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Young Rok Seo - One of the best experts on this subject based on the ideXlab platform.
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Abstract LB-178: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair
Cancer Research, 2012Co-Authors: Young Rok SeoAbstract:Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the Cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53 wild type Cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53 wild-type RKO Cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating Cell Nucleus Antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated Cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild-type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr LB-178. doi:1538-7445.AM2012-LB-178
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Abstract B73: A novel chemopreventive molecular mechanism of selenium: p53-mediated DNA repair
Cancer Prevention Research, 2011Co-Authors: Young Rok SeoAbstract:Selenium is an essential trace element which has been considered as chemopreventive agent against cancer, due to its antioxidant activity. Among several selenium compounds, selenomethionine (SeMet) has significant protective effect toward various genotoxic stresses via stimulating DNA repair process. However, its mechanism is still not well elucidated. In this study, we examined the mechanism of SeMet in terms of p53-mediated base excision repair (BER). Our data showed that the amount of DNA damage was rapidly decreased in the presence of SeMet when methyl methanesulfonate (MMS), a BER-inducing agent, was treated in the Cells. In addition, the removal of apurinic/apyrimidinic sites was significantly enhanced in p53-wild type Cells in response to SeMet. Furthermore, we observed the Gadd45a, known to involve BER as one of the p53 downstream genes, was accumulated by SeMet in p53-wild type RKO Cells. Indeed the interaction of BER-mediated repair proteins including PCNA (proliferating Cell Nucleus Antigen) and APE/Ref-1 with Gadd45a was notably decreased by SeMet in p53 siRNA-treated Cells. In in vivo study, the frequency and size of polyp in AOM/DSS model as an animal model for colitis-related carcinogenesis was decreased in response to SeMet. Moreover, proteins related with DNA repair including Trx (thioredoxin), p53 and Gadd45a were increased in SeMet treated AOM/DSS model. Those results suggested that BER activity might be dependent on wild type p53 under the modulation of protein complexes with Gadd45a and repair protein including PCNA and APE/Ref-1 as a distinct chemopreventive mechanism of SeMet. Our study might provide an important evidence to develop the chemopreventive strategies against various oxidative stresses. Citation Information: Cancer Prev Res 2011;4(10 Suppl):B73.
Shi Suozhu - One of the best experts on this subject based on the ideXlab platform.
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Role of TIMP-1 expression in renal tubulointerstital lesion induced by unilateral ureteral obstruction
Chinese Journal of Nephrology, 2002Co-Authors: Shi SuozhuAbstract:Objective To explore the role of tissue inhibitor of metalloproteinase-1 (TIMP-1 )in the renal tubulointerstitial lesions induced by unilateral ureteral obstruction (UUO) . Methods Rats were sacrificed at 1, 3, 5, 7 and 14 days after UUO or sham-surgery. The protein expression of TIMP-1 ,α-smooth muscle actin(α-SMA) .proliferating Cell Nucleus Antigen (PCNA) and ED-1 in tubulointerstitium were detected by immunohistochemistry at each time point. Rusults TIMP-1 expression in renal tubulointerstitium increased progressively starting from 24 hours to day 14 post-ligation. TIMP-1 was mainly expressed in interstitial and some tubular Cells. On 24 hours post-ligation a few α-SMA-positive interstitial Cells and ED-1-positive macrophages were present. From day 3 the number of a-SMA-positive interstitial Cells and ED-1-positive macrophages increased. Some tubular epithelial Cells also expressed α-SMA. The renal tubulointersital expression of TIMP-1 was significantly associated with the relative volume of interstitium and the postive area of α-SMA. The expression of PCNA in tubular Cells peaked at day 3 after UUO, then decreased, but there were still many PCNA-positive interstitial Cells at day 7 and day 14. Conclusion TIMP-1 is active in interstitial and tubular Cells in the early phase of fibrotic process and may play an important role in mediating the tubulointerstital lesions after UUO.
