• BMB Reports
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• 제50권7호
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• pp.379-383
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• 2017

We previously reported that p53 plays a role as a key regulator in the tetraploid G1 checkpoint, which is activated by actin damage-induced cytokinesis blockade and then prevents uncoupled DNA replication and nuclear division without cytokinesis. In this study, we investigated a role of Skp2, which targets CDK2 inhibitor p27/Kip1, in actin damage-induced tetraploid G1 arrest. Expression of Skp2 was reduced, but p27/Kip1 was increased, after actin damage-induced cytokinesis blockade. The role of Skp2 repression in tetraploid G1 arrest was investigated by analyzing the effects of ectopic expression of Skp2. After actin damage, ectopic expression of Skp2 resulted in DNA synthesis and accumulation of multinucleated cells, and ultimately, induction of apoptosis. These results suggest that Skp2 repression is important for sustaining tetraploid G1 arrest after cytokinesis blockade and is required to prevent uncoupled DNA replication and nuclear division without cytokinesis.

• Animal cells and systems
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• 제13권4호
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• pp.405-409
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• 2009

When DNA double-strand breaks (DSBs) were induced in mammalian cells, many DNA damage response proteins are accumulated at damage sites to form nuclear foci called IR-induced foci. Although the formation of foci has been shown to promote repair efficiency, the structural organization of chromatin in foci remains obscure. BAF53 is an actin-related protein which is required for maintenance of chromosome territory. In this study, we show that the formation of IR-induced foci by $\gamma$-H2AX and 53BP1 were reduced when BAF53 is depleted, while DSB- activated ATM pathway and the phosphorylation of H2AX remains intact after DNA damage in BAF53 knockdown cells. We also found that DSB repair efficiency was largely compromised in BAF53 knockdown cells. These results indicate that BAF53 is critical for formation of foci by $\gamma$-H2AX decorated chromatin at damage sites and the structural organization of chromatin in foci is an important factor to achieve the maximum efficiency of DNA repair.

• Toxicological Research
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• 제14권4호
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• pp.577-585
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• 1998

Cadmium is an important industrial and environmental pollutant and has adverse effects on cell growth and metabolism, although the mechanisms of its cellular toxicity are still unclear. This study was performed to elucidate the cytotoxic mechanism of cadmium in the viewpoint of oxidative stress and cytoskeleton alterations in WB-F344 rat liver epithelial cells. 200 $\mu\textrm{M}$ $CdCl_2$ caused a severe disassembling of microtubule and micro filament and an apparent cell retraction under an observation with fluorescence micoscope. (equation omitted)-tubulin and F-actin protein were highly thiolated at 20 min and then disappeared from 1 hour after the treatment of 200 $\mu$M CdCl$_2$in the immunoblot analysis. Intracellular GSH was decreased from 1hr to 24 hrs by 66.6 or 200 $\mu\textrm{M}$ of $CdCl_2$. Intracellular protein thiol was also decreased by 22.2, 66.6 and 200 $\mu\textrm{M}$ of $CdCl_2$ at 1 hour after its treatment. The product of lipid peroxidation (malondialdehyde) was increased from 4 hrs by 66.6 and 200$\mu\textrm{M}$ of $CdCl_2$. These data indicate that cadmium induces oxidative stress involving disassembling of microtubule and micro filament, thiolation of (equation omitted)-tubulin and actin protein, depletion of GSH and protein thiol, and increase of lipid peroxidation.

• The Korean Journal of Physiology and Pharmacology
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• 제27권3호
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• pp.209-220
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• 2023

This study is to determine the regulation of nitric oxide synthase 3 (NOS3) by edaravone in mice with hypoxic pulmonary hypertension (HPH). C57BL/6J mice were reared in a hypoxic chamber. HPH mice were treated with edaravone or edaravone + L-NMMA (a NOS inhibitor). Lung tissue was collected for histological assessment, apoptosis analysis, and detection of malondialdehyde, superoxide dismutase, tumor necrosis factor (TNF)-α, interleukin (IL)-6, and NOS3. The levels of serum TNF-α and IL-6 were also measured. Immunohistochemistry was used to visualize the expression of α-smooth muscle actin (SMA) in pulmonary arterioles. Edaravone treatment improved hemodynamics, inhibited right ventricular hypertrophy, increased NOS3 expression, and reduced pathological changes, pulmonary artery wall thickness, apoptotic pulmonary cells, oxidative stress, and the expression of TNF-α, IL-6, and α-SMA in HPH mice. L-NMMA treatment counteracted the lung protective effects of edaravone. In conclusion, edaravone might reduce lung damage in HPH mice by increasing the expression of NOS3.

