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1.
Youngsil Choi Mi-Jung Kwon Yangmi Lim Ji-Hye Yun Weontae Lee Eok-Soo Oh 《The Journal of biological chemistry》2015,290(27):16943-16953
Syndecans, a family of transmembrane heparansulfate proteoglycans, are known to interact through their transmembrane domains to form non-covalently linked homodimers, a process essential for their individual functions. Because all syndecan transmembrane domains are highly conserved and thus might mediate interactions between different members of the syndecan family, we investigated syndecan interactions in detail. All recombinant syndecan-2 and -4 protein variants containing the transmembrane domain formed not only sodium dodecyl sulfate (SDS)-resistant homodimers but also SDS-resistant heterodimers. Biochemical and structural data revealed that recombinant syndecan-2 and -4 formed intermolecular interactions in vitro, and the GXXXG motif in transmembrane domain mediated this interaction. When exogenously expressed in rat embryonic fibroblasts, syndecan-2 interacted with syndecan-4 and vice versa. Furthermore, bimolecular fluorescence complementation-based assay demonstrated specific hetero-molecular interactions between syndecan-2 and -4, supporting hetero-oligomer formation of syndecans in vivo. Interestingly, hetero-oligomerization significantly reduced syndecan-4-mediated cellular processes such as protein kinase Cα activation and protein kinase Cα-mediated cell adhesion as well as syndecan-2-mediated tumorigenic activities in colon cancer cells such as migration and anchorage-independent growth. Taken together, these data provide evidence that hetero-oligomerization produces distinct syndecan functions and offer insights into the underlying signaling mechanisms of syndecans. 相似文献
2.
Autophagy is an important catabolic program to respond to a variety of cellular stresses by forming a double membrane vesicle, autophagosome. Autophagy plays key roles in various cellular functions. Accordingly, dysregulation of autophagy is closely associated with diseases such as diabetes, neurodegenerative diseases, cardiomyopathy, and cancer. In this sense, autophagy is emerging as an important therapeutic target for disease control. Among the autophagy machineries, PIK3C3/VPS34 complex functions as an autophagy-triggering kinase to recruit the subsequent autophagy protein machineries on the phagophore membrane. Accumulating evidence showing that inhibition of PIK3C3/VPS34 complex successfully inhibits autophagy makes the complex an attractive target for developing autophagy inhibitors. However, one concern about PIK3C3/VPS34 complex is that many different PIK3C3/VPS34 complexes have distinct cellular functions. In this study, we have developed an in vitro PIK3C3/VPS34 complex monitoring assay for autophagy inhibitor screening in a high-throughput assay format instead of targeting the catalytic activity of the PIK3C3/VPS34 complex, which shuts down all PIK3C3/VPS34 complexes. We performed in vitro reconstitution of an essential autophagy-promoting PIK3C3/VPS34 complex, Vps34–Beclin1–ATG14L complex, in a microwell plate (96-well format) and successfully monitored the complex formation in many different conditions. This PIK3C3/VPS34 complex protein assay would provide a reliable tool for the screening of autophagy-specific inhibitors. 相似文献
3.
In Hwa Kim Won-Jin Lee Young-Kee Kim Byung-Keun Oh 《Biotechnology and Bioprocess Engineering》2016,21(5):689-693
In this study, we fabricated a novel recycled aggregate (RA) bio-carrier with sulfate-reducing bacteria (SRB) for the effective removal of the heavy metals Zn2+, Ni2+, and Cr6+ from contaminated seawater. By using only RA carriers, Zn2+, Ni2+, and Cr6+ could be removed up to 35.6, 11.0, and 61.3% and SRB-immobilized RA biocarriers could effectively lead to the removal of Zn2+, Ni2+, and Cr6+ up to 100.0, 98.0, and 87.8% for 100 ppm concentration of the heavy metals at 37°C, respectively. These results indicate that recycled aggregate bio-carriers with SRB hold great potential for use in the removal of cationic heavy metal species from marine environment. 相似文献
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Summary In the production of L-cysteine from D,L-ATC stability of the relevant enzymes produced byPseudomonas sp. was tested, and strategies to improve the stability of L-ATC hydrolase were investigated in view of water activity and ionic strength. Among the three enzymes which participate in L-cysteine production, i.e., ATC racemase, L-ATC hydrolase, and S-carbamyl-L-cysteine hydrolase, L-ATC hydrolase is the least stable. Various mixtures of salts and sorbitol were added to adjust the water activities of the tested solutions. As water activity decreased from 0.93 to 0.80, the stability of L-ATC hydrolase was sharply enhanced. In the absence of sorbitol the stability of L-ATC hydrolase increased in proportion to ionic strength. Even though enzyme stability was not good at a low ionic strength, it was enhanced by lowering water activity with addition of sorbitol. The half life of L-ATC hydrolase in sorbitol-salt mixtures increased by tenfold to twentyfold compared to that of a control. 相似文献
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Protective effect of serotonin on 6-hydroxydopamine- and dopamine-induced oxidative damage of brain mitochondria and synaptosomes and PC12 cells 总被引:3,自引:0,他引:3
Jong Weon Park Young Chul Youn Oh Sang Kwon Yoon Young Jang Eun Sook Han Chung Soo Lee 《Neurochemistry international》2002,40(3):769-233
The present study elucidated the effects of indoleamines (serotonin, melatonin, and tryptophan) on oxidative damage of brain mitochondria and synaptosomes induced either by 6-hydroxydopamine (6-OHDA) or by iron plus ascorbate and on viability loss in dopamine-treated PC12 cells. Serotonin (1-100 microM), melatonin (100 microM), and antioxidant enzymes attenuated the effects of 6-OHDA, iron plus ascorbate, or 1-methyl-4-phenylpyridinium on mitochondrial swelling and membrane potential formation. Serotonin and melatonin decreased the attenuation of synaptosomal Ca(2+) uptake induced by either 6-OHDA alone or iron plus ascorbate. Serotonin and melatonin inhibited the production of reactive oxygen species, formation of malondialdehyde and carbonyls, and thiol oxidation in mitochondria and synaptosomes and decreased degradation of 2-deoxy-D-ribose. Unlike serotonin, melatonin did not reduce the iron plus ascorbate-induced thiol oxidation. Tryptophan decreased thiol oxidation and 2-deoxy-D-ribose degradation but did not inhibit the production of reactive oxygen species and formation of oxidation products in the brain tissues. Serotonin and melatonin attenuated the dopamine-induced viability loss, including apoptosis, in PC12 cells. The results suggest that serotonin may attenuate the oxidative damage of mitochondria and synaptosomes and the dopamine-induced viability loss in PC12 cells by a decomposing action on reactive oxygen species and inhibition of thiol oxidation and shows the effect comparable to melatonin. Serotonin may show a prominent protective effect on the iron-mediated neuronal damage. 相似文献
9.
