RISS 검색 - 국내학술지논문

무료
기관 내 무료
유료

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

1
Therapeutic effect of ent-kaur-16-en-19-oic acid on neutrophilic lung inflammation and sepsis is mediated by Nrf2

Kim, K.H.,Sadikot, R.T.,Joo, M. Academic Press 2016 Biochemical and biophysical research communication Vol.474 No.3
- 원문보기
Kaurenoic acid (ent-kaur-16-en-19-oic acid: KA) is a key constituent found in the roots of Aralia continentalis Kitagawa (Araliaceae), a remedy to treat patients with inflammatory diseases in traditional Asian medicine. Since KA activates Nrf2, a key anti-inflammatory factor, at the cellular level, we explored a possible therapeutic usage of KA against neutrophilic inflammatory lung disease such as acute lung injury (ALI). Intraperitoneal (i.p.) injection of lipopolysaccharide (LPS) to C57BL/6 mice induced lung inflammation as in ALI. 2 h after i.p. LPS, intratracheal (i.t.) delivery of KA (0.3, 3, or 30 μg/kg body weight) improved lung structure and significantly suppressed neutrophil infiltrations to mouse lungs, with concomitant reduction of myeloperoxidase activity and of the expression of pro-inflammatory cytokine genes. While activating Nrf2 and expressing Nrf2-dependent genes in mouse lungs, KA did not significantly suppress neutrophil lung inflammation in Nrf2 KO mice. In a mouse model of sepsis, a major cause of ALI, single i.t. KA (3 μg/kg) 2 h after the onset of sepsis significantly decreased the mortality of mice. Together, these results suggest that KA has a therapeutic potential against inflammatory lung disease, the effect of which is associated with Nrf2 activation.
2
Suppressed ubiquitination of Nrf2 by p47phox contributes to Nrf2 activation

Ha Kim, Kyun,Sadikot, Ruxana T.,Yeon Lee, Ji,Jeong, Han-Sol,Oh, Yu-Kyoung,Blackwell, Timothy S.,Joo, Myungsoo Elsevier 2017 FREE RADICAL BIOLOGY AND MEDICINE Vol.113 No.-
- 원문보기
Abstract Although critical in phagocytosis in innate immunity, reactive oxygen species (ROS) collaterally inflict damage to host phagocytes because they indiscriminate targets. Since Nrf2 increases the expression of anti-oxidant enzymes that nullifies ROS, ROS activating Nrf2 is a critical negative regulatory step for countering the deleterious effects of ROS. Here, we postulate whether, along with ROS activating Nrf2, NADPH oxidase components also participate in direct activation of Nrf2, contributing to protection from ROS. Our results show that the p47phox of the NADPH oxidase, but not p65phox or p40phox, physically binds to Nrf2, activating the Nrf2 function. p47phox binding to Nrf2/Keap1 complex suppresses the ubiquitination of Nrf2, while p47phox becomes ubiquitinated by Keap1. p47phox increases the nuclear translocation of Nrf2 and the expression of Nrf2-dependent genes, whereas genetic ablation of p47phox decreases the expression of those genes. In a lipopolysaccharide-induced acute lung inflammation mouse model, selective expression of p47phox in mouse lungs induces the expression of Nrf2-dependent genes and is sufficient to suppress neutrophilic lung inflammation. Therefore, our findings suggest that p47phox is a novel regulator of Nrf2 function. Highlights <UL> <LI> p47phox of NADPH oxidase binds to Nrf2, without disrupting Nrf2/Keap1 complex. </LI> <LI> p47phox binding to Nrf2 results in the ubiquitination of p47phox by Keap1. </LI> <LI> p47phox suppresses the ubiquitination of Nrf2. </LI> <LI> p47phox induces the expression of Nrf2-dependent genes in cells and mouse lungs. </LI> <LI> p47phox suppresses inflammation in a LPS-induced lung inflammation mouse model. </LI> </UL> Graphical abstract [DISPLAY OMISSION]
3
Protective Effect of the Fruit Hull of Gleditsia sinensis on LPS-Induced Acute Lung Injury Is Associated with Nrf2 Activation

Choi, Jun-Young,Kwun, Min Jung,Kim, Kyun Ha,Lyu, Ji Hyo,Han, Chang Woo,Jeong, Han-Sol,Ha, Ki-Tae,Jung, Hee-Jae,Lee, Beom-Joon,Sadikot, Ruxana T.,Christman, John W.,Jung, Sung-Ki,Joo, Myungsoo Hindawi Publishing Corporation 2012 Evidence-based Complementary and Alternative Medic Vol.2012 No.-
- 원문보기
The fruit hull of Gleditsia sinensis (FGS) has been prescribed as a traditional eastern Asian medicinal remedy for the treatment of various respiratory diseases, but the efficacy and underlying mechanisms remain poorly characterized. Here, we explored a potential usage of FGS for the treatment of acute lung injury (ALI), a highly fatal inflammatory lung disease that urgently needs effective therapeutics, and investigated a mechanism for the anti-inflammatory activity of FGS. Pretreatment of C57BL/6 mice with FGS significantly attenuated LPS-induced neutrophilic lung inflammation compared to sham-treated, inflamed mice. Reporter assays, semiquantitative RT-PCR, and Western blot analyses show that while not affecting NF-κB, FGS activated Nrf2 and expressed Nrf2-regulated genes including GCLC, NQO-1, and HO-1 in RAW 264.7 cells. Furthermore, pretreatment of mice with FGS enhanced the expression of GCLC and HO-1 but suppressed that of proinflammatory cytokines in including TNF-α and IL-1β in the inflamed lungs. These results suggest that FGS effectively suppresses neutrophilic lung inflammation, which can be associated with, at least in part, FGS-activating anti-inflammatory factor Nrf2. Our results suggest that FGS can be developed as a therapeutic option for the treatment of ALI.

내보내기
내책장담기
한글로보기

정확도순

내림차순

내림차순

10개씩 출력

맨처음 페이지로 1 맨끝 페이지로

상세검색

RISS 보유자료

상세검색

해외전자자료

연관 검색어 추천