Exposing mice to a social stressor called social disruption (SDR) that involves repeated social defeat during intermale aggression results in increased circulating cytokines, such as interleukin-1α (IL-1α) and IL-1β, and increased reactivity of splenic CD11b(+) macrophages to inflammatory stimuli. For example, upon lipopolysaccharide stimulation, macrophages from stressor-exposed mice produce h...

AIMS High-mobility group box 1 (HMGB1) is a nuclear protein actively secreted by immune cells and passively released by necrotic cells that initiates pro-inflammatory signalling through binding to the receptor for advance glycation end-products. HMGB1 has been established as a key inflammatory mediator during myocardial infarction, but the proximal mechanisms responsible for myocardial HMGB1 ex...

Eicosanoid production is reduced when the nitric oxide (NO.) pathway is inhibited or when the inducible NO synthase gene is deleted, indicating that the NO. and arachidonic acid pathways are linked. We hypothesized that peroxynitrite, formed by the reaction of NO. and superoxide anion, may cause signaling events leading to arachidonic acid release and subsequent eicosanoid generation. Western b...

Peroxynitrite, a marker of oxidative stress, is elevated in conditions associated with vascular endothelial cell dysfunction, such as atherosclerosis, preeclampsia, and diabetes. However, the effects of peroxynitrite on endothelial cell function are not clear. The endothelium-derived enzymes nitric oxide synthase (NOS) and prostaglandin H synthase (PGHS) mediate vascular reactivity and contain ...

Apoptosis is an active process critical for the homeostasis of organisms. Enzymes of the caspase family are responsible for executing this process. We have previously shown that peroxynitrite (ONOO-), a biological product generated from the interaction of nitric oxide and superoxide, induces apoptosis of HL-60 cells. The aim of this study was to elucidate the mechanisms involved in the executio...

The aim of the present study was to investigate if hyperlipidemia interferes with the infarct size-limiting effect of postconditioning and to study the involvement of peroxynitrite in this phenomenon. Rats were fed a 2% cholesterol-enriched or normal diet for 12 wk. Infarct size by triphenyltetrazolium chloride staining was measured in hearts isolated from both groups and subjected to 30 min co...

Current understanding on the role of peroxynitrite in etiology and pathogenesis of some human diseases, such as cardio-vascular diseases, stroke, cancer, inflammation, neurodegenerative disorders, diabetes mellitus and diabetic complications has recently led to intensive investigation of peroxynitrite involvement in physiology and pathophysiology. Mechanism of cytotoxic effects of peroxynitrite...

Pretreatment with dexamethasone (Dex) was not toxic for U937 cells but caused a rapid lethal response upon subsequent exposure to otherwise nontoxic concentrations of peroxynitrite. This effect was not associated with enhanced formation of hydrogen peroxide taking place after peroxynitrite and was shown previously to play a pivotal role in the ensuing lethal response. Further analyses revealed ...

We recently described that hydrogen peroxide (H2O2) stimulates the synthesis of tetrahydrobiopterin (BH4) through the induction of the rate-limiting enzyme GTP-cyclohydrolase I (GTPCH), and increases tetrahydrobiopterin content in vascular endothelial cells. Tetrahydrobiopterin is easily oxidized by peroxynitrite (ONOO-), but not by hydrogen peroxide. The aim of this study was to determine the ...

During renal ischemia-reperfusion (I/R) injury, apoptosis has been reported as a very important contributor to final kidney damage. The determinant role of cytoskeleton derangement in the development of apoptosis has been previously reported, but a clear description of the different mechanisms involved in this process has not been yet provided. The aim of our study was to know the role of perox...