Hyun-Woo Suh

Publications (8)28.57 Total impact

• Article: VDUP1 exacerbates bacteremic shock in mice infected with Pseudomonas aeruginosa.

  Zheng-Hao Piao, Mi Sun Kim, Mira Jeong, Sohyun Yun, Suk Hyung Lee, Hu-Nan Sun, Hae Young Song, Hyun-Woo Suh, Haiyoung Jung, Suk Ran Yoon, Tae-Don Kim, Young-Ho Lee, Inpyo Choi
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  ABSTRACT: Vitamin-D3 upregulated protein-1 (VDUP1) is a stress response protein. Pseudomonas aeruginosa (P. aeruginosa) infection is a leading cause of death. Mice infected with live P. aeruginosa exhibit significantly decreased VDUP1 expression. However, the function of VDUP1 during P. aeruginosa-induced mouse bacteremic shock is unknown. To address the function of VDUP1 in P. aeruginosa-infected mice, we constructed a bacteremic shock model wherein both wild-type and VDUP1-deficient mice were infected intra-peritoneally with live P. aeruginosa. We found that VDUP1-deficient mice were more resistant to P. aeruginosa-induced bacteremic shock than wild-type mice, as shown by the increased survival, accelerated bacterial clearance and suppression of cytokine overproduction of the VDUP1-deficient mice. VDUP1 promoted the recruitment of neutrophils into the peritoneal cavities of infected mice. VDUP1 impeded the phagocytosis of non-opsonized P. aeruginosa via phosphatidylinositide 3-kinase (PI3K) pathway in macrophages. P. aeruginosa infection induced the generation of reactive oxygen species (ROS), and the increased production of ROS by the peritoneal cells of VDUP1-deficient mice was advantageous in clearing the bacteria. Overall, VDUP1 aggravates bacteremic shock; thus, VDUP1 can be considered a target molecule for the inhibition of P. aeruginosa-induced bacteremic shock.
  Cellular Immunology 11/2012; 280(1):1-9. · 1.97 Impact Factor
• Article: Vitamin D3 upregulated protein 1 suppresses TNF-α-induced NF-κB activation in hepatocarcinogenesis.

  Hyo-Jung Kwon, Young-Suk Won, Hyun-Woo Suh, Jun-Ho Jeon, Yan Shao, Suk-Ran Yoon, Jin-Woong Chung, Tae-Don Kim, Hwan-Mook Kim, Ki-Hoan Nam, Won-Kee Yoon, Dae-Ghon Kim, Jeong-Hwan Kim, Young-Sung Kim, Dae-Yong Kim, Hyoung-Chin Kim, Inpyo Choi
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  ABSTRACT: Vitamin D(3) upregulated protein 1 (VDUP1) is a candidate tumor suppressor, the expression of which is dramatically reduced in various tumor tissues. In this study, we found that VDUP1 expression is suppressed during human hepatic carcinogenesis, and mice lacking VDUP1 are much more susceptible to diethylnitrosamine-induced hepatocarcinogenesis compared with wild type mice. VDUP1-deficient tumors proliferated significantly more than wild type tumors and had corresponding changes in the expression of key cell cycle regulatory proteins. In addition, the hepatomitogen-induced response was associated with a considerable increase in the release of TNF-α and subsequent enhancement of NF-κB activation in VDUP1-deficient mice. When cells were treated with TNF-α, the VDUP1 level was markedly reduced, concomitant with elevated NF-κB activation. Furthermore, the overexpression of VDUP1 resulted in the robust suppression of TNF-α-activated NF-κB activity via association with HDAC1 and HDAC3. These results indicate that VDUP1 negatively regulates hepatocarcinogenesis by suppressing TNF-α-induced NF-κB activation.
  The Journal of Immunology 10/2010; 185(7):3980-9. · 5.79 Impact Factor
• Article: YC-1 enhances natural killer cell differentiation from hematopoietic stem cells.

