Biomedical subjects

Sung Soo Chung

Publications and source records attributed to Sung Soo Chung.

12 recordsLinked to original sources

PubMed2006

SUMO-specific protease SUSP4 positively regulates p53 by promoting Mdm2 self-ubiquitination.

The p53 tumour suppressor has a key role in the control of cell growth and differentiation, and in the maintenance of genome integrity. p53 is kept labile under normal conditions, but in response to stresses, such as DNA damage, it accumulates in the nucleus for induction of cell-cycle arrest, DNA repair or apoptosis. Mdm2 is an ubiquitin ligase that promotes p53 ubiquitination and degradation. Mdm2 is also self-ubiquitinated and degraded. Here, we identified a novel cascade for the increase in p53 level in response to DNA damage. A new SUMO-specific protease, SUSP4, removed SUMO-1 from Mdm2 and this desumoylation led to promotion of Mdm2 self-ubiquitination, resulting in p53 stabilization. Moreover, SUSP4 competed with p53 for binding to Mdm2, also resulting in p53 stabilization. Overexpression of SUSP4 inhibited cell growth, whereas knockdown of susp4 by RNA interference (RNAi) promoted of cell growth. UV damage induced SUSP4 expression, leading to an increase in p53 levels in parallel with a decrease in Mdm2 levels. These findings establish a new mechanism for the elevation of cellular p53 levels in response to UV damage.

Animals↗

PubMed2006

Negative modulation of RXRalpha transcriptional activity by small ubiquitin-related modifier (SUMO) modification and its reversal by SUMO-specific protease SUSP1.

Retinoid X receptor alpha (RXRalpha) belongs to a family of ligand-activated transcription factors that regulate many aspects of metazoan life. Here we demonstrate that RXRalpha is a target substrate of a small ubiquitin-related modifier (SUMO)-specific protease, SUSP1, which is capable of controlling the transcriptional activity of RXRalpha. RXRalpha was modified by SUMO-1 in vivo as well as in vitro, and the Lys-108 residue within the IKPP sequence of RXRalpha AF-1 domain was identified as the major SUMO-1 acceptor site. Prevention of SUMO modification by Lys-to-Arg mutation led to an increase not only in the transcriptional activity of RXRalpha but also in the activity of its heterodimeric complex with retinoic acid receptor-alpha or peroxisome proliferator-activated receptor-gamma (PPARgamma). SUSP1 co-localized with RXRalpha in the nucleus and removed SUMO-1 from RXRalpha but not from androgen receptor or PPARgamma. Moreover, overexpression of SUSP1 caused an increase in the transcriptional activity of RXRalpha, whereas small hairpin RNA-mediated knockdown of endogenous SUSP1 led to a decrease in RXRalpha activity. These results suggest that SUSP1 plays an important role in the control of the transcriptional activity of RXRalpha and thus in the RXRalpha-mediated cellular processes.

Cell Nucleus↗

PubMed2006

CT analysis of the axis for transarticular screw fixation of rheumatoid atlantoaxial instability.

OBJECTIVE: To investigate the morphological characteristics of the axis of rheumatoid arthritis (RA) patients with atlantoaxial instability and to determine, by means of sagittal reconstructed computed tomography (CT), the suitability for atlantoaxial transarticular screw fixation. DESIGN AND PATIENTS: Twenty-seven patients, who had undergone reconstructed cervical spine CT scanning preoperatively and posterior atlantoaxial arthrodesis for atlantoaxial instability, were identified from a database for inclusion in this study. The isthmus height and internal height of the lateral mass of the axis were measured using digital imaging software. RESULTS: The mean isthmus height and internal height of the lateral mass of the axis in RA patients (n=14) were significantly lower than in non-RA patients (n=13) (P<0.01). A high-riding vertebral artery (VA) was present in 54% (15 joints, 9 patients) of the 28 atlantoaxial joints in the RA group and in 12% (3 joints, 2 patients) of the 26 atlantoaxial joints in the non-RA group (P<0.01). CONCLUSIONS: In RA patients, the axis showed more extensive thinning of the isthmus and lateral mass than in non-RA patients. A precise preoperative evaluation of screw trajectory using reconstruction CT imaging may be useful in atlantoaxial transarticular fixation, particularly for RA patients with atlantoaxial instability.

