Heme oxygenase-1 induced by desoxo-narchinol-A attenuated the severity of acute pancreatitis via blockade of neutrophil infiltration

Bae, Gi-Sang,Kim, Dong-Goo,Jo, Il-Joo,Choi, Sun-Bok,Kim, Myoung-Jin,Shin, Joon Yeon,Kim, Dong-Uk,Song, Ho-Joon,Joo, Myungsoo,Park, Sung-Joo ELSEVIER 2019 INTERNATIONAL IMMUNOPHARMACOLOGY Vol.69 No.-

<P><B>Abstract</B></P> <P>Heme oxygenase-1 (HO-1) has an anti-inflammatory action in acute pancreatitis (AP). However, its mechanism of action and natural compounds/drugs to induce HO-1 in pancreas are not well understood. In this study, we investigated the regulatory mechanisms of HO-1 during AP using desoxo-narchinol-A (DN), the natural compound inducing HO-1 in the pancreas. Female C57/BL6 Mice were intraperitoneally injected with supramaximal concentrations of cerulein (50 μg/kg) hourly for 6 h to induce AP. DMSO or DN was administered intraperitoneally, then mice were sacrificed 6 h after the final cerulein injection. Administration of DN increased pancreatic HO-1 expression through activation of activating protein-1, mediated by mitogen-activated protein kinases. Furthermore, DN treatment reduced the pancreatic weight-to-body weight ratio as well as production of digestive enzymes and pro-inflammatory cytokines. Inhibition of HO-1 by tin protoporphyrin IX abolished the protective effects of DN on pancreatic damage. Additionally, DN treatment inhibited neutrophil infiltration into the pancreas via regulation of chemokine (C-X-C motif) ligand 2 (CXCL2) by HO-1. Our results suggest that DN is an effective inducer of HO-1 in the pancreas, and that HO-1 regulates neutrophil infiltration in AP via CXCL2 inhibition.</P> <P><B>Highlights</B></P> <P> <UL> <LI> Desoxo-narchinol-A (DN) is a natural compound of HO-1 inducer in pancreas. </LI> <LI> Mechanism of DN-induced HO-1 is mediated by MAPK/Activator Protein-1/HO-1 signaling. </LI> <LI> DN-induced HO-1 blocks neutrophil infiltration into pancreas via inhibition of CXCL2. </LI> <LI> DN inhibits cerulein-induced acute pancreatitis (AP) and AP-associated lung injury. </LI> </UL> </P> <P><B>Graphical abstract</B></P> <P>[DISPLAY OMISSION]</P>

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Shin, Tae-Kyeong,Kang, Mi-Sun,Lee, Ho-Youn,Seo, Moo-Sang,Kim, Si-Geun,Kim, Chi-Dae,Lee, Won-Suk The Korean Society of Pharmacology 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1 ${\alpha}$ (HIF-1 ${\alpha}$) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1 ${\alpha}$ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Fatigue Crack Growth Behavior in Ultrafine Grained Low Carbon Steel

Ho,Kyung Kim,Myung-Il Choi,Chin-Sung Chung Dong-Hyuk Shin 대한기계학회 2002 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.16 No.10

Ultrafine grained (UFG) low carbon (0.15 wt.% C) steel produced by equal channel angular pressing (ECAP) was tested for investigating the effect of load ratio on the fatigue crack growth rate. Fatigue crack growth resistance and threshold of UFG steel were lower than that of as-received coarse grained steel. It was attributed to the less tortuous crack path. The UFG steel exhibited slightly higher crack growth rates and a lower △K_th with an increase of R ratio. The R ratio effect on crack growth rates and △K_th was basically indistinguishable at lower load ratio (R>0.3), compared to other alloys, which indicates that contribution of the crack closure vanishes. The crack growth rate curve for UFG steel exhibited a longer linear extension to the lower growth rate regime than that for the coarse grained as-received steel.<br/>

권역단위 농촌지역개발사업의 주민역량 측정을 위한 설문도구개발

리신호 ( Shin Ho Rhee ),민흥기 ( Heung Gi Min ),윤성수 ( Sung Soo Yoon ),정남수 ( Nam Su Jung ),장우석 ( Woo Seok Chang ) 한국농촌계획학회 2014 농촌계획 Vol.20 No.4

