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Taeyun Kwon Jinsung Park Jaemoon Yang Dae Sung Yoon Sungsoo Na Chang-Wan Kim Jin-Suck Suh Yong-Min Huh Seungjoo Haam Kilho Eom 《PloS one》2009,4(7)
Characterization and control of proteolysis of peptides by specific cellular protease is a priori requisite for effective drug discovery. Here, we report the nanomechanical, in situ monitoring of proteolysis of peptide chain attributed to protease (Cathepsin B) by using a resonant nanomechanical microcantilever immersed in a liquid. Specifically, the detection is based on measurement of resonant frequency shift arising from proteolysis of peptides (leading to decrease of cantilever''s overall mass, and consequently, increases in the resonance). It is shown that resonant microcantilever enables the quantification of proteolysis efficacy with respect to protease concentration. Remarkably, the nanomechanical, in situ monitoring of proteolysis allows us to gain insight into the kinetics of proteolysis of peptides, which is well depicted by Langmuir kinetic model. This implies that nanomechanical biosensor enables the characterization of specific cellular protease such as its kinetics. 相似文献
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Sang Kwang Lee Yongtae Kim Sung‐Soo Kim Jeong Hwa Lee Kun Cho Sang Sook Lee Zee‐Won Lee Kyung‐Hoon Kwon Young Hye Kim Haeyoung Suh‐Kim Jong Shin Yoo Young Mok Park 《Proteomics》2009,9(18):4389-4405
Mesenchymal stem cells (MSCs) are multipotent cells, which have the capability to differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle, and marrow stroma. However, they lose the capability of multi‐lineage differentiation after several passages. It is known that basic fibroblast growth factor (bFGF) increases growth rate, differentiation potential, and morphological changes of MSCs in vitro. In this report, we have used 2‐DE coupled to MS to identify differentially expressed proteins at the cell membrane level in MSCs growing in bFGF containing medium. The cell surface proteins isolated by the biotin–avidin affinity column were separated by 2‐DE in triplicate experiments. A total of 15 differentially expressed proteins were identified by quadrupole‐time of flight tandem MS. Nine of the proteins were upregulated and six proteins were downregulated in the MSCs cultured with bFGF containing medium. The expression level of three actin‐related proteins, F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2, was confirmed by Western blot analysis. The results indicate that the expression levels of F‐actin‐capping protein subunit alpha‐1, actin‐related protein 2/3 complex subunit 2, and myosin regulatory light chain 2 are important in bFGF‐induced morphological change of MSCs. 相似文献
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Hak Jin Kim Yong Woo Kim In Sook Lee Jong Woon Song Yeon Joo Jeong Seon Hee Choi Kyung Un Choi Kuen Tak Suh Byung Mann Cho 《Acta veterinaria Scandinavica》2009,51(1):30
Background
To test the hypothesis that triolein emulsion will increase vascular permeability of skeletal muscle. 相似文献66.
Hye Mi Kim Boonjae Jang Young Eun Cheon Myunghyun Paik Suh Junghun Suh 《Journal of biological inorganic chemistry》2009,14(1):151-157
Catalytic drugs based on target-selective artificial proteases have been proposed as a new paradigm in drug design. Peptide-cleavage
agents selective for pathogenic proteins of Alzheimer’s disease, type 2 diabetes mellitus or Parkinson’s disease have been
prepared using the Co(III) aqua complex (Co(III)cyclen) of 1,4,7,10-tetraazacyclododecane as the catalytic center. In the
present study, the Co(III) aqua complex (Co(III)oxacyclen) of 1-oxa-4,7,10-triazacyclododecane was examined in search of an
improved catalytic center for peptide-cleavage agents. An X-ray crystallographic study of [Co(oxacyclen)(CO3)](ClO4), titration of Co(III)oxacyclen, and kinetic studies on the cleavage of albumin, γ-globulin, lysozyme, and myoglobin by Co(III)oxacyclen
were carried out. Considerably higher proteolytic activity was observed for Co(III)oxacyclen in comparison with Co(III)cyclen,
indicating that better target-selective artificial metalloproteases would be obtained using Co(III)oxacyclen as the catalytic
center. The improved proteolytic activity was attributed to either steric effects or the increased Lewis acidity of the Co(III)
center. The kinetic data also predicted that side effects due to the cleavage of nontarget proteins by a catalytic drug based
on Co(III)oxacyclen would be insignificant. 相似文献
67.
