Interdependent serotonin transporter and receptor pathways regulate S100A4/Mts1, a gene associated with pulmonary vascular disease.
AuthorsLawrie A, Spiekerkoetter E, Martinez EC, Ambartsumian N, Sheward WJ, MacLean MR, Harmar AJ, Schmidt AM, Lukanidin E, Rabinovitch M,
JournalCirc Res
PubMed ID16002749
Heightened expression of the S100 calcium-binding protein, S100A4/Mts1, is observed in pulmonary vascular disease. Loss of serotonin (5-hydroxytryptamine [5-HT]) receptors or of the serotonin transporter (SERT) attenuates pulmonary hypertension in animals, and polymorphisms causing gain of SERT function are linked to clinical pulmonary vascular disease. Because 5-HT induces release of ... More
Pairwise network mechanisms in the host signaling response to coxsackievirus B3 infection.
AuthorsGarmaroudi FS, Marchant D, Si X, Khalili A, Bashashati A, Wong BW, Tabet A, Ng RT, Murphy K, Luo H, Janes KA, McManus BM,
JournalProc Natl Acad Sci U S A
PubMed ID20833815
'Signal transduction networks can be perturbed biochemically, genetically, and pharmacologically to unravel their functions. But at the systems level, it is not clear how such perturbations are best implemented to extract molecular mechanisms that underlie network function. Here, we combined pairwise perturbations with multiparameter phosphorylation measurements to reveal causal mechanisms ... More
Actinobacillus actinomycetemcomitans induces apoptosis in human monocytic THP-1 cells.
AuthorsKato S, Sugimura N, Nakashima K, Nishihara T, Kowashi Y,
JournalJ Med Microbiol
PubMed ID15713614
'It has previously been reported that the murine macrophage cell line J774.1 and the human oral epithelial cell line KB undergo apoptosis as a result of Actinobacillus actinomycetemcomitans infection. Recent studies have demonstrated that apoptosis regulation is modulated by multiple phosphorylation of several different protein kinases, including the major subtypes ... More
Assessment of gefitinib- and CI-1040-mediated changes in epidermal growth factor receptor signaling in HuCCT-1 human cholangiocarcinoma by serial fine needle aspiration.
AuthorsHidalgo M, Amador ML, Jimeno A, Mezzadra H, Patel P, Chan A, Nielsen ME, Maitra A, Altiok S,
JournalMol Cancer Ther
PubMed ID16891476
'One specific limitation to the clinical development of targeted cancer therapeutics is the lack of well-validated pharmacodynamic markers. Such tools might conceivably provide a framework within which to better evaluate the selection of specific molecules as therapeutic targets. Nevertheless, the practical application of this hypothesis in clinical development remains elusive. ... More
The PAXgene(®) tissue system preserves phosphoproteins in human tissue specimens and enables comprehensive protein biomarker research.
'Precise quantitation of protein biomarkers in clinical tissue specimens is a prerequisite for accurate and effective diagnosis, prognosis, and personalized medicine. Although progress is being made, protein analysis from formalin-fixed and paraffin-embedded tissues is still challenging. In previous reports, we showed that the novel formalin-free tissue preservation technology, the PAXgene ... More
Subtoxic levels hydrogen peroxide-induced production of interleukin-6 by retinal pigment epithelial cells.
AuthorsWu WC, Hu DN, Gao HX, Chen M, Wang D, Rosen R, McCormick SA
JournalMol Vis
PubMed ID21031020
To study the effect of subtoxic levels of hydrogen peroxide (H(2)O(2)) on the expression and release of interleukin-6 (IL-6) by cultured retinal pigment epithelial (RPE) cells and to explore the relevant signal pathways. ... More
Peroxynitrite-modified collagen-II induces p38/ERK and NF-kappaB-dependent synthesis of prostaglandin E2 and nitric oxide in chondrogenically differentiated mesenchymal progenitor cells.
AuthorsWhiteman M, Spencer JP, Zhu YZ, Armstrong JS, Schantz JT
JournalOsteoarthritis Cartilage
PubMed ID16427328
Peroxynitrite (ONOO(-)) is formed in the inflamed and degenerating human joint. Peroxynitrite-modified collagen-II (PMC-II) was recently discovered in the serum of patients with osteoarthritis (OA) and rheumatoid arthritis (RA). Therefore we investigated the cellular effects of PMC-II on human mesenchymal progenitor cells (MPCs) as a model of cartilage and cartilage ... More
Contribution of RhoA/Rho-kinase/MEK1/ERK1/2/iNOS pathway to ischemia/reperfusion-induced oxidative/nitrosative stress and inflammation leading to distant and target organ injury in rats.
AuthorsSari AN, Kacan M, Unsal D, Sahan Firat S, Kemal Buharalioglu C, Vezir O, Korkmaz B, Cuez T, Canacankatan N, Sucu N, Ayaz L, Tamer Gumus L, Gorur A, Tunctan B,
Journal
PubMed ID24296316
The small G protein RhoA and its downstream effector Rho-kinase play an important role in various physiopathological processes including ischemia/reperfusion (I/R) injury. Reactive oxygen and nitrogen species produced by iNOS and NADPH oxidase are important mediators of inflammation and organ injury following an initial localized I/R event. The aim of ... More
Statins inhibit growth of human endometrial stromal cells independently of cholesterol availability.
AuthorsPiotrowski PC, Kwintkiewicz J, Rzepczynska IJ, Seval Y, Cakmak H, Arici A, Duleba AJ,
JournalBiol Reprod
PubMed ID16571871
Endometriosis is characterized by ectopic growth of endometrial tissues. Statins, inhibitors of 3-hydroxy-3methylglutaryl-coenzyme A reductase (HMGCR), have been shown to decrease proliferation of several mesenchymal tissues. Actions of statins may be related to decreased availability of cholesterol as well as intermediate metabolites of the mevalonate pathway downstream of HMGCR. This ... More
Enhancement of cisplatin cytotoxicity by benzyl isothiocyanate in HL-60 cells.
AuthorsLee Y, Kim YJ, Choi YJ, Lee JW, Lee S, Chung HW,
JournalFood Chem Toxicol
PubMed ID22525867
Cis-diamminedichloroplatinum (II) (cisplatin) is one of the most widely used chemotherapeutic drugs, but its effectiveness is limited by tumor cell resistance and the severe side effects it causes. One strategy for overcoming this problem is the concomitant use of natural dietary compounds as therapeutic agents. Benzyl isothiocyanate (BITC) is a ... More
Alpha-synuclein and its disease-causing mutants induce ICAM-1 and IL-6 in human astrocytes and astrocytoma cells.
Autosomal dominant Parkinson disease (PD) is caused by duplication or triplication of the alpha-synuclein gene as well as by the A30P, E46K, and A53T mutations. The mechanisms are unknown. Reactive astrocytes in the substantia nigra of PD and MPTP-treated monkeys display high levels of the inflammatory mediator intercellular adhesion molecule-1 ... More