Arthritis, Rheumatoid↗

PubMed2006

PPARgamma gene transfer sustains apoptosis, inhibits vascular smooth muscle cell proliferation, and reduces neointima formation after balloon injury in rats.

OBJECTIVE: There is still debate as to whether antiatherosclerotic effect of PPARgamma ligands is dependant on PPARgamma gene itself or some other pathway. METHODS AND RESULTS: To investigate the effect of PPARgamma gene modulation on neointima formation after balloon injury, we delivered adenoviral vectors expressing the wild-type (WT) dominant negative (DN) PPARgamma, or a control gene (beta-galactosidase [BG]) into carotid artery after balloon injury in rosiglitazone (a PPARgamma ligand)-treated (R+) (3 mg/kg/d) and nontreated (R-) rats. Two weeks after gene delivery, in both R+ and R- animals, the PPARgamma-WT gene transfer showed a significantly lower intima-media ratio (IMR) than control group. Moreover, the delivery of a PPARgamma-DN form showed the highest IMR (in R+WT, 0.51+/-0.15; R+BG, 0.89+/-0.14; R+DN, 1.20+/-0.18, P<0.05 and in R-WT, 0.91+/-0.21; R-BG, 1.44+/-0.23; R-DN, 1.74+/-0.29, P<0.05). Proliferation and migration showed same result pattern as IMR. In addition, apoptotic indices were significantly higher in the PPARgamma-WT gene transferred group than in the PPARgamma-DN group. CONCLUSIONS: In vivo transfer of the PPARgamma-WT gene was found to inhibit smooth muscle proliferation, sustain apoptosis, and reduce neointima formation after balloon injury irrespective of rosiglitazone treatment. These results indicate that PPARgamma overexpression itself has a protective role against restenosis after balloon injury.

Animals↗

PubMed2006

Lumbar total disc replacement using ProDisc II: a prospective study with a 2-year minimum follow-up.

A lumbar total disc replacement (TDR) is believed to be a promising substitute in the surgical treatment for lumbar degenerative disc disease. The purpose of this study is to report the clinical and radiographic outcomes of 36 consecutive patients who underwent lumbar TDR using ProDisc II, and the factors associated with a better clinical outcome after a 2-year minimum follow-up. At the time of the latest follow-up, the success rate was 94% of 36 patients according to the criteria of the US Food and Drug Administration. Of the 10 patients unable to work preoperatively, 7 patients returned to work. Moreover, mean score on the visual analog scale for low back and leg pain improved significantly from 7.5 and 4.7 to 3.0 and 1.2, respectively (P<0.001). In addition, mean Oswestry disability index scores improved significantly from 69.2 to 21.0 (P<0.001). Mean disc height at the operative level increased significantly from 9.0 to 17.6 mm, and mean range of motion increased significantly from 9.7 to 12.7 degrees (P<0.01). Statistical analysis showed that the factors associated with a better clinical outcome were single level, and a higher postoperative segmental ROM at the operative level. At a minimum follow-up of 2 years, the lumbar TDR using ProDisc II showed excellent clinical and radiographic outcomes without any significant complication. However, future efforts need to be directed toward the evaluation of a larger number of patients with longer follow-up.

Adult↗

PubMed2006

The effect of lumbar total disc replacement on the spinopelvic alignment and range of motion of the lumbar spine.