  Sohyun Yun, Suk Hyung Lee, Yun Hee Kang, Mira Jeong, Mi Jeong Kim, Mi Sun Kim, Zheng-Hao Piao, Hyun-Woo Suh, Tae-don Kim, Pyung-Keun Myung, Suk-Ran Yoon, Inpyo Choi
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  ABSTRACT: NK cells play crucial roles in innate immunity and adaptive immunity. The detailed mechanisms, however, governing NK cell development remains unclear. In this study, we report that YC-1 significantly enhances NK cell populations differentiated from human umbilical cord blood hematopoietic stem cells (HSCs). NK cells increased by YC-1 display both phenotypic and functional features of fully mature NK (mNK) cells, but YC-1 does not affect the activation of mNK cells. YC-1 did not affect cGMP production and phosphorylation of STAT-5 which is essential for IL-15R signaling. On the other hand, YC-1 increased p38 MAPK phosphorylation during NK cell differentiation. Furthermore, p38 inhibitor SB203580 inhibited the differentiation of NK cells enhanced by YC-1. Taken together, these data suggest that YC-1 enhances NK cell differentiation through the activation of p38 MAPK which is involved in NK cell differentiation.
  International immunopharmacology 04/2010; 10(4):481-6. · 2.21 Impact Factor
• Source

  Available from: hku.hk

  Article: TXNIP regulates germinal center generation by suppressing BCL-6 expression.

  Yan Shao, Sang Yong Kim, Daesung Shin, Mi Sun Kim, Hyun-Woo Suh, Zheng-Hao Piao, Mira Jeong, Suk Hyung Lee, Suk Ran Yoon, Byung Ho Lim, Woo-Ho Kim, Jeong Keun Ahn, Inpyo Choi
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  ABSTRACT: The detailed mechanism driving the germinal center (GC) reaction to B cell lymphomagenesis has not been clarified. Thioredoxin interacting protein (TXNIP), also known as vitamin D3 up-regulated protein 1 which is an important tumor repressor, is involved in stress responses, redox regulation, and cellular proliferation. Here, we report that TXNIP has a potential role in the formation of GC in peripheral lymphoid organs where B lymphocytes divide rapidly. First, we compared changes in GC from wild type mice and Txnip(-/-) mice. After immunization, Txnip(-/-) mice exhibited higher expression level of BCL-6 and larger percentage of GC B cells with the reduction in antibody production and plasma cell numbers. In addition, Txnip(-/-) spleens had a much larger population which expressed Ki-67, a marker of cell proliferation, in the red pulp border than WT spleens. Furthermore, the expression of BCL-6 was decreased in TXNIP overexpressing cells and elevated in TXNIP deficient cells. Taken together, we conclude that TXNIP may contribute to the formation of GCs after immunization. During this process, TXNIP suppresses BCL-6 expression.
  Immunology letters 02/2010; 129(2):78-84. · 2.91 Impact Factor
• Article: VDUP1 mediates nuclear export of HIF1alpha via CRM1-dependent pathway.

  Daesung Shin, Jun-Ho Jeon, Mira Jeong, Hyun-Woo Suh, Seyl Kim, Hyoung-Chin Kim, Og-Sung Moon, Yong-Sung Kim, Jin Woong Chung, Suk Ran Yoon, Woo-Ho Kim, Inpyo Choi
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  ABSTRACT: Hypoxia-inducible factor 1alpha (HIF1alpha) is a critical transcriptional factor for inducing tumor metastasis, and stabilized under hypoxia but degraded by von Hippel-Lindau protein (pVHL) under normoxia. For the maximal degradation of HIF1alpha, it must be exported to the cytoplasm via an unidentified transporter. Here, we demonstrate that vitamin D3 up-regulated protein 1 (VDUP1) associates with the beta-domain of pVHL and enhances the interaction between pVHL and HIF1alpha to promote the nuclear export and degradation of HIF1alpha hypoxia-independently. Blocking of VDUP1 translocation either by leptomycin B or by nuclear export signal mutation inhibited the nuclear export of pVHL/HIF1alpha and relieved the destabilization of HIF1alpha. VDUP1 suppressed cell invasiveness and tumor metastasis, which were also recovered by blocking of nuclear export. Taken together, these findings indicate that VDUP1 is a novel tumor suppressor which mediates the nuclear export of pVHL/HIF1alpha complex to destabilize HIF1alpha.
  Biochimica et Biophysica Acta 06/2008; 1783(5):838-48. · 4.66 Impact Factor
• Article: Hypoxia-induced IL-18 increases hypoxia-inducible factor-1alpha expression through a Rac1-dependent NF-kappaB pathway.

