Keemin Woo - Academia.edu (original) (raw)

Papers by Keemin Woo

The Korean Journal of Internal Medicine, 2007

Background : Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat... more Background : Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. Methods : 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SPA and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. Results : LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SPA levels peaked at hour 6, declining thereafter. Conclusions : We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SPA , on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.

Research communications in molecular pathology and pharmacology, 2002

Alterations of the FHIT gene occur as frequent events in several human cancers. Replacement of ex... more Alterations of the FHIT gene occur as frequent events in several human cancers. Replacement of exogenous wild-type FHIT gene has been shown to induce suppression of tumorigenicity of human FHIT-negative cells in nude mice and aberrant FHIT transcripts have been observed in a variety of human solid tumors. In the presence study, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR) analysis to identify aberrant FHIT transcripts in 6 gastric cancer cell lines. In addition to the wild-type FHIT transcript, small-sized transcripts with various number and lengths were observed in all of the cell lines examined. Sequence analysis confirmed that different types of truncated transcripts included exonic deletions, insertions of intron 5 sequences between exons, and combinations of both. Most of these transcripts lacked exon 5 in which translation initiation codon is located. Aberrant transcripts with partial exonic deletions, resulting from activation of cryptic spli...

International journal of molecular medicine, 2012

Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits p... more Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits proliferation of various malignant cells. Here, we investigated whether juglone affects 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation through the phosphoinositol 3-kinase (PI3K) pathway. The results showed that TPA- and endothelial growth factor (EGF)-induced anchorage-independent colony formation were suppressed in a dose-dependent manner by treatment of JB6 CI41 mouse skin epidermal cells with juglone (2.5 and 5 µM). We demonstrated that juglone suppressed PI3K activity via direct binding to PI3K by sepharose 4B pull-down assay and western blot analysis. Juglone significantly suppressed TPA-induced protein kinase B (AKT) and c-Jun phosphorylation and c-fos activation, but not mitogen-activated protein-kinase kinase (MEK), extracellular signaling-regulated kinase (ERK) or 90 kDa ribosomal protein S6 kinase (RSK) phosphorylation. Juglone significantly blocked acti...

Molecular Medicine Reports, 2012

a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a de... more a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent non-collagenous matrix component in articular cartilage. ADAMTS12 has been observed in the cartilage, synovial fluid and serum of arthritic patients, and may play an important role in the pathogenesis of arthritis. In the present study, we investigated whether genetic polymorphisms of ADAMTS12 are associated with rheumatoid arthritis (RA). To observe the association between ADAMTS12 and RA, we genotyped three single nucleotide polymorphisms (SNPs) (rs1364044, intron C/T; rs10461703, intron C/T; rs25754, missense Thr1495Ile) of ADAMTS12 using a direct sequencing method in 303 RA patients and 495 control subjects. Multiple logistic regression models were performed to analyze the genetic data. SNPStats and SNPAnalyzer Pro programs were used to estimate the odds ratios, 95% confidence intervals and p-values. Bonferroni's correction (p c) was conducted to obtain a defined result. Of the three SNPs, the genotype frequency of rs10461703 was associated with the development of RA (p c =0.0024 in the co-dominant model; p c =0.0009 in the dominant model; p c =0.0006 in the log-additive model). The allele frequency of rs10461703 also showed a significant difference between RA and controls (p c <0.0001). The C allele frequency of rs10461703 was lower in the RA group (36.6%) compared to the control group (45.7%), whereas the T allele frequency of rs10461703 in the RA group (63.4%) was higher compared to that in the control group (54.3%). The other two SNPs (rs1364044 and rs25754) were not associated with the development of RA. However, we did not find any association between the three tested SNPs and RA patients according to clinical features, including erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor (+ and-) and bone erosion (+ and-). Our results suggest that ADAMTS12 may be a susceptibility gene for RA development.