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Role of type I plasminogen activator inhibitor in mediating renal tubulointerstitial injury of patients with IgA nephropathy
Chinese Journal of Nephrology, 2000Co-Authors: Shi SuozhuAbstract:Objective To explore the role of type 1 plasminogen activator inhibitor (PAI-1 ) in mediating renal tubulointerstitial injury of patients with IgA nephropathy. Methods The mRNA and protein production of PAI-l in renal tubulointerstitium were defected using in stiu hybridization and immunohistochemistry. Detections of Antigens of α-smooth muscle actin(α-SMA) and proliferating Cell Nucleus Antigen (PCNA) were also performed. Results PAI-l was normally expressed in the walls of vessels and distal tubules, but significantly increased in lesions of IgA nephropathy, including crescents, Bowman capsules and tubulointerstitial infiltrating Cells. There was lithe expression of PAl-1 in the glomerular capillary tufts. The renal expression of PAI-l was significantly correlated with serum creatinine (P 0. 01 ). PAI-1 expression was also positively correlated with the pathological parameters including tubulointerstitial infiltration, tubular atrophy and tubulointerstitial fibrosis(all P 0. 01). Besides, the renal expression of tubulointerstitial PAl-l was apparently correlated with those of α-SMA and PCNA. Conclusion PA-l may have an important role in mediating the tubulointerstitial fibrosis of IgA nephropathy.
Xiaoli Lan - One of the best experts on this subject based on the ideXlab platform.
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Uptake Kinetics of 99mTc-MAG3-Antisense Oligonucleotide to PCNA and Effect on Gene Expression in Vascular Smooth Muscle Cells
The Journal of Nuclear Medicine, 2005Co-Authors: Yan-rong Zhang, Yongxue Zhang, Wei Cao, Xiaoli LanAbstract:To investigate the feasibility of in vivo imaging study of atherosclerotic plaque and restenosis using antisense probe, we evaluated the uptake kinetics of radiolabeled oligonucleotides to the messenger RNA (mRNA) of proliferating Cell Nucleus Antigen (PCNA) in vascular smooth muscle Cells (VSMCs) and the effect on gene expression. Methods: The antisense oligonucleotide to PCNA was radiolabeled with 9 9 m Tc through bifunctional chelator mercaptoacetyltriglycine (MAG 3 ). The labeling efficiency was assessed by Sephadex G25 chromatography. The radiochemical purity, in vitro stability, and ability of the labeled antisense oligonucleotide to hybridize to its complement were analyzed by Sep-Pak C18 column chromatography. The uptake kinetics of 9 9 m Tc-labeled antisense oligonucleotide and sense oligonucleotide were studied in VSMCs in log and plateau phases. To study whether the antisense probe can hybridize to a respective sequence on the whole PCNA mRNA strand after radiolabeling, we performed reverse-transcriptase polymerase chain reaction to assay the PCNA mRNA level after the VSMCs had been incubated with the 9 9 m Tc-labeled antisense oligonucleotide and sense oligonucleotide. Results: The labeling efficiency of 9 9 m Tc-MAG 3 -antisense oligonucleotide was 60.1% (n = 5), the specific activity was 1,960 kBq/μg, and the radiochemical purity was more than 95% after purification. 9 9 m Tc-MAG 3 -antisense oligonucleotide was stable in vitro and retained the ability to hybridize with its complementary chain. Antisense oligonucleotide showed significantly higher accumulation than sense oligonucleotide in log phase, with peak values of 15.2% ′ 0.58% and 5.6% ′ 0.42%, respectively (P 0.05), but higher accumulation of antisense oligonucleotide was found in log phase than in plateau phase (P 0.05). The efflux of antisense oligonucleotide was obviously slower in log phase than in plateau phase (P < 0.05). Compared with 9 9 m Tc-MAG 3 -sense oligonucleotide, 9 9 m Tc-MAG 3 -antisense oligonucleotide could inhibit the expression of PCNA mRNA significantly. Conclusion: This in vitro study in VSMCs provided evidence that the 9 9 m Tc-labeled antisense oligonucleotide to PCNA can be used for in vivo imaging of atherosclerotic plaque and restenosis in further study.
