Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells

Chin-Ok Yi,Byeong Tak Jeon,Hyun Joo Shin,Eun Ae Jeong,Ki Churl Chang,Jung Eun Lee,Dong Hoon Lee,Hyun Joon Kim,Sang Soo Kang,Gyeong Jae Cho,Wan Sung Choi,Gu Seob Roh 대한해부학회 2011 Anatomy & Cell Biology Vol.44 No.3

AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E2 production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.

Resveratrol activates AMPK and suppresses LPS-induced NF-κB-dependent COX-2 activation in RAW 264.7 macrophage cells

Yi, Chin-Ok,Jeon, Byeong Tak,Shin, Hyun Joo,Jeong, Eun Ae,Chang, Ki Churl,Lee, Jung Eun,Lee, Dong Hoon,Kim, Hyun Joon,Kang, Sang Soo,Cho, Gyeong Jae,Choi, Wan Sung,Roh, Gu Seob Korean Association of Anatomists 2011 Anatomy & Cell Biology Vol.44 No.3

<P>AMP-activated protein kinase (AMPK), an enzyme involved in energy homeostasis, regulates inflammatory responses, but its precise mechanisms are not fully understood. Recent evidence has shown that resveratrol (RES), an AMPK activator, reduces prostaglandin E<SUB>2</SUB> production in lipopolysaccharide (LPS)-treated microglia. Here, we examined the effect of RES on nuclear factor kappa B (NF-κB) dependent cyclooxygenase (COX)-2 activation in LPS-treated RWA 264.7 macrophages. We found that treatment with RES increased AMPK activation. AMPK and acetyl CoA carboxylase phosphorylation were attenuated in cells treated with LPS+RES, compared to cells treated with LPS alone. RES inhibited tumor necrosis factor (TNF)-α and TNF receptor 1 in LPS-treated cells. Finally, RES inhibited LPS-induced NF-κB translocation into the nucleus and COX-2 expression. Moreover, the effects of 5-aminoimidazole-4-carboxamide ribose and compound C were consistent with the effects of RES in LPS-treated cells. Taken together, these results suggest that the anti-inflammatory action of RES in RAW 264.7 macrophages is dependent on AMPK activation and is associated with inhibition of the LPS-stimulated NF-κB-dependent COX-2 signaling pathway.</P>

Triterpenes with cytotoxicity from the leaves of Vernicia fordii.

Pei, Yi-Hua,Kwon, Ok-Kyoung,Lee, Ji-Seon,Cha, Hyuk-Jin,Ahn, Kyung-Seop,Oh, Sei-Ryang,Lee, Hyeong-Kyu,Chin, Young-Won Pharmaceutical Society of Japan 2013 Chemical & pharmaceutical bulletin Vol.61 No.6

<P>Two new triterpenes, (1α,3β,8α,9β,10α,13α,14β)-9,10-dimethyl-25,26-dinorolean-5-en-1,3-diol (1) and (1α,3β,6β)-olean-12-en-1,3,6-triol (2) were isolated from the leaves of Aleurites fordii, together with five known triterpenes. The structures of isolates were established by one dimensional (1D)- and 2D-NMR spectroscopic data along with MS analysis. Of the isolated compounds, 1, 2 and 4 (daturadiol) displayed moderate cytotoxicities against two or more human cancer cell lines in HepG2 (hepatocellular carcinoma), SK-OV-3 (ovarian carcinoma), A-549 (lung carcinoma) and SNU-1 (gastric carcinoma).</P>

Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

Yu Ji Cho,Chin Ok Yi,Byeong Tak Jeon,Yi Yeong Jeong,Gi Mun Kang,Jung Eun Lee,Gu Seob Roh,Jong Deog Lee 대한생리학회-대한약리학회 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-Ղ1 (TGF-Ղ1), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-Ձ (TNF-Ձ), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-ՊB (NF-ՊB) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Curcumin Attenuates Radiation-Induced Inflammation and Fibrosis in Rat Lungs

Cho, Yu Ji,Yi, Chin Ok,Jeon, Byeong Tak,Jeong, Yi Yeong,Kang, Gi Mun,Lee, Jung Eun,Roh, Gu Seob,Lee, Jong Deog The Korean Society of Pharmacology 2013 The Korean Journal of Physiology & Pharmacology Vol.17 No.4