Makoto Fujii Kye Sook Yi Myung Jong Kim Sang Hoon Ha Sung Ho Ryu Pann‐Ghill Suh Hitoshi Yagisawa 《Journal of cellular biochemistry》2009,108(3):638-650
Phosphorylation of phospholipase C‐δ1 (PLC‐δ1) in vitro and in vivo was investigated. Of the serine/threonine kinases tested, protein kinase C (PKC) phosphorylated the serine residue(s) of bacterially expressed PLC‐δ1 most potently. It was also demonstrated that PLC‐δ1 directly bound PKC‐α via its pleckstrin homology (PH) domain. Using deletion mutants of PLC‐δ1 and synthetic peptides, Ser35 in the PH domain was defined as the PKC mediated in vitro phosphorylation site of PLC‐δ1. In vitro phosphorylation of PLC‐δ1 by PKC stimulated [3H]PtdIns(4,5)P2 hydrolyzing activity and [3H]Ins(1,4,5)P3‐binding of the PLC‐δ1. On the other hand, endogenous PLC‐δ1 was constitutively phosphorylated and phosphoamino acid analysis revealed that major phosphorylation sites were threonine residues in quiescent cells. The phosphorylation level and the species of phosphoamino acid were not changed by various stimuli such as PMA, EGF, NGF, and forskolin. Using matrix‐assisted laser desorption/ionization time‐of‐flight (MALDI‐TOF) mass spectrometry, we determined that Thr209 of PLC‐δ1 is one of the constitutively phosphorylated sites in quiescent cells. The PLC activity was potentiated when constitutively phosphorylated PLC‐δ1 was dephosphorylated by endogenous phosphatase(s) in vitro. Additionally, coexpression with PKC‐α reduced serine phosphorylation of PLC‐δ1 detected by an anti‐phosphoserine antibody and PLC‐δ1‐dependent basal production of inositol phosphates in NIH‐3T3 cells, suggesting PKC‐α activates phosphatase or inactivates another kinase involved in PLC‐δ1 serine phosphorylation to modulate the PLC‐δ1 activity in vivo. Taken together, these results suggest that PLC‐δ1 has multiple phosphorylation sites and phosphorylation status of PLC‐δ1 regulates its activity positively or negatively depends on the phosphorylation sites. J. Cell. Biochem. 108: 638–650, 2009. © 2009 Wiley‐Liss, Inc. 相似文献
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Seonghan Kim Seo-Hyun Cho Ka Young Kim Ki Young Shin Hye-Sun Kim Cheol-Hyoung Park Keun-A Chang Sang Hyung Lee† Daeho Cho‡ Yoo-Hun Suh 《Journal of neurochemistry》2009,109(5):1483-1496
Although there is known to be a marked concentration of reactive microglia in the substantia nigra pars compacta (SNpc) of patients with Parkinson's disease (PD), a disorder in which α-synuclein plays a key pathogenic role, the specific roles of α-synuclein and microglia remains poorly understood. In this study, we investigated the effects of α-synuclein and the mechanisms of invasive microglial migration into the SNpc. We show that α-synuclein up-regulates the expressions of the cell adhesion molecule CD44 and the cell surface protease membrane-type 1 matrix metalloproteinase through the extracellular regulated kinases 1/2 pathway. These concurrent inductions increased the generation of soluble CD44 to liberate microglia from the surrounding extracellular matrix for migration. The effects of α-synuclein were identical in BV-2 murine microglial cells subjected to cDNA transfection and extracellular treatment. These inductions in primary microglial cultures of C57Bl/6 mice were identical to those in BV-2 cells. α-Synuclein-induced microglial migration into the SNpc was confirmed in vivo using a 6-hydroxydopamine mouse model of PD. Our data demonstrate a correlation between α-synuclein-induced phenotypic changes and microglial migration. With the recruitment of the microglial population into the SNpc during dopaminergic neurodegeneration, α-synuclein may play a role in accelerating the pathogenesis of PD. 相似文献