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Oligonucleotide to PCNA and Effect on Gene Expression in Vascular Smooth Muscle Cells
2005Co-Authors: Yan-rong Zhang, Yongxue Zhang, Wei Cao, Xiaoli LanAbstract:To investigate the feasibility of in vivo imaging study of atherosclerotic plaque and restenosis using antisense probe, we evaluated the uptake kinetics of radiolabeled oligonucleotides to the messenger RNA (mRNA) of proliferating Cell Nucleus Antigen (PCNA) in vascular smooth muscle Cells (VSMCs) and the effect on gene expression. Methods: The antisense oligonucleotide to PCNA was radiolabeled with 99mTc through bifunctional chelator mercaptoacetyltriglycine (MAG3). The labeling efficiency was assessed by Sephadex G25 chromatography. The radiochemical purity, in vitro stability, and ability of the labeled antisense oligonucleotide to hybridize to its complement were analyzed by Sep-Pak C18 column chromatography. The uptake kinetics of 99mTc-labeled antisense oligonucleotide and sense oligonucleotide were studied in VSMCs in log and plateau phases. To study whether the antisense probe can hybridize to a respective sequence on the whole PCNA mRNA strand after radiolabeling, we performed reverse-transcriptase polymerase chain reaction to assay the PCNA mRNA level after the VSMCs had been incubated with the 99mTc-labeled antisense oligonucleotide and sense oligonucleotide. Results: The labeling efficiency of 99m TcMAG3-antisense oligonucleotide was 60.1% (n 5), the specific activity was 1,960 kBq/g, and the radiochemical purity was more than 95% after purification. 99mTc-MAG3-antisense oligonucleotide was stable in vitro and retained the ability to hybridize with its complementary chain. Antisense oligonucleotide showed significantly higher accumulation than sense oligonucleotide in log phase, with peak values of 15.2% 0.58% and 5.6% 0.42%, respectively (P 0.05). No significant difference was found between uptake of antisense oligonucleotide and uptake of sense oligonucleotide in plateau phase (P 0.05), but higher accumulation of antisense oligonucleotide was found in log phase than in plateau phase (P 0.05). The retention rate of antisense oligonucleotide in log phase was much higher than that of sense oligonucleotide (79.6% 0.96% vs. 59.8% 0.75%, P 0.05) at 240 min. The 2 probes did not significantly differ in plateau phase (P 0.05). The efflux of antisense oligonucleotide was obviously slower in log phase than in plateau phase (P 0.05). Compared with 99m Tc-MAG3sense oligonucleotide, 99mTc-MAG3-antisense oligonucleotide could inhibit the expression of PCNA mRNA significantly. Conclusion: This in vitro study in VSMCs provided evidence that the 99m Tc-labeled antisense oligonucleotide to PCNA can be used for in vivo imaging of atherosclerotic plaque and restenosis in further study.
Hongli Lin - One of the best experts on this subject based on the ideXlab platform.
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Effect of antisense-tissue inhibitor of metalloproteinase-1 gene transfer on tubulointerstitial lesion in rats with unilateral ureteral obstruction
National Medical Journal of China, 2002Co-Authors: Jianping Dong, Xiangmei Chen, Quanzhou Feng, Yue Tian, Zhaoxia Wang, Hongli LinAbstract:OBJECTIVE To observe the effect of antisense- human tissue inhibitor of metalloproteinase-1 (hTIMP-1) on tubulointerstitial lesion induced by unilateral ureteral obstruction (UUO). METHODS Forty-two SD rats, divided into 3 groups equally, underwent UUO and received intra-ureteral injection of normal saline, empty retroviral vectors and recombinant retroviral vectors containing antisense- hTIMP-1 respectively, and were sacrificed 3 and 7 days after the operation. The expression of antisense h-TIMP-1 in rat kidney was detected by RT-PCR. Immunohistochemistry was used to detect the expression of rat TIMP-1, alpha-SMA actin (alpha-SMA), and proliferating Cell Nucleus Antigen (PCNA) in tubulointerstitium. The relative area of renal tubulointerstitium was calculated. RESULTS The expression of antisense-hTIMP-1 mRNA was detected in rat renal tubulointerstitum. The expressions of rat TIMP-1, alpha-SMA and PCNA were lower in the obstructed kidneys of rats treated with antisense-hTIMP-1 than those in the rats in empty vectors group and normal saline group (3 day after: 0.75 +/- 0.07 vs 1.18 +/- 0.12, 1.14 +/- 0.14, P < 0.05; 7 days after: 2.02 +/- 0.16 vs 4.07 +/- 0.57, 4.13 +/- 0.60, P < 0.01). The relative area of renal tubulointerstitium in rats treated with antisense-hTIMP-1 was smaller than those in the empty vetors group and normal saline group (3 days after: 6.0 +/- 0.7 vs 8.2 +/- 1.2, 8.2 +/- 1.3, P < 0.01; 7 days after: 16.2 +/- 1.0 vs 21.2 +/- 2.6, 21.0 +/- 2.4, P < 0.01). More renal tubules were dilated, infiltration of inflammatory Cells was seen focally or diffusely, and the relative area of renal tubulointerstitium was smaller in the antisense-hTIMP-1 group than in the empty vectors group and normal saline group. No difference was seen among the degrees of dilation/atrophy of renal tubules and infiltration of inflammatory Cells in the three groups. No difference was seen between the relative area of renal tubulointerstitium in empty vectors group and normal saline group. CONCLUSION Antisense-hTIMP-1 may have beneficial effects on the tubulointerstitial lesion of obstructive nephropathy through inhibiting the expression of TIMP-1 in tubulointerstitum and the proliferation of interstitial and tubular Cells.