Molecular and Cellular Biochemistry, 2012

Post-translational modification of peptidyl cis/ trans prolyl isomerase Pin1 is crucial in regula... more Post-translational modification of peptidyl cis/ trans prolyl isomerase Pin1 is crucial in regulation of gene stability. Pin1 phosphorylation at Ser 16 has been regarded as a marker for Pin1 isomerase activity and introduction of phosphorylation on Ser/Thr-Pro of substrate proteins is prerequisite for its binding activity with Pin1 and subsequent isomerization. Here, we found that 90 kDa ribosomal protein S6 kinase 2 (RSK2) could form a physical complex with Pin1, leading to phosphorylation of Pin1 at Ser 16 ex vivo and in vitro respectively. Intriguingly, Pin1 ?/? mouse embryonic fibroblasts (MEFs) exhibited significantly an increase in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced RSK2 phosphorylation with a marginal Pin1 phosphorylation compared with Pin1-/-MEFs. Moreover, TPA-induced Ser 16 Pin1 phosphorylation as well as RSK2 phosphorylation was considerably profound in RSK ?/? MEFs but not in RSK-/-MEFs. Consequently, knockdown of Pin1 using shRNA-Pin1 suppressed TPAinduced cell transformation in JB6 CI41 cells. Overall, these results indicate that Pin1 plays a critical role in TPA-induced tumorigenesis plausibly via physical interaction with RSK2 and reciprocal phosphorylation, therefore suggesting a potential therapeutic target for cancer treatment. Keywords Ribosomal S6 kinase 2 Á Peptidyl cis/trans prolyl isomerase Á Tumorigenesis Á 12-O-tetradecanoylphorbol-13-acetate Á Post-translational modification Abbreviations Pin1 Peptidyl-prolyl cis/trans isomerase RSK2 90 kDa ribosomal protein S6 kinase 2 MEFs Mouse embryonic fibroblasts TPA 12-O-tetradecanoylphorbol-13-acetate ERK Extracellular signal-regulated kinase MEK Mitogen-activated protein kinase

Experimental & Molecular Medicine, 1998

Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubat... more Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubation of cell cycle progression and/or apoptosis on proliferating mammalian cells. Our studies were focused on the cellular effects of nickel (II) acetate, DNAdamaging agent, on Chinese hamster ovary (CHO) cells. Fragmented DNAs were examined by agarose gel electrophoresis and cell cycle was determined by DNA flow cytometry using propidium iodide fluorescence. Apparent DNA laddering was observed in cells treated with 240 M nickel (II) and increased with a concentration-dependent manner. Tr e a t m e n t of nickel (II) acetate resulted in apoptosis which was accompanied by G 2 /M cell accumulation. Proportion of CHO cells in G 2 /M phase was also significantly increased in cells exposed to at least 480 M nickel (II) from 57.7% of cells in the G 0 / G 1 phase, 34.7% in the S phase, and 7.6 % in the G 2 /M phase for 0 M nickel (II), to 58.6%, 14.5%, and 26.9% for 640 M nickel (II). These findings suggest that nickel (II) can modulate cellular response through some common effectors involving in both apoptotic and cell cycle regulatory pathways.

Biochemical and Biophysical Research Communications, 2001

Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric... more Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, we have investigated the FHIT gene for loss of heterozygosity (LOH), aberrant transcripts, point mutations, and protein expression in 35 gastric adenocarcinomas. Allelic loss at D3S1300 was detected in 7 of 33 (21%) informative cases. Aberrant transcripts, with deletions and/or insertions, were observed in 20 of 35 (57.1%) cases and resulted from alternative splicing through exon skipping and/or insertion of the FHIT intron 5 sequence or activation of the cryptic splice site. Point mutations were not found in the FHIT coding region but detected in noncoding exon 2, 3, 4, or 5 of eight aberrant transcripts. Significant reduction of FHIT protein expression was observed in 22 of 35 (62.9%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrant FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.