  Jeongki Kim, Yan Shao, Sang Yong Kim, Seyl Kim, Hyun Keun Song, Jun Ho Jeon, Hyun Woo Suh, Jin Woong Chung, Suk Ran Yoon, Young Sang Kim, Inpyo Choi
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  ABSTRACT: Interleukin-18 (IL-18) plays pivotal roles in linking inflammatory immune responses and tumor progression and metastasis, yet the manner in which this occurs remains to be sufficiently clarified. Here we report that hypoxia induces the transcription and secretion of IL-18, which subsequently induces the expression of hypoxia-inducible factor-1alpha (HIF-1alpha). Mechanistically, IL-18 induces HIF-1alpha through the activity of the GTPase Rac1, which inducibly associates with the IL-18 receptor beta (IL-18Rbeta) subunit, via a PI3K-AKT-NF-kappaB-dependent pathway. Importantly, the knockdown of the IL-18Rbeta subunit inhibited IL-18-driven tumor cell metastasis. Collectively, these findings demonstrate a feed-forward pathway in HIF-1alpha-mediated tumor progression, in which the induction of IL-18 by hypoxia or inflammatory cells augments the expression of both HIF-1alpha and tumor cell metastasis.
  Molecular biology of the cell 03/2008; 19(2):433-44. · 5.98 Impact Factor
• Source

  Available from: ustc.edu.cn

  Article: Diverse functions of VDUP1 in cell proliferation, differentiation, and diseases.

  Sang Yong Kim, Hyun-Woo Suh, Jin Woong Chung, Suk-Ran Yoon, Inpyo Choi
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  ABSTRACT: Vitamin D3 up-regulated protein 1 (VDUP1) is a multifunctional protein involved in maintaining cellular homeostasis. VDUP1 is induced by a variety of stresses. Inversely, VDUP1 is often reduced in various tumor tissues and cell lines. Over-expression of VDUP1 inhibits cell proliferation through cell cycle arrest. VDUP1 interacts with thioredoxin (Trx) and negatively regulates the expression and antioxidant function of Trx which is involved in redox regulation. VDUP1-/- mice are more susceptible to carcinogenesis than wild-type mice and are defective in establishing immune system including the development and function of natural killer cells. Furthermore, VDUP1-/- mice show impaired Kreb cycle-mediated fatty acid utilization. In this review, we have discussed the multifunctional roles of VDUP1 in diverse cellular responses, in particular its relation to proliferation, apoptosis, differentiation, and diseases such as cancer and stress-related diseases.
  Cellular & molecular immunology 11/2007; 4(5):345-51. · 2.99 Impact Factor
• Article: Curcumin attenuates glutamate-induced HT22 cell death by suppressing MAP kinase signaling.

  Hyun-Woo Suh, Seongman Kang, Ki-Sun Kwon
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  ABSTRACT: Glutamate induces cell death by upsetting the cellular redox homeostasis, termed oxidative glutamate toxicity, in a mouse hippocampal cell line, HT22. Extracellular signal-regulated kinases (ERK) 1/2 are known key players in this process. Here we characterized the roles of both MAP kinases and cell cycle regulators in mediating oxidative glutamate toxicity and the neuroprotective mechanisms of curcumin in HT22 cells. c-Jun N-terminal kinase (JNK) and p38 kinase were activated during the glutamate-induced HT22 cell death, but at a later stage than ERK activation. Treatment with a JNK inhibitor, SP600125, or a p38 kinase inhibitor, SB203580, partly attenuated this cell death. Curcumin, a natural inhibitor of JNK signaling, protected the HT22 cells from glutamate-induced death at nanomolar concentrations more efficiently than SP600125. These doses of curcumin affected neither the level of intracellular glutathione nor the level of reactive oxygen species, but inactivated JNK and p38 significantly. Moreover, curcumin markedly upregulated a cell-cycle inhibitory protein, p21cip1, and downregulated cyclin D1 levels, which might help the cell death prevention. Our results suggest that curcumin has a neuroprotective effect against oxidative glutamate toxicity by inhibiting MAP kinase signaling and influencing cell-cycle regulation.
  Molecular and Cellular Biochemistry 05/2007; 298(1-2):187-94. · 2.06 Impact Factor