http://chineseinput.net/에서 pinyin(병음)방식으로 중국어를 변환할 수 있습니다.
변환된 중국어를 복사하여 사용하시면 됩니다.
- 中文 을 입력하시려면 zhongwen을 입력하시고 space를누르시면됩니다.
- 北京 을 입력하시려면 beijing을 입력하시고 space를 누르시면 됩니다.
RISS 인기검색어
- 검색키워드
- 저자 : ( Timothy R Billiar ) (검색결과 6 건)
- 무료
- 기관 내 무료
- 유료
-
Dong Hee Kim,Timothy R. Billiar 대한외과학회 2011 Annals of Surgical Treatment and Research(ASRT) Vol.80 No.3
Purpose: Transient hypoxia is an initial event that accentuates ischemia/reperfusion (I/R) injury in the liver. Hepatic ischemia/reperfusion (I/R) injury is largely related to innate immunity via Toll-like receptor 4 (TLR4) signaling. However, the mechanism by which hypoxia could lead to activate TLR4 signaling remains unclear. Therefore, the aim of this experimental study investigates how TLR4 signalling is activated by hypoxia. Methods: Hepatocytes were isolated from male wild-type (C57BL/6) mice (8∼12 weeks old) by an in situ collagenase (Type Ⅳ, Sigma-Aldrich) perfusion technique. In this study, using primary mouse hepatocytes in culture to 1% oxygen, detection of TLR4 translocation to the lipid rafts on the cell membrane by immunofluorescence staining and immunoblotting was saught. Results: Hypoxia caused TLR4/MD2 and β2-Integrin (CD11b/CD18) translocation to lipid rafts associated with CD14 in hepatocytes. The cholesterol sequestering agent, Nystatin and Filipin prevented hypoxia-induced TLR4/MD2 translocation to lipid rafts. Consistent with a role for oxidative stress in this effect, in vitro H2O2 treatment of hepatocytes similarly caused TLR4/MD2 translocation to lipid rafts. In addition, translocation of hypoxia-induced TLR4 complex was inhibited by N-acetylcysteine (NAC) demonstrating that the activation of TLR4 signaling is dependent on ROS. Further, the cholesterol sequestering agent, nystatin, prevented hypoxia-induced high mobility group box 1 (HMGB1) release in hepatocytes. Conclusion: These results suggest that ROS dependent TLR4 signaling is achieved following receptor translocation to the lipid raft in hepatocytes. We hypothesized that this mechanism is required for the release of HMGB1, an early mediator of injury and inflammation in hepatic I/R injury.
-
장광,이선진,정일영,Timothy R. Billiar,정헌택,한정아,권영근,하권수,김영명 생화학분자생물학회 2004 Experimental and molecular medicine Vol.36 No.4
The expression of inducible nitric oxide synthase (iNOS) is a critical factor in both normal physiological functions and the pathogenesis of disease. This study was undertaken to determine the m olecular m echanism by which nitric oxide (NO) exerts negative feedback regulation on iNOS gene expression. Isolated rat hepatocytes stimulated with cytokines exhibited a marked increase in NO production as well as iNOS mRNA and protein levels, which were significantly reduced by pretreatment of the NO donors S-nitroso-N-acetyl-D,L-penicillamine (SNAP) and V-PYRRO/NO. This effect of SNAP was inhibited when NO was scavenged using red blood cells. Pretreatment with oxidized SNAP, 8-Br-cGMP, NO2 -, or NO3 - did not suppress the cytokine-induced NO production. Moreover, LPS/ IFN- γ -stimulated RAW264.7 cells, which produce endogenous NO, expressed lower levels of iNOS, IL-1β, IL-6 and TNF-α mRNAs, without changes in their mRNA half-lives, than those in the presence of the iNOS inhibitor NG-monomethyl- L-arginine. The iNOS gene transcription rate exhibited an 18-fold increase after cytokine stimulation, which was significantly inhibited by SNAP pretreatment. SNAP also blocked cytokineinduced increase in NF-κB activation, iNOS promoter activity, nuclear translocation of cytosolic NF-κB p65 subunit, and IκBα degradation, which correlated with its inhibitory effect on phosphorylation and ubiquitination of IκB. These data indicate that NO down-regulates iNOS gene expression and NO production by inhibiting the post-translational processes of IκBα thereby preventing NF-κB activation. These results identify a novel negative feedback mechanism whereby NO down-regulates iNOS gene expression.