A beneficial radioprotective agent has been used to treat the radiation-induced lung injury. This study was performed to investigate whether curcumin, which is known to have anti-inflammatory and antioxidant properties, could ameliorate radiation-induced pulmonary inflammation and fibrosis in irradiated lungs. Rats were given daily doses of intragastric curcumin (200 mg/kg) prior to a single irradiation and for 8 weeks after radiation. Histopathologic findings demonstrated that macrophage accumulation, interstitial edema, alveolar septal thickness, perivascular fibrosis, and collapse in radiation-treated lungs were inhibited by curcumin administration. Radiation-induced transforming growth factor-${\beta}1$ (TGF-${\beta}1$), connective tissue growth factor (CTGF) expression, and collagen accumulation were also inhibited by curcumin. Moreover, western blot analysis revealed that curcumin lowered radiation-induced increases of tumor necrosis factor-${\alpha}$ (TNF-${\alpha}$), TNF receptor 1 (TNFR1), and cyclooxygenase-2 (COX-2). Curcumin also inhibited the nuclear translocation of nuclear factor-${\kappa}B$ (NF-${\kappa}B$) p65 in radiation-treated lungs. These results indicate that long-term curcumin administration may reduce lung inflammation and fibrosis caused by radiation treatment.

Atorvastatin pretreatment attenuates kainic acid-induced hippocampal neuronal death via regulation of lipocalin-2-associated neuroinflammation

Jin, Zhen,Jung, Yohan,Yi, Chin-ok,Lee, Jong Youl,Jeong, Eun Ae,Lee, Jung Eun,Park, Ki-Jong,Kwon, Oh-Young,Lim, Byeong Hoon,Choi, Nack-Cheon,Roh, Gu Seob The Korean Society of Pharmacology 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.3

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

Atorvastatin pretreatment attenuates kainic acid

Zhen Jin,Yohan Jung,Chin-ok Yi,Jong Youl Lee,Eun Ae Jeong,Jung Eun Lee,Ki-Jong Park,Oh-Young Kwon,Byeong Hoon Lim,Nack-Cheon Choi,Gu Seob Roh 대한생리학회-대한약리학회 2018 The Korean Journal of Physiology & Pharmacology Vol.22 No.3

Statins mediate vascular protection and reduce the prevalence of cardiovascular diseases. Recent work indicates that statins have anticonvulsive effects in the brain; however, little is known about the precise mechanism for its protective effect in kainic acid (KA)-induced seizures. Here, we investigated the protective effects of atorvastatin pretreatment on KA-induced neuroinflammation and hippocampal cell death. Mice were treated via intragastric administration of atorvastatin for 7 days, injected with KA, and then sacrificed after 24 h. We observed that atorvastatin pretreatment reduced KA-induced seizure activity, hippocampal cell death, and neuroinflammation. Atorvastatin pretreatment also inhibited KA-induced lipocalin-2 expression in the hippocampus and attenuated KA-induced hippocampal cyclooxygenase-2 expression and glial activation. Moreover, AKT phosphorylation in KA-treated hippocampus was inhibited by atorvastatin pretreatment. These findings suggest that atorvastatin pretreatment may protect hippocampal neurons during seizures by controlling lipocalin-2-associated neuroinflammation.

국내외 실태조사 분석을 통한 연안역 안전시설의 개선방향

배현웅(Bae, Hyun-Ung),이규세(Yi, Gyu-Sei),이진옥(Lee, Chin-Ok),임남형(Lim, Nam-Hyoung) 한국산학기술학회 2013 한국산학기술학회논문지 Vol.14 No.1

최근 해양관련 레저 활동 및 관광의 활성화로 연안역에서의 안전사고 위험은 더욱 증가하고 있다. 그러나 현재 안전사고를 방지하기 위한 안전시설의 기술적 측면이나 관리적 측면에 대한 규정이 부재하여 연안역 안전사고 대책이 안전사고의 증가속도에 적절하게 대응하지 못하고 있는 실정이다. 연안역의 지리적, 환경적 조건은 육역과 해 역의 특성이 혼재되어있으며 또한, 다양한 많은 활동(어업, 항만업, 관광, 레저)이 존재하므로 안전사고를 방지하기 위 한 안전시설을 설치하는 경우에는 육역 및 해역의 특성과 어부/항만노동자/관광객/레저활동자들의 행동특성이 적절히 고려되어야 한다. 본 논문에서는 국내 및 국외(홍콩, 마카오) 실태조사를 실시하였으며, 이로부터 국내 연안역의 안전 시설에 대한 현안 문제점을 제시하였다. 또한 안전시설에 대한 개선방향을 제안하였다. Recently, the risk of safety accidents in the coastal zone has been increased due to revitalization of marine leisure and tourism. Because of a lack of regulations about technical and maintenance aspect for safety facilities, the effective measures to prevent safety accidents in the coastal zone have not taken with increasing rate of the accidents. The nature of land/sea and behavioral characteristics of a fisherman/port laborer/tourist/people at leisure should be taken into account properly when safety facilities to prevent safety accidents in the coastal zone are installed, since the characteristics of land/sea and many activities such as fishery, harbor works, tour, leisure are mixed in the geographic and environmental condition of the coastal zone. This study analyzes the current problems on the safety facility in the domestic coastal zone through the domestic and foreign(Hongkong, Macau) field survey. Also the direction of the improvement about the safety facility are proposed.

