• Biomolecules & Therapeutics
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• v.26 no.3
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• pp.298-305
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• 2018

Rhomboid family member 2 gene (Rhbdf2) is an inactive homologue lacking essential catalytic residues of rhomboid intramembrane serine proteases. The protein is necessary for maturation of tumor necrosis factor-alpha ($TNF-{\alpha}$) converting enzyme, which is the molecule responsible for the release of $TNF-{\alpha}$. In this study, Rhbdf2 knockout (KO) mice were produced by CRISPR/CAS9. To see the effects of the failure of $TNF-{\alpha}$ release induced by Rhbdf2 gene KO, collagen-induced arthritis (CIA), which is the representative $TNF-{\alpha}$ related disease, was induced in the Rhbdf2 mutant mouse using chicken collagen type II. The severity of the CIA was measured by traditional clinical scores and histopathological analysis of hind limb joints. A rota-rod test and grip strength test were employed to evaluate the severity of CIA based on losses of physical functions. The results indicated that Rhbdf2 mutant mice showed clear alleviation of the clinical severity of CIA as demonstrated by the significantly lower severity indexes. Moreover, a grip strength test was shown to be useful for the evaluation of physical functional losses by CIA. Overall, the results showed that the Rhbdf2 gene has a significant effect on the induction of CIA, which is related to $TNF-{\alpha}$.

• Journal of Life Science
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• v.20 no.10
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• pp.1476-1482
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• 2010

The purpose of the present investigation was to evaluate the effects of swimming training on response of lipid peroxide (MDA) and superoxide dismutase (SOD) enzyme activity of hyperlipidemic rats. Twenty-five male SD rats (6 weeks old) were randomly divided into a control group and 4 swimming groups after hyperlipidemia induction for 4 weeks through a 1% cholesterol diet. Swimming groups were then divided into unloaded swimming group, low-loaded swimming group, moderate-loaded swimming group and high-loaded swimming group by swimming intensity, and made to swim for 6 weeks (6 days/week). The loaded swimming group rats among the swimming groups swam a lead weight equivalent to 0%, 3%, 5% and 7% of body weight attached to the base of the tail. All data were expressed as mean and standard deviation by using an SPSS/$PC^+$ program, and to evaluate the differences between groups, data were analyzed by one-way analysis of variance and Duncan multiple range test (${\alpha}$=0.05) was performed to test the significant levels of differences between groups. The conclusions obtained from this study were as follows: 1) all swimming groups had significantly lower levels of MDA than the control group (p<0.001). Among the swimming groups, the moderate-loaded group had a significantly lower level than the unloaded group, low-loaded group and high-loaded group (p<0.001). 2) all swimming groups had significantly higher levels of SOD than the control group (p<0.01). Among swimming groups, the unloaded group, moderate-loaded group and high-loaded group had significantly higher levels than the low-loaded group (p<0.01).

• Journal of Life Science
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• v.30 no.5
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• pp.483-490
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• 2020

The ubiquitin system uses ligases and deubiquitinases (DUBs) to regulate ubiquitin position on protein substrates and is involved in many biological processes which determine stability, activity, and interaction of the target substrate. DUBs are classified in six groups according to catalytic domain, namely ubiquitin-specific proteases (USPs); ubiquitin C-terminal hydrolases (UCHs); ovarian tumor proteases (OTUs); Machado Joseph Disease proteases (MJDs); motif interacting with Ub (MIU)-containing novel DUB family (MINDY); and Jab1/MPN/MOV34 metalloenzymes (JAMMs). Otubain 1 (OTUB1) is a DUB in the OTU family which possesses both canonical and non-canonical activity and can regulate multiple cellular signaling pathways. In this review, we describe the function of OTUB1 through regulation of its canonical and non-canonical activities in multiple specifically cancer-associated pathways. The canonical activity of OTUB1 inhibits protein ubiquitination by cleaving Lys48 linkages while its non-canonical activity prevents ubiquitin transfer onto target proteins through binding to E2-conjugating enzymes, resulting in the induction of protein deubiquitination. OTUB1 can therefore canonically and non-canonically promote tumor cell proliferation, invasion, and drug resistance through regulating FOXM1, ERα, KRAS, p53, and mTORC1. Moreover, clinical research has demonstrated that OTUB1 overexpresses with high metastasis in many tumor types including breast, ovarian, esophageal squamous, and glioma. Therefore, OTUB1 has been suggested as a diagnosis marker and potential therapeutic target for oncotherapy.