-
Nitric Oxide as a Bioregulator of Apoptosis
Chung, Hun-Taeg,Pae, Hyun-Ock,Choi, Byung-Min,Billiar, Timothy R.,Kim, Young-Myeong 원광대학교 생명공학연구소 2001 생명공학연구소보 Vol.8 No.1
Nitric oxide (NO), synthesized from L-arginine by NO synthases, is a small, diffusible, highly reactive molecule with dichotomous regulatory roles under physiological and pathological conditions. NO can promote apoptosis (proapoptosis) in some cells, whereas it inhibits apoptosis (antiapoptosis) in other cells. This complexity is a consequence of the rate of NO production and the interaction with biological molecules such as iron, thiols, proteins, and reactive oxygen species. Long-lasting production of NO acts as a pro-apoptotic modulator by activating caspase family proteases through the release of mitochondrial cytochrome c into the cytosol, upregulation of p53 expression, activation of JNK/SAPK, and altering the expression of apoptosis-associated proteins including Bcl-2 family proteins. However, low or physiological concentrations of NO prevent cells from apoptosis induced by trophic factor withdrawal, Fas, TNFα, and lipoplysaccharide. The anti-apoptotic mechanism can be understood via expression of protective genes such as heat shock proteins. Bcl-2 as well as direct inhibition of the apoptotic caspase family proteases by S-mitrosylation of the cysteine thiol. Our current understanding of the mechanisms by which NO exerts both pro- and anti-apoptotic actions is discreased in this review article.
-
Differential regulation by fucoidan of IFN‐γ‐induced NO production in glial cells and macrophages
Do, Hang,Kang, Nam‐,Sung,Pyo, Suhkneung,Billiar, Timothy R.,Sohn, Eun‐,Hwa Wiley Subscription Services, Inc., A Wiley Company 2010 Journal of cellular biochemistry Vol.111 No.5
<P><B>Abstract</B></P><P>Fucoidan has shown numerous biological actions; however, the molecular bases of these actions have being issued. We examined the effect of fucoidan on NO production induced by IFN‐γ and the molecular mechanisms underlying these effects in two types of cells including glia (C6, BV‐2) and macrophages (RAW264.7, peritoneal primary cells). Fucoidan affected IFN‐γ‐induced NO and/or iNOS expression both in macrophages and glial cells but in a contrast way. Our data showed that in C6 glioma cells both JAK/STAT and p38 signaling positively regulated IFN‐γ‐induced iNOS, which were inhibited by fucoidan. In contrast, in RAW264.7 cells JAK/STAT is a positive regulator whereas p38 is a negative regulator of NO/iNOS production. In RAW264.7 cells, fucoidan enhanced p38 activation and induced TNF‐α production. We also confirmed the dual regulation of p38 in BV‐2 microglia and primary peritoneal macrophages. From these results, we suggest that fucoidan affects not only IFN‐γ‐induced NO/iNOS production differently in brain and peritoneal macrophages due to the different roles of p38 but the effects on TNF‐α production in the two cell types. These novel observations including selective and cell‐type specific effects of fucoidan on IFN‐γ‐mediated signaling and iNOS expression raise the possibility that it alters the sensitivity of cells to the p38 activation. J. Cell. Biochem. 111: 1337–1345, 2010. © 2010 Wiley‐Liss, Inc.</P>
-
-
연관 검색어 추천
이 검색어로 많이 본 자료
활용도 높은 자료