The purpose of this study was to develop survey tools for diagnosis of capacity levels in business promotion of rural residents when performing a rural development project of a regional unit. The cases of previous studies were analyzed to select community capacity indicators related to a rural development project. Five indicators were derived : social capital, consciousness of participation, community spirit, and leadership. Based on the five indicators, measurement items of various capacities were selected and 54 survey items were selected through evaluation of experts twice. The pilot tests were conducted and targeted at Jeonnam song ho-jung village and Gyeongnam Haegeumgang village to identify derived survey items. In addition, descriptive statistic analysis and reliability analysis were conducted. As a result, survey items were corrected by reducing 10 items of the total 54 items. This results showed that using this tool could help us understand capacity levels of rural residents.

Induction of heme oxygenase-1 protects against podocyte apoptosis under diabetic conditions

Lee, Sang Choel,Han, Seung Hyeok,Li, Jin Ji,Lee, Sun Ha,Jung, Dong-Sub,Kwak, Seung-Jae,Kim, Seung Hye,Kim, Dong Ki,Yoo, Tae-Hyun,Kim, Jin Hyun,Chang, Se-Ho,Han, Dae Suk,Kang, Shin-Wook International Society of Nephrology 2009 Kidney international Vol.76 No.8

Heme oxygenase-1 (HO-1) is an anti-oxidant enzyme normally upregulated in response to oxidant injury. Here we determined the role of HO-1 in podocyte apoptosis in glomeruli of streptozotocin-treated rats and in immortalized mouse podocytes cultured in media containing normal or high glucose. HO-1 expression, its activity, the ratio of Bax/Bcl-2 protein, and active caspase-3 fragments were all significantly higher in isolated glomeruli of diabetic rats and in high glucose–treated podocytes. These increases were inhibited by zinc protoporphyrin treatment of the rats or by HO-1 siRNA treatment of the podocytes in culture. The number of apoptotic cells was also significantly increased in the glomeruli of diabetic rats and in high glucose–treated podocytes. Inhibition of HO-1 accentuated the increase in apoptotic cells both in vivo and in vitro. Our findings suggest that HO-1 expression protects against podocyte apoptosis under diabetic conditions.

Fluoxetine and Sertraline Attenuate Postischemic Brain Injury in Mice

Tae Kyeong Shin,Mi Sun Kang,Ho Youn Lee,Moo Sang Seo,Si Geun Kim,Chi Dae Kim,Won Suk Lee 대한생리학회-대한약리학회 2009 The Korean Journal of Physiology & Pharmacology Vol.13 No.3

This study aimed to investigate whether selective serotonin reuptake inhibitors (SSRIs) attenuate brain injury and facilitate recovery following photothrombotic cortical ischemia in mice. Male ICR mice were anesthetized and systemically administered Rose Bengal. Permanent focal ischemia was induced in the medial frontal and somatosensory cortices by irradiating the skull with cold light laser. The animals were treated with fluoxetine or sertraline once a day for 14 d starting 1 h after ischemic insult. Treatment with fluoxetine and sertraline significantly reduced the infarct size. The Evans blue extravasation indices of the fluoxetine- and sertraline-treated groups were significantly lower than that of the vehicle group. Treatment with fluoxetine and sertraline shifted the lower limit of the mean arterial blood pressure for cerebral blood flow autoregulation toward normal, and significantly increased the expression of heme oxygenase-1 (HO-1) and hypoxia-inducible factor-1Ձ (HIF-1Ձ) proteins in the ischemic region. These results suggest that SSRIs, such as fluoxetine and sertraline, facilitate recovery following photothrombotic cortical ischemia via enhancement of HO-1 and HIF-1Ձ proteins expression, thereby providing a benefit in therapy of cerebral ischemia.