• Toxicological Research
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• v.24 no.4
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• pp.263-271
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• 2008

Recently we reported that 2-bromopropane (2-BP) has maternal toxicity, embryotoxicity, and teratogenicity in Sprague-Dawley rats. The aims of this study are to examine the potential effects of 2-BP administration on pregnant dams and embryo-fetal development, and to investigate the effects of metabolic activation induced by phenobarbital (PB) on developmental toxicities of 2-BP. Pregnant rats received 1000 mg/kg/day subcutaneous 2-BP injections on gestational days (GD) 6 through 10 (Group II and Group IIII) or 11 through 15 (Group IV). Pregnant rats in Group III received an intraperitoneal PB injection once daily at 80 mg/kg/day on GD 3 through 5 for induction of the liver metabolic enzyme system. Control rats received vehicle injections only on GD 6 through 15. All dams underwent caesarean sections on GD 20 and their fetuses were examined for external, visceral, and skeletal abnormalities. Significant adverse effects on pregnant dams and embryo-fetal development were observed in all the treatment groups, and the maternal and embryo-fetal effects of 2-BP observed in Group II were higher than those seen in Group IV. Conversely, maternal and embryo-fetal developmental toxicities observed in Group III were comparable to those seen in Group II. These results suggest that the potential effects of 2-BP on pregnant dams and embryo-fetal development are more likely in the first half of organogenesis (days $6{\sim}10$ of pregnancy) than in the second half and that the metabolic activation induced by PB pre-treatment did not modify the developmental toxic effects of 2-BP in rats.

• Herbal Formula Science
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• v.25 no.1
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• pp.51-68
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• 2017

Objectives : Oxidative stress due to excessive accumulation of reactive oxygen species (ROS) is one of the risk factors for the development of several chronic diseases, including neurodegenerative diseases. Methods : In the present study, we investigated the protective effects of cheongnoemyeongsin-hwan (CNMSH) against oxidative stress‑induced cellular damage and elucidated the underlying mechanisms in neuronal-derived SH-SY5Y cells. Results : Our results revealed that treatment with CNMSH prior to hydrogen peroxide (H2O2) exposure significantly increased the SH-SY5Y cell viability, indicating that the exposure of the SH-SY5Y cells to CNMSH conferred a protective effect against oxidative stress. CNMSH also effectively attenuated H2O2‑induced comet tail formation, and decreased the phosphorylation levels of the histone ${\gamma}H2AX$, as well as the number of apoptotic bodies and Annexin V‑positive cells. In addition, CNMSH exhibited scavenging activity against intracellular ROS generation and restored the mitochondria membrane potential (MMP) loss that were induced by H2O2, suggesting that CNMSH prevents H2O2‑induced DNA damage and cell apoptosis. Moreover, H2O2 enhanced the cleavage of caspase-3 and degradation of poly (ADP-ribose)-polymerase, a typical substrate protein of activated caspase-3, as well as DNA fragmentation; however, these events were almost totally reversed by pretreatment with CNMSH. Furthermore, CNMSH increased the levels of heme oxygenase-1 (HO-1), which is a potent antioxidant enzyme, associated with the induction of nuclear factor-erythroid 2-related factor 2 (Nrf2). According to our data, CNMSH is able to protect SH-SY5Y cells from H2O2-induced apoptosis throughout blocking cellular damage related to oxidative stress through a mechanism that would affect ROS elimination and activating Nrf2/HO-1 signaling pathway. Conclusions : Therefore, we believed that CNMSH may potentially serve as an agent for the treatment and prevention of neurodegenerative diseases caused by oxidative stress.

