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15-Hydroxyeicosatetraenoic acid (15-HETE), a metabolic product of arachidonic acid (AA), plays an important role in pulmonary vascular smooth muscle remodeling. Although its effects on the apoptotic responses are known, the underlying mechanisms are still poorly understood. Since Akt is a critical regulator of cell survival and vascular remodeling, there may be a crosstalk between 15-HETE anti-apoptotic process and PI3K/Akt survival effect in rat pulmonary arterial smooth muscle cells (PASMCs). To test this hypothesis, we studied the effect of 15-HETE on cell survival and apoptosis using Western blot, cell viability measurement, nuclear morphology determination, TUNEL assay and mitochondrial potential analysis. We found that activation of the PI3K/Akt signaling system was necessary for the 15-HETE to suppress PASMC apoptosis and improve cell survival. Our results indicated that 15-HETE inhibited the apoptotic responses of PASMCs, including morphological alterations, mitochondrial depolarization and the expression apoptosis-specific proteins. These effects were likely to be mediated through the activation of PI3K/Akt. Two downstream signal molecules of PI3K/Akt were identified. Both FasL and Bad were down-regulated by 15-HETE and 15-HETE phosphorylated Bad. These changes depended on the PI3K/Akt signaling pathway in PASMCs. Thus a signal transduction pathway was demonstrated which is necessary for the effects of 15-HETE in protection PASMCs from apoptosis.

N-Arachidonoyl dopamine (NADA) is an endogenous lipid that modulates signal transduction in neuronal and immune pathways. NADA activates the non-selective cation channel, transient receptor potential vanilloid type 1 (TRPV(1)) and cannabinoid receptor 1. That NADA is comprised of an arachidonic acid (AA) backbone suggests that it may be metabolized through many of the enzymes that act upon AA such as the other AA-derived signaling lipids, the endogenous cannabinoids. To investigate the metabolism of NADA through the cytochrome P450 (CYP450) metabolic pathway, we studied the in vitro rat liver microsomal production of hydroxylated metabolites and their activity at recombinant human TRPV(1) receptors. We showed that following microsomal activation in the presence of NADA, omega and (omega-1) hydroxylated metabolites (19- and 20-HETE-DA) were formed. These metabolites were active at recombinant human TRPV(1) receptors, inducing a dose-dependent calcium influx. Both metabolites exhibited lower potency compared to NADA. We conclude that CYP450 enzymes are capable of metabolizing this signaling lipid forming a larger family of potential neuromodulators.

One of the best-kept secrets by fungi especially yeast is the function of the different shapes and surface structures of their vegetative and sexual cells. They definitely do not produce these shapes (e.g. round, elongated, kidney, needle, hat, saturnoid, etc.) and surfaces (e.g. smooth, rough, hairy, warty, etc.) for our curiosity or to be classified, but surely produce these for their own benefit. This mini-review will show that a large variety of 3-hydroxy oxylipins are widely distributed in the fungal domain and closely associated with these surface ornamentations. In concert with nano-scale surface structures, they probably play a role in cell aggregation as well as spore release from sexual structures such as asci.

Lipoxins (LX) are trihydroxytetraene-containing eicosanoids that are generated within the vascular lumen during platelet-leukocyte interactions and at mucosal surfaces via leukocyte-epithelial cell interactions. Recent findings have given several new concepts that are reviewed here regarding the generation of LX and 15 epi-LX and their impact in the resolution of acute inflammation and organ protection from leukocyte-mediated injury. During cell-cell interactions, transcellular biosynthetic pathways are used as major LX biosynthetic routes, and thus, in humans, LX are formed in vivo during multicellular responses such as inflammation, and asthma. This branch of the eicosanoid cascade generates specific tetraene-containing products that serve as neutrophil "stop signals," in that they regulate key steps in leukocyte trafficking and prevent neutrophil-mediated acute tissue injury. In addition, aspirin's mechanism of action also involves the triggering of carbon 15 epimers of lipoxins or 15-epi-lipoxins that mimic the bioactions of native LX. An overview of these recent developments is presented with a focus on the cellular and molecular interactions of these novel anti-inflammatory lipid mediators that also appear to facilitate the resolution of acute inflammatory responses.