Active Transport, Cell Nucleus

Publication Title: 
Molecular Cell

Forkhead box O (FOXO; DAF-16 in worms) transcription factors, which are of vital importance in cell-cycle control, stress resistance, tumor suppression, and organismal lifespan, are largely regulated through nucleo-cytoplasmic shuttling. Insulin signaling keeps FOXO/DAF-16 cytoplasmic, and hence transcriptionally inactive. Conversely, as in loss of insulin signaling, reactive oxygen species (ROS) can activate FOXO/DAF-16 through nuclear accumulation. How ROS regulate the nuclear translocation of FOXO/DAF-16 is largely unknown.

Putker, Marrit
Madl, Tobias
Vos, Harmjan R.
de Ruiter, Hesther
Visscher, Marieke
van den Berg, Maaike C. W.
Kaplan, Mohammed
Korswagen, Hendrik C.
Boelens, Rolf
Vermeulen, Michiel
Burgering, Boudewijn M. T.
Dansen, Tobias B.
Publication Title: 
Infection and Immunity

Sequestration of Plasmodium falciparum-infected erythrocytes (Pf-IRBC) in postcapillary brain endothelium is a hallmark of cerebral malaria (CM) pathogenesis. There is a correlation between adherent Pf-IRBC and increased expression of intercellular cell adhesion molecule 1 (ICAM-1), which is also a receptor for Pf-IRBC on human brain microvascular endothelial cells (HBMEC). The underlying mechanism for the increased ICAM-1 expression has not been clearly defined. Therefore, we investigated the mechanisms of ICAM-1 expression on isolated HBMEC after exposure to Pf-IRBC.

Tripathi, Abhai K.
Sullivan, David J.
Stins, Monique F.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Glucosamine represents one of the most commonly used drugs to treat osteoarthritis. However, mechanisms of its antiarthritic activities are still poorly understood. The present study identifies a novel mechanism of glucosamine-mediated anti-inflammatory activity. It is shown that both glucosamine and N-acetylglucosamine inhibit IL-1beta- and TNF-alpha-induced NO production in normal human articular chondrocytes.

Shikhman, A. R.
Kuhn, K.
Alaaeddine, N.
Lotz, M.
Publication Title: 
Arthritis and Rheumatism

OBJECTIVE: The mechanisms by which chondrocytes convert biomechanical signals into intracellular biochemical events are not well understood. In this study, we sought to determine the intracellular mechanisms of the magnitude-dependent actions of mechanical signals. METHODS: Chondrocytes isolated from rabbit articular cartilage were grown on flexible membranes. Cells were subjected to cyclic tensile strain (CTS) of various magnitudes in the presence or absence of interleukin-1beta (IL-1beta), which was used as a proinflammatory signal for designated time intervals.

Agarwal, Sudha
Deschner, James
Long, Ping
Verma, Anupam
Hofman, Cynthia
Evans, Christopher H.
Piesco, Nicholas
Publication Title: 
American Journal of Respiratory Cell and Molecular Biology

Cystic fibrosis (CF) is characterized by prolonged and excessive inflammatory responses in the lung and increased activation of NF-kappaB. Parthenolide is a sesquiterpene lactone derived from the plant feverfew, which has been used in folk medicine for anti-inflammatory activity. Several studies suggest that this compound inhibits the NF-kappaB pathway, but the exact site is controversial. We hypothesized that parthenolide might ameliorate the excessive inflammatory response in CF models by inhibiting activation of NF-kappaB.

Saadane, Aicha
Masters, Sophia
DiDonato, Joseph
Li, Jingfeng
Berger, Melvin
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

In response to inflammatory stimuli (e.g., endotoxin, proinflammatory cytokines) or oxidative stress, macrophages actively release a ubiquitous nuclear protein, high-mobility group box 1 (HMGB1), to sustain an inflammatory response to infection or injury. In this study, we demonstrated mild heat shock (e.g., 42.5 degrees C, 1 h), or enhanced expression of heat shock protein (Hsp) 72 (by gene transfection) similarly rendered macrophages resistant to oxidative stress-induced HMGB1 cytoplasmic translocation and release.

Tang, Daolin
Kang, Rui
Xiao, Weimin
Jiang, Lei
Liu, Meidong
Shi, Yongzhong
Wang, Kangkai
Wang, Haichao
Xiao, Xianzhong
Publication Title: 

Soy phytoestrogens have been proposed as an alternative to estrogen replacement therapy and have demonstrated potential neuroprotective effects in the brain. We have shown that a high soy diet significantly reduces infarct size following permanent middle cerebral artery occlusion (MCAO). Here, we tested the hypothesis that a high soy diet would attenuate programmed cell death after stroke.

Lovekamp-Swan, T.
Glendenning, M.
Schreihofer, D. A.
Publication Title: 
Journal of Immunology (Baltimore, Md.: 1950)

Exercise/joint mobilization is therapeutic for inflammatory joint diseases like rheumatoid and osteoarthritis, but the mechanisms underlying its actions remain poorly understood. We report that biomechanical signals at low/physiological magnitudes are potent inhibitors of inflammation induced by diverse proinflammatory activators like IL-1beta, TNF-alpha, and lipopolysaccharides, in fibrochondrocytes.

Madhavan, Shashi
Anghelina, Mirela
Sjostrom, Danen
Dossumbekova, Anar
Guttridge, Denis C.
Agarwal, Sudha
Publication Title: 
Thrombosis and Haemostasis

High-mobility group box 1 protein (HMGB1), an abundant nuclear protein, was recently established as a proinflammatory mediator of experimental sepsis. Although extracellular HMGB1 has been found in atherosclerotic plaques, its potential role in the pathogenesis of atherothrombosis remains elusive. In the present study, we determined whether HMGB1 induces tissue factor (TF) expression in vascular endothelial cells (ECs) and macrophages. Our data showed that HMGB1 stimulated ECs to express TF (but not TF pathway inhibitor) mRNA and protein in a concentration- and time-dependent manner.

Lv, Ben
Wang, Haichao
Tang, Yiting
Fan, Zhang
Xiao, Xianzhong
Chen, Fangping
Publication Title: 
Stroke; a Journal of Cerebral Circulation

BACKGROUND AND PURPOSE: Carbon monoxide (CO) is a gaseous second messenger produced when heme oxygenase enzymes catabolize heme. We have demonstrated that CO can be therapeutic in ischemia-reperfusion brain injury; however, it is unclear whether CO can also offer protection in permanent ischemic stroke or what mechanism(s) underlies the effect. Heme oxygenase-1 neuroprotection was shown to be regulated by Nrf2; therefore, we investigated whether CO might partially exert neuroprotection by modulating the Nrf2 pathway.

Wang, Bing
Cao, Wangsen
Biswal, Shyam
Doré, Sylvain


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