• Journal of the Korean Society of Food Science and Nutrition
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• v.17 no.4
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• pp.376-383
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• 1988

The effect of dietary methionine level on lipid peroxidation of rats was studied. Rats were fed vitamin E- selenium- deficient diet or diet supplemented with various levels (0.3, 0.6, 0.9%) of methionine. In rat fed MF diet, body weight gain and feed efficiency ratio were decreased compared with those of control rats, but reversed by supplementation with 0.3 and 0.6% methionine. Lipid peroxide levels in plasma and hepatic mitochondrial fraction of MF group rats were significantly higher than those of control rats. However, supplementation with 0.6% methionine modified this increment. GSH-Px activity was decrased to varying degrees in erythrocyte and hepatic mitochondrial fraction from rats fed MF diet. Methionine supplementation did not affect induction of this enzyme activity. Examination of hepatocytes by electronmicroscopy showed that Influence of vitamin E, selenium, and methionine deficiency was mainly characterized by lipid droplets, swollen mitochondria and microvilli destruction. Supplementation with various levels of dietary methionine modified these changes to some extent. The results of this experiment indicated that MF diet causes significant change in lipid peroxide level, GSH-Px activity and morphology of rats which these changes may lessen by supplementation with 0.6% methionine.

• Asian Pacific Journal of Cancer Prevention
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• v.15 no.24
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• pp.10879-10882
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• 2015

Objective: To investigate the effect of intraoperative glucose fluctuation and postoperative interlukin-6 (IL-6), tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), C-reactive protein (CRP) levels on the short-term prognosis of patients with intracranial supratentorial neoplasms. Materials and Methods: Eighty-six patients undergoing intracranial excision were selected in The Second Hospital of Jilin University. According to the condition of glucose fluctuation, the patients were divided into group A (glucose fluctuation <2.2 mmol/L, n=57) and group B (glucose fluctuation ${\geq}2.2mmol/L$, n=29). Glucose was assessed by drawing 2 mL blood from internal jugular vein in two groups in the following time points, namely fasting blood glucose 1 d before operation ($T_0$), 5 min after anesthesia induction ($T_1$), intraoperative peak glucose ($T_2$), intraoperative lowest glucose ($T_3$), 5 min after closing the skull ($T_4$), immediately after returning to intensive care unit (ICU) ($T_5$) and 2 h after returning to ICU ($T_6$). 1 d before operation and 1, 3 and 6 d after operation, serum IL-6 and TNF-${\alpha}$ levels were detected with enzyme-linked immunosorbent assay (ELISA), and CRP level with immunoturbidimetry. Additionally, postoperative adverse reactions were monitored. Results: There was no statistical significance between two groups regarding the operation time, anesthesia time, amount of intraoperative bleeding and blood transfusion (P>0.05). The glucose levels in both groups at $T_1{\sim}T_6$ went up conspicuously compared with that at $T_0$ (P<0.01), and those in group B at $T_2$, $T_4$, $T_5$ and $T_6$ were significantly higher than in group A (P<0.01). Serum IL-6, TNF-${\alpha}$ and CRP levels in both groups 1, 3 and 6 d after operation increased markedly compared with 1 d before operation (P<0.01), but the increased range in group A was notably lower than in group B (P<0.05 or P<0.01). Postoperative incidences of hypoglycemia, hyperglycemia and myocardial ischemia in group A were significantly lower than in group B (P<0.05), and respiratory support time obviously shorter than in group B (P<0.01). Conclusions: The glucose fluctuation of patients undergoing intracranial excision is related to postoperative IL-6, TNF-${\alpha}$ and CRP levels and those with small range of glucose fluctuation have better prognosis.