Research communications in molecular pathology and pharmacology, 2002

The fragile histidine triad (FHIT) gene located in human chromosome 3p14.2 is a candidate tumor s... more The fragile histidine triad (FHIT) gene located in human chromosome 3p14.2 is a candidate tumor suppressor gene that has a diadenosine triphosphate (Ap3A) hydrolase activity, but its role in carcinogenesis remains uncertain. To investigate the role of FHIT in normal cells, specific polyclonal antibodies to recombinant rat FHIT protein were generated. Immunoblot analysis revealed the 17-kd FHIT protein was most abundantly expressed in kidney and liver, whereas heart, skeletal muscle, and adrenal gland expressed trace amounts. In kidney, immunohistochemical staining was strongly observed in distal convoluted tubule and collecting duct during postnatal growth period. By a nested reverse transcription-PCR analysis of FHIT from 2 human kidney cancer cell lines, four abnormal-sized FHIT transcripts, with deletion and/or insertion, were detected. These were derived from the results of exon skipping, and/or insertion of FHIT intron 5 sequence, or selection of cryptic splice site within the ...

The Korean Journal of Internal Medicine, 2007

Background : Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat... more Background : Pulmonary damage resulting from lipid peroxidation is a principal effect of paraquat intoxication. The host-defense functions of surfactant are known to be mediated by the surfactant proteins A and D (SP-A and SP-D, respectively). The primary objective of this study was to evaluate the variations over time in levels of surfactant protein and lipid peroxidation (LPO) in lung tissue following free-radical-induced injury. Methods : 42 adult, male, Sprague-Dawley rats were administered intraperitoneal injections of paraquat (35 mg/kg body weight). SPA and SP-D levels were determined via Western blot. LPO in the left lung homogenate was measured via analyses of the levels of thiobarbituric acid-reactive substances. Results : LPO levels peaked at 6 hours, with no associated histological changes. SP-D levels increased until hour 12 and declined until hour 48; SP-D levels subsequently began to increase again, peaking at hour 72. SPA levels peaked at hour 6, declining thereafter. Conclusions : We suggest that in the early phase of paraquat injury, SP-D levels reflect alveolar damage and that de novo synthesis of SP-D takes 72 hours. Levels of SPA , on the other hand, reflect abnormalities in the surfactant system in the late stage of paraquat intoxication. Surfactant proteins may play a role in protecting the lungs from reactive oxygen injury. A time-dependent variation has been observed in the levels of surfactant proteins A and D following paraquat injury, and it has been suggested that these proteins play a role in the protection of lung tissue against ROS-induced injuries.

Research communications in molecular pathology and pharmacology, 2002

Alterations of the FHIT gene occur as frequent events in several human cancers. Replacement of ex... more Alterations of the FHIT gene occur as frequent events in several human cancers. Replacement of exogenous wild-type FHIT gene has been shown to induce suppression of tumorigenicity of human FHIT-negative cells in nude mice and aberrant FHIT transcripts have been observed in a variety of human solid tumors. In the presence study, we performed a nested reverse transcription-polymerase chain reaction (RT-PCR) analysis to identify aberrant FHIT transcripts in 6 gastric cancer cell lines. In addition to the wild-type FHIT transcript, small-sized transcripts with various number and lengths were observed in all of the cell lines examined. Sequence analysis confirmed that different types of truncated transcripts included exonic deletions, insertions of intron 5 sequences between exons, and combinations of both. Most of these transcripts lacked exon 5 in which translation initiation codon is located. Aberrant transcripts with partial exonic deletions, resulting from activation of cryptic spli...

International journal of molecular medicine, 2012

Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits p... more Juglone (5-hydroxy-1,4-naphthalenedione) from black walnut trees induces apoptosis and inhibits proliferation of various malignant cells. Here, we investigated whether juglone affects 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced cell transformation through the phosphoinositol 3-kinase (PI3K) pathway. The results showed that TPA- and endothelial growth factor (EGF)-induced anchorage-independent colony formation were suppressed in a dose-dependent manner by treatment of JB6 CI41 mouse skin epidermal cells with juglone (2.5 and 5 µM). We demonstrated that juglone suppressed PI3K activity via direct binding to PI3K by sepharose 4B pull-down assay and western blot analysis. Juglone significantly suppressed TPA-induced protein kinase B (AKT) and c-Jun phosphorylation and c-fos activation, but not mitogen-activated protein-kinase kinase (MEK), extracellular signaling-regulated kinase (ERK) or 90 kDa ribosomal protein S6 kinase (RSK) phosphorylation. Juglone significantly blocked acti...

