1,720,976 research outputs found
Th1 and Th2 cytokines exert regulatory effects upon islet microvascular areas in the NOD mouse
No full textMultiple low-dose and single high-dose treatments with streptozotocin do not generate nitric oxide
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Administration of a nitric oxide synthase inhibitor does not suppress low-dose streptozotocin-induced diabetes in mice
No full textAdhesion molecules and microvascular changes in the nonobese diabetic (NOD) mouse pancreas. An NO-inhibitor (L-NAME) is unable to block adhesion inflammation-induced activation
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A lentiviral vector with a short troponin-I promoter for tracking cardiomyocyte differentiation of human embryonic stem cells.
No full textHuman embryonic stem cells (hESCs) may become important for cardiac repair due to their potentially unlimited ability to generate cardiomyocytes (CMCs). Moreover, genetic manipulation of hESC-derived CMCs would be a very promising technique for curing myocardial disorders. At the present time, however, inducing the differentiation of hESCs into CMCs is extremely difficult and, therefore, an easy and standardizable technique is needed to evaluate differentiation strategies. Vectors driving cardiac-specific expression may represent an important tool not only for monitoring new cardiac-differentiation strategies, but also for the manipulation of cardiac differentiation of ESCs. To this aim, we generated cardiac-specific lentiviral vectors (LVVs) in which expression is driven by a short fragment of the cardiac troponin-I proximal promoter (TNNI3) with a human cardiac alpha-actin enhancer, and tested its suitability in inducing tissue-specific gene expression and ability to track the CMC lineage during differentiation of ESCs. We determined that (1) TNNI3-LVVs efficiently drive cardiac-specific gene expression and mark the cardiomyogenic lineage in human and mouse ESC differentiation systems (2) the cardiac alpha-actin enhancer confers a further increase in gene-expression specificity of TNNI3-LVVs in hESCs. Although this technique may not be useful in tracking small numbers of cells, data suggested that TNNI3-based LVVs are a powerful tool for manipulating human ESCs and modifying hESC-derived CMCs
TNF-alpha signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF-alpha receptor.
No full textTNF-α signal transduction in rat neonatal cardiac myocytes: definition of pathways generating from the TNF-α receptor.
No full textCardiomyocyte hypertrophy and apoptosis
have been implicated in the loss of contractile
function during heart failure (HF). Moreover, patients
with HF have been shown to exhibit increased levels of
tumor necrosis factor (TNF-) in the myocardium.
However, the multiple signal transduction pathways
generating from the TNF- receptor in cardiomyocytes
and leading preferentially to apoptosis or hypertrophy
are still unknown. Here we demonstrate in neonatal rat
cardiomyocytes that 1) TNF- induces phosphorylation
of AKT, activation of NF-B, and the phosphorylation
of JUN kinase; 2) blocking AKT activity prevents NF-B
activation, suggesting a role for AKT in regulating
NF-B function; 3) AKT and JUN are both critical for
the hypertrophic effects of TNF-, since dominantnegative
mutants of these genes are capable of inhibiting
TNF--induced ANF-promoter up-regulation and
increase in cardiomyocyte cell size, and 4) blocking
NF-B, AKT, or JUN alone or in combination does not
sensitize cardiomyocytes to the proapoptotic effects of
TNF-, in contrast to other cell types, suggesting a
cardiac-specific pathway regulating the anti-apoptotic
events induced by TNF-. Altogether, the data presented
evidence the role of AKT and JUN in TNF--
induced cardiomyocyte hypertrophy and apoptosi
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