• Research in Plant Disease
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• v.12 no.1
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• pp.40-45
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• 2006

The plant defence activator, Acibenzolar-S-methyl [benzo (1,2,3) thiadiazole-7-carbothioic acid-S-methyl ester, ASM] was assayed on tomato seedlings for its ability to induce resistance against Botrytis cinerea, the causal agent of gray mold in tomato. Pre-treatment of plants with ASM reduced the severity of the disease as well as the growth of the mycelium in plants. In ASM treated plants, reduction in disease severity (up to 55%) was correlated with suppression of mycelia growth (up to 46.5%) during the time course of infection. In plants treated with ASM, activities of peroxidase were determined as markers of resistance. Applications of ASM induced Progressive and significant increase of the enzyme in locally treated tissues. Such responses were expressed earlier and with a much higher magnitude when ASM-treated seedlings were challenged with the pathogen, thus providing support to the concept that a signal produced by the pathogen is essential for triggering enhanced synthesis and accumulation of the enzymes. No such activities were observed in water-treated control plants. Therefore, the slower symptom development and reduction in mycelium growth in ASM treated plants might be due to the increase in activity of oxidative and antioxidative protection systems in plants.

• The Korean Journal of Food And Nutrition
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• v.26 no.3
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• pp.485-491
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• 2013

Rhodiola spp. and red ginseng have been used for food and medicinal applications in disease chemoprevention in many Asian countries. Increased oxidative stress by reactive oxygen species (ROS) has been proposed to be a major cause of muscle fatigue. The present study was designed to investigate the protective effects of a fermented hot-water extract mixture from Rhodiola sachalinensis and red ginseng (MFR) on cell damage and the antioxidant enzyme system in $H_2O_2$-induced oxidative stress in skeletal muscle cells. C2C12 myoblasts were treated with various concentrations of NFR (non-fermented Rhodiola sachalinensis extract), FR (fermented hot-water extract from Rhodiola sachalinensis) and MFR for up to 5 days after the standard induction of differentiation, followed by semi-quantitative RT-PCR. MFR treatment dose-dependently protected oxidative damage of C2C12 cells. The treatment with MFR also enhanced mRNA expressions of MyoD, Cu/Zn SOD, Mn-SOD and GPX up to 16%. These results indicate that MFR exerts an anti-oxidative effect through a mechanism (s) that may involve the up-regulation of antioxidant enzymes, which may be important for the cellular redox environment in muscle cells.

• Applied Biological Chemistry
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• v.34 no.2
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• pp.162-167
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• 1991

In an attempt to explore the mechanistic aspects of chilling injury in plants and their defensive measures against the low temperature stress, the time sequential measurements of pyruvate, superoxide radicals$(O_{\overline{2}})$ and antioxygenic enzymes during whole period of injury-inducing treatment were performed using mostly rice seedlings. Pyruvate was substantialy accumulated in leaf tissues during the exposure period to $5^{\circ}C$ of the seedlings ; the relative extent of the accumulation was increased with increasing time of the cold treatment. When the cold-treated plants were translocated to ambient temperature$({\sim}25^{\circ}C)$, the accumulation started to dissipate, concomitantly accompaning a remarkable increase in the $O_{\overline{2}}$ level of tissues. Superoxide dismutase(SOD) and catalase were also activated during post-chilling period, although they showed a considerable lag time for activation. In contrast, glutathione peroxidase, another antioxygenic enzyme in cells, was not activated at all by preceding cold treatment of plants. The uptake of exogenous $O_{\overline{2}}$ by the roots of rice seedlings resulted in increase in the activities of SOD and catalase in root tissues. The supply of $H_2O_2$ to plan st brought about the activation of catalase in situ, while failing to exert any effect on the activation state of glutathione peroxidase. The results obtained in this work suggest that pyruvate accumulation in cells is the direct cause of the overproduction of $O_{\overline{2}}$ and thereby other toxic activated oxygen species, and that SOD and catalase may play a crucial role in the protection of plant cells against active oxygen-mediated chilling injury.