Intracavitary Radiation Therapy for Recurrent Cystic Brain Tumors with Holmium-166-Chico : A Pilot Study

Ha, Eun Jin,Gwak, Ho-Shin,Rhee, Chang Hun,Youn, Sang Min,Choi, Chang-Woon,Cheon, Gi Jeong The Korean Neurosurgical Society 2013 Journal of Korean neurosurgical society Vol.54 No.3

Objective : Intracavitary injection of beta-emitting radiation source for control of cystic tumors has been tried with a benefit of localized internal radiation. The authors treated cystic brain tumor patients with Holmium-166-chitosan complex (Ho-166-chico), composed of a beta-emitting radionuclide Holmium-166 and biodegradable chit polymer, and evaluated the safety and effective measurement for response. Methods : Twenty-two patients with recurrent cystic brain tumor and/or located in a deep or eloquent area were enrolled in this pilot study. The cyst volume and wall thickness were determined on CT or MRI to assess radiological response. The activity of Ho-166-chico injected via Ommaya reservoir was prescribed to be 10-25 Gy to the cyst wall in a depth of 4 mm. Results : There was neither complications related to systemic absorption nor leakage of Ho-166-chico in all 22 patients. But, two cases of oculomotor paresis were observed in patients with recurrent craniopharyngioma. Radiological response was seen in 14 of 20 available follow-up images (70%). Seven patients of 'evident' radiological response experienced more than 25% decrease of both cyst volume and wall thickness. Another 7 patients with 'suggestive' response showed decrease of cyst volume without definitive change of the wall thickness or vice versa. All patients with benign tumors or low grade gliomas experienced symptomatic improvement. Conclusion : Ho-166-chico intracavitary radiation therapy for cystic tumor is a safe method of palliation without serious complications. The determination of both minimal effective dosage and time interval of repeated injection through phase 1 trial could improve the results in the future.

Curcumin protects retinal pigment epithelial cells against oxidative stress via induction of heme oxygenase-1 expression and reduction of reactive oxygen

Woo, Je Moon,Shin, Da-Yong,Lee, Sung Ju,Joe, Yeonsoo,Zheng, Min,Yim, Jin Ho,Callaway, Zak,Chung, Hun Taeg Molecular Vision 2012 Molecular vision Vol.18 No.-

<P><B>Purpose</B></P><P>To determine whether curcumin induces expression of the defensive enzyme heme oxygenase-1 (HO-1) and protects cells against oxidative stress in cultured human retinal pigment epithelial cells.</P><P><B>Methods</B></P><P>Effective concentrations and toxicities of curcumin were determined after 3 h of curcumin treatment with the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Confluent human retinal pigment epithelium cell lines (ARPE-19) were preincubated with curcumin and oxidatively challenged with H<SUB>2</SUB>O<SUB>2</SUB>. HO-1 expression was determined with western blot analysis. To confirm the protective role of HO-1 in oxidative stress, small interfering RNA (siRNA) against HO-1 or inhibitor of HO-1 was treated with curcumin in retinal pigment epithelium cells. Intracellular levels of reactive oxygen species (ROS) were measured with flow cytometry and confocal microscopy. Apoptosis was evaluated with Annexin V-fluoroscein isothiocyanate staining.</P><P><B>Results</B></P><P>Curcumin had little cytotoxicity at concentrations less than 30 μM, and HO-1 expression was the highest at the 15 μM concentration. At this concentration, curcumin also increased the cytoprotective effect against the oxidative stress of H<SUB>2</SUB>O<SUB>2</SUB> through the reduction of ROS levels in human retinal pigment epithelial cells. Curcumin’s effect on the reduction of ROS was mediated by the increase in HO-1 expression.</P><P><B>Conclusions</B></P><P>Curcumin upregulated the oxidative stress defense enzyme HO-1 and may protect human retinal pigment epithelial cells against oxidative stress by reducing ROS levels.</P>

Antioxidant activity in vitro and mucosal protective effect of Rhei Rhizoma on reflux esophagitis induced in rats

Ah Reum Lee,Yu Ock Shin,Joo Young Lee,Min Yeong Kim,Sung Ho Shin,Bu-Il Seo,Young-Bae Seo,Man Hee Rhee,TakakoYokozawa,Chan Hum Park,Seong-SooRoh 한국약용작물학회 2015 한국약용작물학술대회 발표집 Vol.2015 No.05