• Anatomy and Cell Biology
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• 제56권1호
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• pp.109-121
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• 2023

Thioacetamide (TAA) exposure and hepatitis C virus infection are usually associated with renal dysfunction. Sofosbuvir (SFV) and daclatasvir (DAC) drugs combination has great value in the treatment of hepatitis C. The study aimed to identify the nephrotoxic effects of TAA and to evaluate the ameliorative role of SFV and DAC in this condition. Forty-eight adult male albino rats were divided into eight groups and received saline (control), SFV, DAC, SFV+DAC, TAA, TAA+SFV, TAA+DAC and TAA+SFV+DAC for eight weeks. Kidney and blood samples were retrieved and processed for histological (Hematoxylin and Eosin and Masson's trichrome), immunohistochemical (α-smooth muscle actin), and biochemical analysis (urea, creatinine, total protein, albumin, malondialdehyde, reduced glutathione, superoxide dismutase, and tumor necrosis factor-α). Examination revealed marked destruction of renal tubules on exposure to TAA with either hypertrophy or atrophy of glomeruli, increase in collagen deposition, and wide expression of α-smooth muscle actin. Also, significant disturbance in kidney functions, oxidative stress markers, and tumor necrosis factor-α. Supplementation with either SFV or DAC produced mild improvement in the tissue and laboratory markers. Moreover, the combination of both drugs greatly refined the pathology induced by TAA at the cellular and laboratory levels. However, there are still significant differences when compared to the control. In conclusion, SFV and DAC combination partially but greatly ameliorated the renal damage induced by TAA which might be enhanced with further supplementations to give new hope for those with nephropathy associated with hepatitis.

• Mycobiology
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• 제48권6호
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• pp.495-500
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• 2020

Leaf spot on lemon balm is frequently observed in Korea, causing considerable damage to crops. In 2014 and 2015, the occurrence of leaf spot was observed in several production greenhouses at Suwon, Gongju, and Namwon in Korea. Symptoms on lower leaves initially developed as small, distinct, discolored lesions, which enlarged progressively turning into dark brown, angular spots surrounded by purplish-brown margins. Based on the morphological characteristics and sequence analysis of actin (ACT), translation elongation factor 1-alpha (EF-1α), internal transcribed spacer (ITS), 28S nrDNA (LSU), and RNA polymerase II second largest subunit (RPB2), the fungus associated with the lemon balm leaf spot was determined as Septoria melissae. To the best of our knowledge, this is the first report of lemon balm leaf spot caused by S. melissae in Asia as well as in Korea.

• Toxicological Research
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• 제25권2호
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• pp.71-78
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• 2009