Myeloid-specific SIRT1 Deletion Aggravates Hepatic Inflammation and Steatosis in High-fat Diet-fed Mice

Kim, Kyung Eun,Kim, Hwajin,Heo, Rok Won,Shi, Hyun Joo,Yi, Chin-ok,Lee, Dong Hoon,Kim, Hyun Joon,Kang, Sang Soo,Cho, Gyeong Jae,Choi, Wan Sung,Roh, Gu Seob The Korean Society of Pharmacology 2015 The Korean Journal of Physiology & Pharmacology Vol.19 No.5

Sirtuin 1 (SIRT1) is a mammalian $NAD^+$-dependent protein deacetylase that regulates cellular metabolism and inflammatory response. The organ-specific deletion of SIRT1 induces local inflammation and insulin resistance in dietary and genetic obesity. Macrophage-mediated inflammation contributes to insulin resistance and metabolic syndrome, however, the macrophage-specific SIRT1 function in the context of obesity is largely unknown. C57/BL6 wild type (WT) or myeloid-specific SIRT1 knockout (KO) mice were fed a high-fat diet (HFD) or normal diet (ND) for 12 weeks. Metabolic parameters and markers of hepatic steatosis and inflammation in liver were compared in WT and KO mice. SIRT1 deletion enhanced HFD-induced changes on body and liver weight gain, and increased glucose and insulin resistance. In liver, SIRT1 deletion increased the acetylation, and enhanced HFD-induced nuclear translocation of nuclear factor kappa B (NF-${\kappa}B$), hepatic inflammation and macrophage infiltration. HFD-fed KO mice showed severe hepatic steatosis by activating lipogenic pathway through sterol regulatory element-binding protein 1 (SREBP-1), and hepatic fibrogenesis, as indicated by induction of connective tissue growth factor (CTGF), alpha-smooth muscle actin (${\alpha}$-SMA), and collagen secretion. Myeloid-specific deletion of SIRT1 stimulates obesity-induced inflammation and increases the risk of hepatic fibrosis. Targeted induction of macrophage SIRT1 may be a good therapy for alleviating inflammation-associated metabolic syndrome.

Exendin-4 Improves Nonalcoholic Fatty Liver Disease by Regulating Glucose Transporter 4 Expression in ob/ob Mice

Kim, Seok,Jung, Jaehoon,Kim, Hwajin,Heo, Rok Won,Yi, Chin-Ok,Lee, Jung Eun,Jeon, Byeong Tak,Kim, Won-Ho,Hahm, Jong Ryeal,Roh, Gu Seob The Korean Society of Pharmacology 2014 The Korean Journal of Physiology & Pharmacology Vol.18 No.4

Exendin-4 (Ex-4), a glucagon-like peptide-1 receptor (GLP-1R) agonist, has been known to reverse hepatic steatosis in ob/ob mice. Although many studies have evaluated molecular targets of Ex-4, its mechanism of action on hepatic steatosis and fibrosis has not fully been determined. In the liver, glucose transporter 4 (GLUT4) is mainly expressed in hepatocytes, endothelial cells and hepatic stellate cells (HSCs). In the present study, the effects of Ex-4 on GLUT4 expression were determined in the liver of ob/ob mice. Ob/ob mice were treated with Ex-4 for 10 weeks. Serum metabolic parameters, hepatic triglyceride levels, and liver tissues were evaluated for hepatic steatosis. The weights of the whole body and liver in ob/ob mice were reduced by long-term Ex-4 treatment. Serum metabolic parameters, hepatic steatosis, and hepatic fibrosis in ob/ob mice were reduced by Ex-4. Particularly, Ex-4 improved hepatic steatosis by enhancing GLUT4 via GLP-1R activation in ob/ob mice. Ex-4 treatment also inhibited hepatic fibrosis by decreasing expression of connective tissue growth factor in HSCs of ob/ob mice. Our data suggest that GLP-1 agonists exert a protective effect on hepatic steatosis and fibrosis in obesity and type 2 diabetes.