A lumbar total disc replacement (TDR) is a type of motion-preserving surgery, which aims to restore and maintain the normal range of motion (ROM) and the sagittal balance of the spine. However, little is known regarding how the spinopelvic alignment and ROM of the lumbar spine are influenced by the lumbar TDR with ProDisc. This study retrospectively analyzed the sagittal alignment and ROM of the lumbar spine in 26 consecutive patients who had undergone the TDR with ProDisc with a minimum follow-up of 24 months. A standing lateral radiograph, which included the femoral heads and dynamic flexion-extension lateral radiographs of the spine were taken before surgery and at the follow-up visit. The radiological parameters included the sacral tilt, the pelvic tilt, and the lumbar lordosis. The segmental lordosis and ROM were also measured at each operative level. Nineteen patients underwent a single-level TDR and 7 patients underwent a double-level TDR. The mean lumbar lordosis increased significantly from 30.5 degrees to 40.8 degrees in all patients who underwent TDR without any significant changes in the sacral tilt and pelvic tilt at the latest follow-up (P<0.05). In the patients who underwent single-level TDR, the mean segmental lordosis at the L5-S1 and L4-5 operative levels increased significantly from 15.8 degrees to 23.2 degrees and from 14.1 degrees to 24.9 degrees, respectively. The mean ROM at L5-S1 and L4-5 increased significantly from 7.1 degrees to 11.2 degrees and from 11.4 degrees to 14.6 degrees, respectively. The sagittal balance and ROM of the lumbar spine improved significantly after the lumbar TDR.

Adult↗

PubMed2005

Resistin is secreted from macrophages in atheromas and promotes atherosclerosis.

OBJECTIVE: Resistin belongs to a family of cysteine-rich secreted polypeptides that are mainly produced by monocytes/macrophages in humans. Recently, high concentrations of resistin were shown to induce vascular endothelial dysfunction and vascular smooth muscle cell proliferation. We examined if resistin was secreted from macrophages locally in atheromas and if it affected vascular cell function in human. METHODS AND RESULTS: Immunohistochemical staining of human vessels showed that aortic aneurysms exhibited resistin-positive staining areas along macrophage infiltration, while normal arteries and veins did not. Co-localization of resistin and CD68 (a marker for macrophages) was observed in immunofluorescent double staining of aneurysms. Resistin mRNA was expressed much higher in cultured monocytes/macrophages than in human vascular smooth muscle cells (VSMCs) and human umbilical venous endothelial cells (HUVECs). This suggested that the resistin in aneurysms originates from macrophages within the vessels. To determine the effects of resistin on atherosclerosis, HUVECs and human VSMCs were incubated with resistin (10-100 ng/mL for 4 approximately 24 h). In HUVECs, plasminogen activator inhibitor (PAI)-1 release was assayed by ELISA, while the PAI-1 and endothelin (ET)-1 mRNA levels were analyzed by Northern blotting. Both were increased significantly with resistin treatment by factors of 1.3-2.5 (p<0.05). Migratory activity of VSMCs measured by scratched wound assay also increased significantly (1.6 times, p<0.05). In summary, macrophages infiltrating atherosclerotic aneurysms secrete resistin, and resistin affects endothelial function and VSMC migration. CONCLUSIONS: Resistin secreted from macrophages may contribute to atherogenesis by virtue of its effects on vascular endothelial cells and smooth muscle cells in humans.

Actins↗

PubMed2005

Strategies for assaying deubiquitinating enzymes.

A general method for assaying deubiquitinating enzymes (DUBs) has been developed. This new method employs an indirect enzyme assay for determining the activity of DUBs using a linear fusion of polyHis-glutathione-S-transferase-ubiquitin-ecotin (His-GST-Ub-ecotin) as a substrate. Because ecotin, a trypsin inhibitor protein from Escherichia coli, is heat stable, the activity of DUBs can be assayed indirectly by determining the ability of ecotin to inhibit trypsin after incubation of any DUB with His-GST-Ub-ecotin followed by heating at 100 degrees. In the substrate construction, His-GST fusion to Ub was used for facilitation of the substrate purification as well as for assisting the heat precipitation of His-GST-Ub and uncleaved His-GST-Ub-ecotin, as Ub itself is also heat stable. This method can also be used for assaying the proteases that process Ub-like proteins (Ubls) using the substrates, in which Ub is replaced by Ubls.

Amino Acid Sequence↗

PubMed2003

Deubiquitinating enzymes as cellular regulators.