We investigated the pathogenesis of liver tissue damage during the lipid peroxidation and fibrogenesis with the observation of correlations between the parameters of collagen synthesis (and deposition) and lipid peroxidation in liver fibrosis (cirrhosis) rats. Rats were randomly divided into two groups, normal and $CCl_4$-thiopental sod. intoxicated group. And the one group was treated intragastrically with the mixture of $CCl_4$-thiopental sod. 3 times per week for 3 weeks. The liver tissue and sera were used for the measurement of hydroxyproline (HYP), malonedialdehyde (MDA) and superoxide dismutase (SOD). Biochemical parameters such as aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total-bilirubin and blood urea nitrogen (BUN) were measured. Additionally, the expression of collagen ${\alpha}1$(III) and $\beta$-actin mRNA was observed by RTPCR. The histological change in liver tissue was also observed by Masson's trichrome and H&E staining. Correlation analysis was carried by Spearman's rho method. All biochemical parameters except total-bilirubin were significantly higher in the $CCl_4$-thiopental sod. treated group than that of the normal group (p < 0.01). In the $CCl_4$-thiopental sod. treated group, Hyp as a parameter of collagen synthesis (deposition) and MDA as a metabolite of lipid peroxidation, were significantly elevated by 1.98 and 2.11 times higher than that of the normal group (p < 0.001) respectively. The activity of SOD in the $CCl_4$-thiopental sod. treated group is decreased significantly by 44.8% (p < 0.001). And collagen ${\alpha}1$(III) mRNA was more expressed in the $CCl_4$-thiopental sod. treated group than that of the normal group. However, the expression of $\beta$-actin mRNA is showed similar in both of groups. A good correlation was observed between the content of hyp and MDA concentration (r = 0.70, n = 40) in the two groups. And the correlation between the levels of hyp and SOD (r = -0.71, n = 25) is also reliable. However, no correlation were observed between MDA concentration and SOD (r = -0.40, n = 25) in the two groups. Elevated levels of MDA in $CCl_4$-thiopental sod. treated rats indicated enhancement of lipid peroxidation, which is accompanied by a decrease in SOD activity. Moreover, we could confirm that the parameters of collagen synthesis (and deposition) is in good correlation with the metabolite of lipid peroxidation (MDA) and the lipid peroxidation antagonizing enzyme (SOD). Hence, we propose that (1) lipid peroxidation and collagen synthesis (and deposition) could be enhanced by intragastrically application of $CCl_4$-thiopental sod. during a short terms. And (2) the intoxication of $CCl_4$-thiopental sod. could be used for monitoring of lipid peroxidation and collagen synthesis (and deposition) for test of antioxidant and antifibrotic agent.

• Radiation Oncology Journal
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• 제14권4호
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• pp.265-279
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• 1996

방사선은 DNA손상을 초래하고 세포 성장에 관련된 유전자의 발현 조절 및 apoptosis등을 유발한다고 알려져 있으며 본 연구는 신경계에 있어 방사선 조사 후 종양 발생율과 시간 경과의 관계 및 조사 양과 암 발생의 관계를 구명하기 위해 코발트 60의 전신조사에 따른 흰쥐 뇌 조직의 생체 반응을 연구하고자 하였다. 이를 위하여 상기조직의 jun 및 p53 유전자의 발현도를 1 Gy로 부터 100 Gy 범위의 감마선 용량별 및 1시간에서 6시간까지의 조사 훈 경과 시간 별로 Northern 분석하였다. Jun유전자 발현도는 ley이하에서 1시간 이내에 한계수준에 도달하였으며 30 Gy의 조사 1시간 째에 최대였다. 또한 조사 1시간 이후 1 Gy로부터 10 Gy 범위에서는 조사 5시간 및 6시간까지 점진적으로 증가되었으나 20 Gy로부터 100 Gy 범위에서는 조사 2시간까지 증가 후 감소되는 양상을 나타냈다. p53유전자의 발현도는 1 Gy이하에서 1시간 이내에 한계 수준에 근접했고 1 Gy의 조사 후 6시간 째에 최대였다. 1 Gy로부터 40 Gy까지의 범위에서는 조사 5시간 및 6시간까지 점진적으로 증가되는 반면 50 Gy에서 100 Gy범위에서는 조사 2시간 째까지 증가 후 감소되는 양상을 보였다. 따라서 감마선 조사양이 높을수록 jun 및 p53유전자는 신속하게 최대로 발현되었고 감마선 조사양이 낮을수록 서서히 증가되었다 그러나 jun유전자와 p53유전자의 감마선 조사에 따른 발현 양상에는 상호간의 연관성을 찾을 수 없었다.