Han Gil Seo Nam-Jong Paik Shi-Uk Lee Byung-Mo Oh Min Ho Chun Bum Sun Kwon Moon Suk Bang 《PloS one》2015,10(6)
Background
Botulinum toxin type A is widely used for treating spasticity. Neuronox (Neu-BoNT/A), a newly manufactured botulinum toxin a, has not yet been investigated for its efficacy and safety in the treatment of post-stroke upper limb spasticity.Objective
We evaluated the efficacy and safety of Neuronox (Neu-BoNT/A) compared with BOTOX (onabotulinum toxin A) for treating post-stroke upper limb spasticity.Methods
In total, 196 stroke patients with moderate to severe upper limb spasticity were randomly assigned to either Neuronox or BOTOX intervention. The wrist flexors were mandatory and elbow, finger, and thumb flexors were optional muscles to be injected. Assessments were performed at baseline and 4, 8, and 12 weeks after the intervention. The primary outcome measure was the change from baseline of the Modified Ashworth Scale (MAS) at the wrist flexors at week 4. Secondary outcome measures included the change of MAS at each visit, response rate, Disability Assessment Scale (DAS), Carer Burden Scale, and Global Assessment of treatment benefit.Results
Primary outcome measures were -1.39±0.79 and -1.56±0.81 in the Neuronox and BOTOX groups, respectively. The difference was within the noninferiority margin of 0.45 (95% upper limit=0.40). There were no significant differences between the groups in the secondary outcome and safety measures, except the change of the MAS at the elbow flexors at week 12 (-0.88±0.75 in the Neuronox group, -0.65±0.74 in the BOTOX group; P=0.0429). Both groups showed significant improvements in the MAS, DAS, and Carer Burden Scale at weeks 4, 8, and 12.Conclusion
Neuronox showed equivalent efficacy and safety compared with BOTOX for treating post-stroke upper limb spasticity.Trial Registration
ClinicalTrials.gov NCT01313767 相似文献10.
Nicola L. Bird Matthew R. Olson Aeron C. Hurt Christine M. Oshansky Ding Yuan Oh Patrick C. Reading Brendon Y. Chua Yilun Sun Li Tang Andreas Handel David C. Jackson Stephen J. Turner Paul G. Thomas Katherine Kedzierska 《PloS one》2015,10(6)
CD8+ T cells directed against conserved viral regions elicit broad immunity against distinct influenza viruses, promote rapid virus elimination and enhanced host recovery. The influenza neuraminidase inhibitor, oseltamivir, is prescribed for therapy and prophylaxis, although it remains unclear how the drug impacts disease severity and establishment of effector and memory CD8+ T cell immunity. We dissected the effects of oseltamivir on viral replication, inflammation, acute CD8+ T cell responses and the establishment of immunological CD8+ T cell memory. In mice, ferrets and humans, the effect of osteltamivir on viral titre was relatively modest. However, prophylactic oseltamivir treatment in mice markedly reduced morbidity, innate responses, inflammation and, ultimately, the magnitude of effector CD8+ T cell responses. Importantly, functional memory CD8+ T cells established during the drug-reduced effector phase were capable of mounting robust recall responses. Moreover, influenza-specific memory CD4+ T cells could be also recalled after the secondary challenge, while the antibody levels were unaffected. This provides evidence that long-term memory T cells can be generated during an oseltamivir-interrupted infection. The anti-inflammatory effect of oseltamivir was verified in H1N1-infected patients. Thus, in the case of an unpredicted influenza pandemic, while prophylactic oseltamivir treatment can reduce disease severity, the capacity to generate memory CD8+ T cells specific for the newly emerged virus is uncompromised. This could prove especially important for any new influenza pandemic which often occurs in separate waves. 相似文献