Molecular Medicine Reports, 2012

a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a de... more a disintegrin and metalloproteinase (ADAM) with thrombospondin type 1 motif 12 (ADAMTS12) is a degradative enzyme that interacts with the degradable fragments of cartilage oligomeric matrix protein, which is a prominent non-collagenous matrix component in articular cartilage. ADAMTS12 has been observed in the cartilage, synovial fluid and serum of arthritic patients, and may play an important role in the pathogenesis of arthritis. In the present study, we investigated whether genetic polymorphisms of ADAMTS12 are associated with rheumatoid arthritis (RA). To observe the association between ADAMTS12 and RA, we genotyped three single nucleotide polymorphisms (SNPs) (rs1364044, intron C/T; rs10461703, intron C/T; rs25754, missense Thr1495Ile) of ADAMTS12 using a direct sequencing method in 303 RA patients and 495 control subjects. Multiple logistic regression models were performed to analyze the genetic data. SNPStats and SNPAnalyzer Pro programs were used to estimate the odds ratios, 95% confidence intervals and p-values. Bonferroni's correction (p c) was conducted to obtain a defined result. Of the three SNPs, the genotype frequency of rs10461703 was associated with the development of RA (p c =0.0024 in the co-dominant model; p c =0.0009 in the dominant model; p c =0.0006 in the log-additive model). The allele frequency of rs10461703 also showed a significant difference between RA and controls (p c <0.0001). The C allele frequency of rs10461703 was lower in the RA group (36.6%) compared to the control group (45.7%), whereas the T allele frequency of rs10461703 in the RA group (63.4%) was higher compared to that in the control group (54.3%). The other two SNPs (rs1364044 and rs25754) were not associated with the development of RA. However, we did not find any association between the three tested SNPs and RA patients according to clinical features, including erythrocyte sedimentation rate, C-reactive protein level, rheumatoid factor (+ and-) and bone erosion (+ and-). Our results suggest that ADAMTS12 may be a susceptibility gene for RA development.

Molecular and Cellular Biochemistry, 2012

Post-translational modification of peptidyl cis/ trans prolyl isomerase Pin1 is crucial in regula... more Post-translational modification of peptidyl cis/ trans prolyl isomerase Pin1 is crucial in regulation of gene stability. Pin1 phosphorylation at Ser 16 has been regarded as a marker for Pin1 isomerase activity and introduction of phosphorylation on Ser/Thr-Pro of substrate proteins is prerequisite for its binding activity with Pin1 and subsequent isomerization. Here, we found that 90 kDa ribosomal protein S6 kinase 2 (RSK2) could form a physical complex with Pin1, leading to phosphorylation of Pin1 at Ser 16 ex vivo and in vitro respectively. Intriguingly, Pin1 ?/? mouse embryonic fibroblasts (MEFs) exhibited significantly an increase in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced RSK2 phosphorylation with a marginal Pin1 phosphorylation compared with Pin1-/-MEFs. Moreover, TPA-induced Ser 16 Pin1 phosphorylation as well as RSK2 phosphorylation was considerably profound in RSK ?/? MEFs but not in RSK-/-MEFs. Consequently, knockdown of Pin1 using shRNA-Pin1 suppressed TPAinduced cell transformation in JB6 CI41 cells. Overall, these results indicate that Pin1 plays a critical role in TPA-induced tumorigenesis plausibly via physical interaction with RSK2 and reciprocal phosphorylation, therefore suggesting a potential therapeutic target for cancer treatment. Keywords Ribosomal S6 kinase 2 Á Peptidyl cis/trans prolyl isomerase Á Tumorigenesis Á 12-O-tetradecanoylphorbol-13-acetate Á Post-translational modification Abbreviations Pin1 Peptidyl-prolyl cis/trans isomerase RSK2 90 kDa ribosomal protein S6 kinase 2 MEFs Mouse embryonic fibroblasts TPA 12-O-tetradecanoylphorbol-13-acetate ERK Extracellular signal-regulated kinase MEK Mitogen-activated protein kinase