• Journal of Acupuncture Research
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• 제33권3호
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• pp.29-43
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• 2016

Objectives : The purpose of this study was to investigate the effect of LR3 and SP6 acupuncture on liver damage of streptozotocin-induced diabetic mice. Methods : Male ICR mice were divided into four groups, consisting of the normal mice group(N), acupuncture-free diabetic mice group(Con), LR3-acupuncture diabetic mice group(LR3) and SP6-acupuncture diabetic mice group(SP6). The following measurements were taken: Body weight, food intake and water intake for 2 weeks; liver weight, and glucose levels in the serum and liver; ALT and AST in the serum; reactive oxygen species(ROS), reduced glutathione(GSH) and oxidized glutathione(GSSG) in the liver; and lastly, receptor for advanced glycation endproducts( RAGE), $N{\varepsilon}-carboxymethyl$ lysine(CML), $N{\varepsilon}-carboxyethyl$ lysine(CEL), phosphorylation of inhibitory kappa B alpha($p-I{\kappa}B{\alpha}$), nuclear factor-kappa B($NF-{\kappa}B$), activator protein-1(AP-1), cyclooxygenase-2(COX-2), inducible nitric oxide synthase(iNOS), tumor necrosis factor-alpha($TNF-{\alpha}$), ${\beta}-actin$, cytochrome c and caspase in the liver. Results : The liver weight and GSH/GSSG ratio were significantly increased in SP6 compared to Con. The glucose levels in the liver were significantly decreased in LR3 compared to Con. The generation of ROS and GSSG were significantly decreased in SP6 compared to Con. The expressions of RAGE, CML, AP-1, $TNF-{\alpha}$, cytochrome c and caspase 3 were significantly decreased in LR3 compared to Con. The expressions of $p-I{\kappa}B{\alpha}$, $NF-{\kappa}B$, AP-1, COX-2, iNOS and caspase 3 were significantly decreased in SP6 compared to Con. Conclusion : It is predicted that LR3 acupuncture is related to reduced glucose levels in the liver and expressions of AGE, and that, SP6 acupuncture is related to reduced oxidative stress-related transcription factors and inflammation-related proteins. Therefore, we suggest that LR3 and SP6 acupuncture have protective effects on the liver of streptozotocin-induced diabetic mice by preventing apoptosis.

• 대한한방내과학회지
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• 제29권1호
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• pp.200-218
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• 2008

Objectives : The purpose of this study was to investigate the effects of Injinchunggan-tang (Yinchenchinggan-tang) on DMN-induced liver damage by applying proteomics. Materials and Methods : Sprague-Dawley rats were used in this experiment and were divided into the normal group (normal saline), the control group (DMN) and the sample group (DMN+IJCGT). DMN was injected i.p. once a day three times a week for 3 weeks in the control group. Normal saline instead of DMN was administered to the normal group. In the sample group, Injinchunggan-tang (Yinchenchinggan-tang) extract was orally administered once a day for 10 days after DMN was induced. The livers of each group were processed and analyzed by histology, Western blot, $Oxyblot^{TM}$, CBB and 2-dimensional electrophoresis. Results : In the histological findings of the liver, IJCGT reduced collagen deposition and liver damage in DMN-induced hepatic fibrosis. IJCGT increased MMP-13 protein production assessed by western blot. Protein oxidation induced by DMN treatment was decreased by IJCGT. In the 2-dimensional electrophoresis finding, the level of the increased proteins induced by DMN treatment such as GRP 75, 58kDa glucose regulated protein and heat shock 70kDa protein 5 were decreased by IJCGT. IJCGT was considered to have the protective effects on hepatotoxicity induced by DMN. In the 2-dimensional electrophoresis finding, the level of increased oxidized proteins such as heat shock 70 protein, mitochondrial malonyltransferase, calreticulin precursor, actin, NADP-isocitrate dehydrogenase, ankyrin repeat and SOCS box protein 11 were decreased by IJCGT. IJCGT was considered to have protective effect on the protein production induced by DMN treatment. Conclusion : Injinchunggan-tang (Yinchenchinggan-tang) exerts an inhibitory effect against the fibrosis and protein oxidation induced by DMN treatment in the rat liver. IJCGT was considered to have protective effects on the hepatotoxicity and protein production induced by DMN treatment.