Lin Z - One of the best experts on this subject based on the ideXlab platform.
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Correlation between HSD17B4 expression in rat liver cancer tissues and inflammation or proliferation.
European Review for Medical and Pharmacological Sciences, 2018Co-Authors: Lin ZAbstract:OBJECTIVE Pathogenesis and progression of liver cancer are correlated with inflammatory response and estrogen level. 17β-estradiol dehydrogenase IV (HSD17B4) is highly expressed in human liver cancer tissues. HSD17B4 participates in liver cancer Cell proliferation via suppressing estradiol (E2) activity. This study generated a rat liver cancer model, on which the correlations between HSD17B4 and tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), proliferating Cell Nucleus Antigen (PCNA) expression were analyzed. MATERIALS AND METHODS Male Sprague Dawley (SD) rats were randomly assigned into control and model group (N=30). Diethylnitrosamine was used to induce liver cancer in a rat model. HE staining was used to observe liver injury whilst ELISA was used to measure serum TNF-α and IL-6 levels. The level of serum E2 was quantified by radioimmunoassay. Serum liver function indexes were measured by automatic biochemical analyzer. Protein expressions of HSD17B4, p-Akt, p-ERK and PCNA were measured by Western blot. RESULTS The inflammatory infiltration and necrosis of hepatocytes were shown in model group by HE staining, along with aggravated liver indexes. Significantly high phosphorylation level of Akt and ERK, along with the increase of HSD17B3 and PCNA expressions, was found in model group (p
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Relationships between intrahepatic metastasis of hepatoCellular carcinoma and in situ microenvironment, and the abundance of nm23-H1 H-ras mRNA
Chinese journal of oncology, 1998Co-Authors: Xiu-juan Zheng, Lin Z, Liu YAbstract:OBJECTIVE To reveal intrahepatic metastasis of hepatoCellular carcinoma (HCC) in relation to its micro-environment and nm23-H1 H-ras mRNA expression. METHODS In HCC specimens from 25 patients, the level of nm23-H1 and H-ras mRNA was examined by quantitative reverse transcription-polymerase chain reaction(RT-PCR). Tumor microvessel density(MDV), an essential factor of microenvironment and proliferating Cell Nucleus Antigen (PCNA), an index of tumor Cell proliferation, were also studied by immunohistochemical methods using antibodies against endothelial protein factor VIII-related Antigen(F8RA) and antibody PC-10. RESULTS The MDV and PCNA index in the group with intrahepatic metastasis were remarkably higher than those in the group without it (P < 0.01), while nm23-H1 mRNA expression level was negatively correlated with PCNA index (P < 0.05). The level of H-ras mRNA expression did not correlate with intrahepatic metastasis. MDV was positively correlated with PCNA index (P < 0.01). CONCLUSION Intrahepatic metastasis of HCC depends very much on its in situ microenvironment. The decline in nm23-H1 mRNA may implicate a preferential proliferation of nm23-negetive HCC Cells with highly metastastic potential which adapt well to the microenvironment.