Experimental & Molecular Medicine, 1998

Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubat... more Treatment with certain DNA-damaging agents induce a complex cellular response comprising pertubation of cell cycle progression and/or apoptosis on proliferating mammalian cells. Our studies were focused on the cellular effects of nickel (II) acetate, DNAdamaging agent, on Chinese hamster ovary (CHO) cells. Fragmented DNAs were examined by agarose gel electrophoresis and cell cycle was determined by DNA flow cytometry using propidium iodide fluorescence. Apparent DNA laddering was observed in cells treated with 240 M nickel (II) and increased with a concentration-dependent manner. Tr e a t m e n t of nickel (II) acetate resulted in apoptosis which was accompanied by G 2 /M cell accumulation. Proportion of CHO cells in G 2 /M phase was also significantly increased in cells exposed to at least 480 M nickel (II) from 57.7% of cells in the G 0 / G 1 phase, 34.7% in the S phase, and 7.6 % in the G 2 /M phase for 0 M nickel (II), to 58.6%, 14.5%, and 26.9% for 640 M nickel (II). These findings suggest that nickel (II) can modulate cellular response through some common effectors involving in both apoptotic and cell cycle regulatory pathways.

Biochemical and Biophysical Research Communications, 2001

Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric... more Genomic alterations and abnormal expression of the fragile histidine triad (FHIT) gene in gastric carcinomas were examined to determine whether the FHIT gene is actually a frequent target for alteration during gastric carcinogenesis. To correlate DNA and RNA lesions of the FHIT gene with the effect on FHIT protein expression, we have investigated the FHIT gene for loss of heterozygosity (LOH), aberrant transcripts, point mutations, and protein expression in 35 gastric adenocarcinomas. Allelic loss at D3S1300 was detected in 7 of 33 (21%) informative cases. Aberrant transcripts, with deletions and/or insertions, were observed in 20 of 35 (57.1%) cases and resulted from alternative splicing through exon skipping and/or insertion of the FHIT intron 5 sequence or activation of the cryptic splice site. Point mutations were not found in the FHIT coding region but detected in noncoding exon 2, 3, 4, or 5 of eight aberrant transcripts. Significant reduction of FHIT protein expression was observed in 22 of 35 (62.9%) cases. Aberrant FHIT transcription was shown to be associated with loss of FHIT protein expression. However, aberrant FHIT transcripts themselves were not associated with any clinicopathological parameters, such as age, sex, tumor site, or clinical stage. Moreover, there was no association between the presence of LOH at D3S1300 and the expression of aberrant FHIT transcripts. Nevertheless, high frequency of aberrant FHIT transcripts, significant rate of LOH at D3S1300, and altered expression of the FHIT protein indicate that alterations of the FHIT gene can play an important role in gastric carcinogenesis.

Research communications in molecular pathology and pharmacology, 2002

The fragile histidine triad (FHIT) gene located in human chromosome 3p14.2 is a candidate tumor s... more The fragile histidine triad (FHIT) gene located in human chromosome 3p14.2 is a candidate tumor suppressor gene that has a diadenosine triphosphate (Ap3A) hydrolase activity, but its role in carcinogenesis remains uncertain. To investigate the role of FHIT in normal cells, specific polyclonal antibodies to recombinant rat FHIT protein were generated. Immunoblot analysis revealed the 17-kd FHIT protein was most abundantly expressed in kidney and liver, whereas heart, skeletal muscle, and adrenal gland expressed trace amounts. In kidney, immunohistochemical staining was strongly observed in distal convoluted tubule and collecting duct during postnatal growth period. By a nested reverse transcription-PCR analysis of FHIT from 2 human kidney cancer cell lines, four abnormal-sized FHIT transcripts, with deletion and/or insertion, were detected. These were derived from the results of exon skipping, and/or insertion of FHIT intron 5 sequence, or selection of cryptic splice site within the ...