component P, which is relatively heat stable, is inactivated by diisopropyl fluorophosphate and can be labeled with [3H] diisopropyl fluorophosphate. It has a subunit size of 23 kDa, but the isolated component behaves as a complex (260 kDa) of 10-12 subunits. The isoelectric point of component A is 7.0 and that of P is 8.2, and their amino acid compositions differ considerably. The purified enzyme has an ATPase activity that is stimulated 2-4-fold by casein and other protein substrates but not by nonhydrolyzed proteins. Component A also shows ATPase activity which can be stimulated by casein. Addition of component P (which lacks ATPase activity) inhibits basal ATP hydrolysis by A and makes this ATPase more responsive to casein. Although component P contains the serine active site for proteolysis, it shows no proteolytic activity in the absence of component A, Mg2+, and ATP or dATP. Other nucleoside triphosphates are not hydrolyzed and do not support proteolysis. Protease Ti has a Km for ATP of 210 microM for hydrolysis of both casein and ATP. Casein increases the Vmax for ATP without affecting the Km. A Mg2+ concentration of 5 mM is necessary for half-maximal rates of ATP and casein hydrolysis. Ca2+ and Mn2+ partially support these activities. Thus, protease Ti shares many unusual properties with protease La (e.g. coupled ATP and protein hydrolysis and protein-activated ATPase), but these functions in protease Ti are associated with distinct subunits that modify each other's activities.
셀룰로오스는 탄소와 수소 성분으로 이루어진 탄수화물 복합체로서 β-글루코오스 성분으로 이루어진 식물 세포벽의 주된 구성성분이다. 미더덕의 피부 각질에서 개발한 동물성 셀룰로오스 유도막에 1-2 MeV 에너지의 전자빔을 조사하여 C-C 결합보다 C-O 결합이 보다 증가함을 확인하였고, 여러 관련된 결과를 바탕으로 전자빔 조사에 의해 미세소관을 구성하는 셀룰로오스 미세원섬유들의 탈중합 과정을 일으킬 수 있었다. 셀룰로오스 합성복합체가 이동함으로써 셀룰로오스 섬유소들을 균일하고 미세하게 변형시킴으로써 골유도재생술을 위한 얇은 ㎛ 단위의 의료용 유도막으로 활용이 가능할 것으로 사료된다.
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