• Journal of Life Science
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• v.19 no.7
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• pp.878-885
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• 2009

Serum ferritin levels are elevated in subjects with acute lung injury (ALI), and abnormalities in plasma and lung iron chemistry have also been demonstrated in ALI and acute respiratory distress syndrome (ARDS). Stress-inducible heme oxygenase-1 (HO-1), as well as ferritin, had shown anti-inflammatory actions. Biomarkers for early detection in patients who are likely to develop ARDS would give several therapeutic chances to the patients. In order to verify the predictability in severe hemorrhage-induced ALI in rats, we measured serum ferritin and HO-1 concentrations before and after hemorrhage. Severe hemorrhages significantly increased the number of leukocytes in bronchoalveolar lavage (BAL) fluid and lung tissue myeloperoxidase activity. Both serum ferritin and HO-1 levels increased following hemorrhage, but ferritin levels were elevated earlier than HO-1. In BAL cell immunohistochemical studies, ferritin and HO-1 expressions increased after hemorrhage and localized in the cytoplasm of leukocytes. These findings suggest that inflammatory leukocytes in BAL fluid can secrete ferritin and HO-1, and serum ferritin levels might be more valid factor in predicting ARDS than HO-1 levels in hemorrhage-induced ALI.

• Journal of Life Science
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• v.27 no.1
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• pp.8-14
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• 2017

Died Gardenia jasminoides fruit is used as a dye in the food and clothes industries in Asia. The present study investigated the anti-inflammatory effects of aqueous extract of G. jasminoides fruits (GJ) in BV-2 microglial cells. GJ inhibited lipopolysaccharide-induced nitric oxide (NO) secretion, inducible nitric oxide synthase (iNOS) expression, and reactive oxygen species production, without affecting cell viability. Furthermore, GJ increased the expression of heme oxygenase-1 (HO-1) in a dose-dependent manner. Moreover, the inhibitory effect of GJ on iNOS expression was abrogated by small interfering RNA-mediated knock-down of HO-1. In addition, GJ induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. GJ-mediated expression of HO-1 was suppressed by LY294002, a phosphoinositide 3-kinase (PI-3K) inhibitor, and SB203580, a p38 kinase inhibitor, but not by the extracellular signal-regulated kinase (ERK) inhibitor PD98059 or c-Jun N-terminal kinase (JNK) inhibitor SP600125. GJ also enhanced the phosphorylation of Akt and p38. These results suggest that GJ suppresses the production of NO, a pro-inflammatory mediator, by inducing HO-1 expression via PI-3K/Akt/p38 signaling. These findings illustrate a novel molecular mechanism by which extract from G. jasminoides fruits inhibits neuroinflammation.

• Journal of Life Science
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• v.25 no.9
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• pp.976-983
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• 2015

Achyranthoside C dimethyl ester (ACDE) is an oleanolic acid glycoside from Achyranthes japonica which has been used in traditional medicine for the treatment of edema and arthritis. In this study, we investigated the anti-inflammatory effects of ACDE in RAW264.7 macrophages. ACDE significantly induced heme oxygenase-1 (HO-1) gene expression in RAW264.7 cells, while ACDE improved LPS-induced toxicity of cells. And ACDE induced nuclear translocation of nuclear factor E2-related factor 2 (Nrf2), a transcription factor that regulates HO-1 expression. Further study demonstrated that ACDE-induced expression of HO-1 was inhibited by inhibitors of phosphatidylinositol 3-kinase (PI-3K) (LY294002), c-Jun kinase (JNK) (SP600125), extracellular signal regulated kinase (ERK) (PD98059) and p38 kinase (SB203580). Moreover, ACDE phosphorylated Akt, JNK, ERK, and p38 MAPK. In addition, ACDE inhibited LPS-induced NO secretion as well as inducible NO synthase (iNOS) expression in a dose-dependent manner. The inhibitory effects of ACDE on iNOS expression were abrogated by small interfering RNA (siRNA)-mediated knock-down of HO-1. Therefore, these results suggest that ACDE suppresses the production of pro-inflammatory mediator such as NO by inducing HO-1 expression via PI-3K/Akt/MAPK-Nrf2 signaling pathway. These findings could help us to understand the active principle included in the roots of A. japonica and the molecular mechanisms underlying anti-inflammatory action of ACDE.

• Journal of Life Science
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• v.23 no.1
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• pp.44-54
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• 2013

To determine the potential function of Rhus javanica in Korean medicine, it was fermented with each strain of Lactobacillus spp. Each strain of Lactobacillus spp. was inoculated in lactobacilli MRS broth, and 5 mg/ml of methanol extract of Rhus javanica was added. In mouse hippocampal HT22 cells, ethyl acetate extract of R. javanica fermented with L. brevis KCTC 3498 induced heme oxygenase-1 expression and showed a significant cytoprotective effect on glutamate-induced oxidative damage. The cytoprotective effect was related to the transcription of the nuclear factor E2-related factor2 (Nrf2), which is responsible for the induction of heme oxygenase-1 within the nucleus. The antimicrobial, antioxidant, and heme oxygenase-1 expression activities of fermented R. javanica were measured after extraction with ethyl acetate. R. javanica fermented with L. plantarum subsp. plantarum KCTC 3108, L. fermentum KCTC 3112, and L. brevis KCTC 3498 had higher antioxidant activity than nonfermented R. javanica. The fermented R. javanica with L. plantarum subsp. plantarum KCTC 3108, L. casei KCTC 3109 after ethyl acetate extraction showed antibacterial activity against Bacillus subtilis PCI 219, Escherichia coli KCTC 1682, Shigella flexneri KCTC 2517, Vibrio parahaemolyticus KCTC 7471, and Pseudomonas aeruginosa KCTC 2004. An ethyl acetate extract of the fermented R. javanica with Lactobacillus brevis KCTC 3498 exhibited stronger antibacterial activity than a nonfermented one against strains of B. subtilis PCI 219, E. coli KCTC 1682, S. flexneri KCTC 2517, and V. parahaemolyticus KCTC 7471.