Purpose Rhei Rhizoma (RR) is one of the herbal medicines traditionally used to treat diverse inflammatory diseases. The present study was undertaken to elucidate the antioxidant and anti-inflammatory activities of Rhei Rhizoma on experimental reflux esophagitis (RE) in rats. Methods The antioxidant activity of RR in vitro was measured in terms of radical scavenging capacity such as DPPH and ABTS. RE was produced by ligating both the pylorus and the transitional junction between the forestomach and the corpus. Rhei Rhizoma (125 and 250 mg/kg) were administered every day for 7 days, and its effect was estimated on comparison with RE control and normal rats. Results RR scavenged DPPH and ABTS effectively and IC50ofDPPH and ABTS radical scavenging activity of RR were 4.8 μg/ml and 15.75 μg/ml. The administration of RR decreased the elevated serum ROS in RE control rats. The RE control rats exhibited the down-regulation of antioxidant-related proteins such as Nrf2 and HO-1expression levels in the esophagitis; however, the level in the RR-treated RE rats was significantly higher than that in the RE control rats. Moreover, RE control rats exhibited the up-regulation of the protein expression related to oxidative stress at the esophagitis, but RR administration significantly reduced the expression of inflammatory proteins through the MAPK-independent signaling pathways. The expression of inflammatory mediators and cytokines by NF-κB activation was modulated through blocking the degradation of IκBα. In addition, the oral administration of RR regulated the gastric mucosal damage in RE rats. Conclusion The administration of Rhei Rhizoma effectively ameliorates the inflammatory damage of esophageal mucosa through radical scavenging activity and the activation of the Nrf2/HO-1 pathway.

<i>Toxoplasma gondii</i> protects against H₂O₂‐induced apoptosis in ARPE‐19 cells through the transcriptional regulation of apoptotic elements and downregulation of the p38 MAPK pathway

Choi, Si‐,Hwan,Park, Sung Jun,Cha, Guang‐,Ho,Quan, Juan Hua,Chang, Nam‐,Sik,Ahn, Myoung‐,Hee,Shin, Dae‐,Whan,Lee, Young‐,Ha Blackwell Publishing Ltd 2011 Acta ophthalmologica Vol.89 No.4

<P><B>Abstract.</B></P><P><B>Purpose: </B> Toxoplasmosis, which is caused by the protozoan parasite <I>Toxoplasma gondii</I>, can lead to severe visual impairment. <I>T.?gondii</I> inhibits or delays programmed cell death caused by various apoptotic triggers; however, the mechanisms involved in the <I>T</I>.?<I>gondii</I>‐induced suppression of apoptosis in retinal cells have not been analysed in detail.</P><P><B>Methods: </B> We investigated the role of <I>T</I>.<I>?gondii</I> infection in H<SUB>2</SUB>O<SUB>2</SUB>‐induced apoptosis in human retinal pigment epithelial cells (ARPE‐19) by monitoring the activities of apoptosis‐regulating molecules and mitogen‐activated protein kinases (MAPKs), including p38 MAPK. We also examined the gene downstream from p38 MAPK.</P><P><B>Results: </B> <I>T.?gondii</I> infection significantly inhibited the cellular toxicity of H<SUB>2</SUB>O<SUB>2</SUB> (500 μ<SMALL>m</SMALL>) and increased cell viability in a multiplicity of infection (MOI)‐dependent manner by reducing DNA fragmentation and reactive oxygen species (ROS) generation in ARPE‐19 cells. Western blot analysis also showed that <I>T</I>.?<I>gondii</I> infection prevented the host cell expression of pro‐apoptotic factors, such as Bad and Bax, and the activation of caspase‐3. Infection with <I>T</I>.?<I>gondii</I> increased the expression of the anti‐apoptotic factor Bcl‐2 in ARPE‐19 cells under oxidative stress. In accordance with these findings, <I>Toxoplasma</I> infection was protective enough to suppress the phosphorylation of p38 MAPK following H<SUB>2</SUB>O<SUB>2</SUB> treatment. Exposure to H<SUB>2</SUB>O<SUB>2</SUB> increased the expression of heme oxygenase‐1 (HO‐1) in ARPE‐19 cells, and its expression was significantly inhibited in H<SUB>2</SUB>O<SUB>2</SUB>‐treated infected cells.</P><P><B>Conclusion: </B> The protective function of <I>T</I>.?<I>gondii</I> infection against ROS‐induced apoptosis results from changes in the expression of apoptotic molecules and the downregulation of stress‐induced intracellular signalling.</P>