Modification of proteins by the covalent attachment of ubiquitin is a key regulatory mechanism of many cellular processes including protein degradation by the 26S proteasome. Deubiquitination, reversal of this modification, must also regulate the fate and function of ubiquitin-conjugated proteins. Deubiquitinating enzymes catalyze the removal of ubiquitin from ubiquitin-conjugated substrate proteins as well as from its precursor proteins. Deubiquitinating enzymes occupy the largest family of enzymes in the ubiquitin system, implying their diverse function in regulation of the ubiquitin-mediated pathways. Here we explore the diversity of deubiquitinating enzymes and their emerging roles as cellular regulators.

Animals↗

PubMed2002

Antagonistic regulation of myogenesis by two deubiquitinating enzymes, UBP45 and UBP69.

Protein modification by ubiquitin is a dynamic and reversible process that is involved in the regulation of a variety of cellular processes. Here, we show that myogenic differentiation of embryonic muscle cells is antagonistically regulated by two deubiquitinating enzymes, UBP45 and UBP69, that are generated by alternative splicing. Both enzymes cleaved off ubiquitin from polyubiquitinated protein conjugates in vivo as well as from linear ubiquitin-protein fusions in vitro. In cultured myoblasts, the level of UBP69 mRNA markedly but transiently increased before membrane fusion, whereas that of UBP45 mRNA increased as the cells fused to form myotubes. Both myoblast fusion and accumulation of myosin heavy chain were dramatically stimulated by the stable expression of UBP69 but strongly attenuated by that of the catalytically inactive form of the protease, suggesting that the mutant enzyme acts dominant negatively on the function of the wild-type protease. In contrast, stable expression of UBP45 completely blocked both of the myogenic processes but that of inactive enzyme did not, indicating that the catalytic activity of the enzyme is essential for its inhibitory effects. These results indicate that differential expression of UBP45 and UBP69 is involved in the regulation of muscle cell differentiation.

Animals↗

PubMed2002

Involvement of protein phosphatase-1-mediated MARCKS translocation in myogenic differentiation of embryonic muscle cells.

Myristoylated alanine-rich C kinase substrate (MARCKS) translocates from the cytosol to the plasma membrane while mononucleated myoblasts fuse to form multinucleated myotubes. Here, we show that protein phosphatase-1-mediated dephosphorylation of MARCKS largely influences its subcellular localization and the fusion process. Treatment with okadaic acid or tautomycin, which are potent inhibitors of protein phosphatases and cell fusion, was found to reversibly block the MARCKS translocation. Moreover, the dephosphorylating activity against MARCKS markedly increased during myogenesis, and this increase was closely correlated with the membrane fusion of the cells. In addition, protein phosphatase-1 was identified as a major enzyme that is responsible for dephosphorylation of MARCKS. Furthermore, a mutation preventing MARCKS phosphorylation and thus facilitating MARCKS translocation resulted in promotion of the cell fusion. In contrast, overexpression of MARCKS carrying a mutation that blocks myristoylation and thus prevents the MARCKS translocation impaired the myoblast fusion. Together with the fact that MARCKS regulates the cytoskeleton dynamics by crosslinking the actin filaments in the plasma membrane and that myoblast fusion accompanies massive cytoskeleton reorganization, these results suggest that protein phosphatase-1-mediated MARCKS localization at the membrane is required for the fusion of embryonic muscle cells.

Amino Acid Sequence↗

PubMed2002

Factors affecting the surgical results of expansive laminoplasty for cervical spondylotic myelopathy.

We studied the outcome of expansive laminoplasty in 37 patients with cervical spondylotic myelopathy. Patients were divided into two groups according to the recovery rate (RR) - a 'good' group ( n=19), and a 'fair' group ( n=18). Patients in the good group showed a greater pre-operative Japanese Orthopaedic Association (JOA) score, a greater compression ratio, and a larger Pavlov ratio ( P<0.05). The presence of high signal intensity on MRI proved to be of no prognostic importance.

Adult↗