• Journal of Life Science
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• v.18 no.11
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• pp.1485-1492
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• 2008

Prostaglandin $A_2$ ($PGA_2$), one of cyclopentenone PGs, induced both apoptosis and heme oxygenase (HO)-1 expression in U2OS cells. $PGA_2$-induced apoptosis was not perturbed by either over-expression or knock-down of HO-1, whereas $H_2O_2$-induced cell death was inversely modulated by the expression level of HO-1. In addition, N-acetyl-L-cysteine (NAC), a thiol antioxidant, blocked both apoptosis and HO-1 expression induced by $PGA_2$. But, non-thiol antioxidants like butylated hydorxyanisole (BHA) and ascorbic acid did not block either apoptosis or HO-1-induction. Taken together, these results suggest that $PGA_2$ induces both apoptosis and HO-1 expression, which are critically related to the thiol- reactivity of $PGA_2$, but not oxidative stress, and HO-1 expression may be independent or functionally located downstream of apoptosis by $PGA_2$ without contribution to apoptosis progression.

• Journal of Nutrition and Health
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• v.55 no.3
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• pp.348-358
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• 2022

Purpose: Hyperglycemia accelerates the formation of advanced glycation end products (AGEs), a group of compounds formed via non-enzymatic glycation/glycoxidation. Type 2 diabetes mellitus (T2DM) is related to oxidative stress, resulting in some overgeneration of AGEs. The accumulation of AGEs in T2DM patients leads to increased inflammation, DNA damage, tissue damage, progression of diabetic microvascular disease, and nephropathy. Heme oxygenase-1 (HO-1) is an intracellular enzyme that catalyzes the oxidation of heme. Expression of HO-1 in the endothelium and in muscle monocytes/macrophages was upregulated upon exposure to reactive oxygen species or oxidized low-density lipoprotein. Cells activated by oxidative stress are reported to release HO-1 in the serum. In the current study, we discuss the oxidative status according to the level of AGEs and the association of HO-1 with AGEs or urinary DNA damage marker in type 2 diabetic Korean patients. Methods: This study enrolled 36 diabetic patients. Subjects were classified into two groups by serum AGEs level (Low AGEs group: < 0.85 ng/mL serum AGEs; High AGEs group: ≥ 0.85 ng/mL serum AGEs). Body composition was measured using bioelectrical impedance analysis. Blood and urinary parameters were measured using commercial kits. Results: No significant differences were observed in the general characteristics and body composition between the two groups. Serum HO-1 concentration was significantly higher in the High AGEs group than in the Low AGEs group. After adjustment of age and gender, a correlation was performed to assess the association between serum HO-1 and serum AGEs or urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG). Our results indicate that serum HO-1 is positively correlated with serum AGEs and urinary 8-OHdG. Conclusion: Taken together, our results indicate that in diabetes patients, a high level of HO-1 is associated with a high concentration of AGEs and 8-OHdG, probably reflecting a protective response against oxidative stress.

• Proceedings of the PSK Conference
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• 2005.11a
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• pp.135-135
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• 2005

• Proceedings of the PSK Conference
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• 2005.11a
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• pp.136-136
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• 2005

• Proceedings of the PSK Conference
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• 2005.11a
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• pp.137-137
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• 2005

• Tuberculosis and Respiratory Diseases
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• v.60 no.3
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• pp.304-313
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• 2006

Background : Heme oxygenase-1 (HO-1) is an inducible enzyme that catalyzes the oxidative degradation of heme to form biliverdin, carbon monoxide (CO), and free iron. The current evidence has indicated a critical role of HO-1 in cytoprotection and also in other, more diverse biological functions. It is known that the high expression of HO-1 occurs in various tumors, and that HO-1 has an important role in rapid tumor growth because of its antioxidative and antiapoptotic effects. Therefore, the role of HO-1 was analyzed in human lung cancer cell lines, and especially in the A549 cell line. Material and Methods : Human lung cancer cell lines, i.e., A549, NCI-H23, NCI-H157 and NCI-H460, were used for this study. The expression of HO-1 in the untreated state was defined by Western blotting. ZnPP, which is the specific HO inhibitor we used, and the viability of cells were tested for by conducting MTT assaysy. The HO enzymatic activity, as determined via the bilirubin level, was also indirectly measured. Moreover, the generation of intracellular hydrogen peroxide (H2O2) was monitored fluorimetrically with using a scopoletin-horse radish peroxidase (HRP) assay and 2',7'-dichlorofluorescein diacetate (DCFH-DA). We have also transfected small HO-1 interfering RNA (siRNA) into A549 cells, and the apoptotic effects were evaluated by flow cytometric analysis and Western blotting. Results : The A549 cells had a greater expression of HO-1 than the other cell lines, whereas ZnPP significantly decreased the viability of the A549 cells more than the viability of the other lung cancer cells in a dose-dependant fashion. Consistent with the viability, the HO enzymatic activity also was decreased. Moreover, intracellular H2O2 generation via ZnPP was induced in a dose-dependent manner. Apoptotic events were, then induced in the HO-1 siRNA transfected A549 cells. Conclusion : HO-1 provides new important insights into the possible molecular mechanism of the antitumor therapy in lung cancer.