Reactive nitrogen species-induced cell death requires Fas-dependent activation of c-Jun N-terminal kinase.

Nitrogen dioxide is a highly toxic reactive nitrogen species (RNS) recently discovered as an inflammatory oxidant with great potential to damage tissues. We demonstrate here that cell death by RNS was caused by c-Jun N-terminal kinase (JNK). Activation of JNK by RNS was density dependent and caused mitochondrial depolarization and nuclear condensation.

Baculovirus P35 inhibits NO-induced apoptosis in activated macrophages by inhibiting cytochrome c release.

The baculovirus protein P35 inhibits apoptosis in a diverse range of animals such as insects, nematodes and mammals. Evidence suggests that P35 can inhibit members of caspase family proteases that are key mediators of mammalian apoptosis. We demonstrate that p35 inhibits activation-induced nitric oxide (NO)-mediated apoptosis in the RAW 264.

Dynamic regulation of Src-family kinases by CD45 in B cells.

CD45 is a key protein tyrosine phosphatase regulating Src-family protein tyrosine kinases (Src-PTKs) in lymphocytes; precisely how it exerts its effect remains controversial, however. We previously demonstrated that CD45 negatively regulates Lyn in the WEHI-231 B-cell line. Here we show that negative regulation by CD45 is physiologically significant in B cells and that some CD45 is constitutively associated with glycolipid-enriched microdomains (GEMs), where it inhibits Src-PTKs by dephosphorylating both the negative and the positive regulatory sites.

Eosinophil peroxidase catalyzes JNK-mediated membrane blebbing in a Rho kinase-dependent manner.

Eosinophilic influx is characteristic of numerous inflammatory conditions. Eosinophil peroxidase (EPO) is a major enzyme present in eosinophils and upon degranulation, becomes released into the airways of asthmatics. As a result of its cationic nature and its ability to catalyze the formation of highly toxic oxidants, EPO has significant potential to induce cellular injury.

Hydrogen peroxide signaling through tumor necrosis factor receptor 1 leads to selective activation of c-Jun N-terminal kinase.

Binding of tumor necrosis factor-alpha (TNFalpha) to its receptor, TNF-R1, results in the activation of inhibitor of kappaB kinase (IKK) and c-Jun N-terminal kinase (JNK) pathways that are coordinately regulated and important in survival and death. We demonstrated previously that in response to hydrogen peroxide (H2O2), the ability of TNFalpha to activate IKK in mouse lung epithelial cells (C10) was inhibited and that H2O2 alone was sufficient to activate JNK and induce cell death. In the current study, we investigated the involvement of TNF-R1 in H2O2-induced JNK activation.

Reactive nitrogen species and cell signaling: implications for death or survival of lung epithelium.

Reactive nitrogen species such as nitric oxide, peroxynitrite, and nitrogen dioxide have been implicated in the pathophysiology of inflammatory lung diseases. Yet, the molecular mechanisms and cell signaling events responsible for cellular injury remain to be elucidated. Two major signaling pathways, co-ordinately regulated and responsible for cell survival and cell death, involve nuclear factor kappa B and c-Jun-N-terminal kinase, respectively.