Nitric oxide and promotion of cardiac myocyte apoptosis

The removal of damaged, superfluous or energy-starved cells is essential for biological homeostasis, and occurs in every tissue type. Programmed cell death occurs through several closely regulated signal pathways, including apoptosis, in which cell components are broken down and packaged into small membrane-bound fragments that are then removed by neighbouring cells or phagocytes. This process is activated in the cardiac myocyte in response to a variety of stresses, including oxidative and nitrosative stress, and involves mitochondria-derived signals. Loss of cardiac myocytes through apoptosis has been shown to induce cardiomyopathy in a variety of gene-targeted animal models. Because cardiac myocytes have strictly limited ability to regenerate, sustained programmed cell death is likely to contribute to the development and progression of heart failure in a variety of myocardial diseases. At the same time, the cardiac myocyte possesses a number of mechanisms for defence against short-term haemodynamic and oxidative stresses. Our laboratory has recently examined the role of nitric oxide (NO) as a regulator of the programmed death of cardiac myocytes, and the potential contribution of NO and NO-dependent signalling to the loss of myocytes in heart failure. We will review the role of c-Jun N-terminal kinase in response to oxidative and nitrosative stress, and summarise evidence for its role as a cytoprotective mechanism. We will also review evidence implicating NO in the pathophysiology of heart failure, in the context of the extensive and sometimes contradictory body of research on NO and cell survival. (Mol Cell Biochem 263: 35–53, 2004)     

Cardiovascular Effects of Peritoneal Insufflation of Carbon Dioxide for Laparoscopy

We have investigated, in 13 artificially ventilated and anaesthetized patients, the cardiovascular effects of peritoneal insufflation of carbon dioxide preparatory to laparoscopy. Stepwise increases of intra-abdominal pressure up to a maximum of 25 cm H₂O were accompanied by increases of airway pressure, intrathoracic pressure, central venous pressure, and femoral venous pressure and by signs of cardiovascular stimulation with mild tachycardia and hypertension. End-tidal carbon dioxide tension rose only slightly. The anaesthetic technique used provided good surgical conditions; our results suggest that it does not impose undue strain on the homoeostatic ability of the patient''s cardiovascular system.     

Mouse Receptor Interacting Protein 3 Does Not Contain a Caspase-Recruiting or a Death Domain but Induces Apoptosis and Activates NF-κB

The death domain-containing receptor superfamily and their respective downstream mediators control whether or not cells initiate apoptosis or activate NF-kappaB, events critical for proper immune system function. A screen for upstream activators of NF-kappaB identified a novel serine-threonine kinase capable of activating NF-kappaB and inducing apoptosis. Based upon domain organization and sequence similarity, this novel kinase, named mRIP3 (mouse receptor interacting protein 3), appears to be a new RIP family member. RIP, RIP2, and mRIP3 contain an N-terminal kinase domain that share 30 to 40% homology. In contrast to the C-terminal death domain found in RIP or the C-terminal caspase-recruiting domain found in RIP2, the C-terminal tail of mRIP3 contains neither motif and is unique. Despite this feature, overexpression of the mRIP3 C terminus is sufficient to induce apoptosis, suggesting that mRIP3 uses a novel mechanism to induce death. mRIP3 also induced NF-kappaB activity which was inhibited by overexpression of either dominant-negative NIK or dominant-negative TRAF2. In vitro kinase assays demonstrate that mRIP3 is catalytically active and has autophosphorylation site(s) in the C-terminal domain, but the mRIP3 catalytic activity is not required for mRIP3 induced apoptosis and NF-kappaB activation. Unlike RIP and RIP2, mRIP3 mRNA is expressed in a subset of adult tissues and is thus likely to be a tissue-specific regulator of apoptosis and NF-kappaB activity. While the lack of a dominant-negative mutant precludes linking mRIP3 to a known upstream regulator, characterizing the expression pattern and the in vitro functions of mRIP3 provides insight into the mechanism(s) by which cells modulate the balance between survival and death in a cell-type-specific manner.     

Ancestral variation and the potential for genetic accommodation in larval amphibians: implications for the evolution of novel feeding strategies

SUMMARY Few studies provide empirical evidence for phenotypic plasticity's role in the evolution of novel traits. One way to do so is to test whether latent plasticity is present in an ancestor that can be refined, enhanced, or diminished by selection in derived taxa (through "genetic accommodation"), thereby producing novel traits. Here, we evaluated whether gut plasticity preceded and promoted the evolution of a novel feeding strategy in spadefoot toad tadpoles. We studied Scaphiopus couchii , whose tadpoles develop an elongate gut and consume only detritus, and two derived species, Spea multiplicata and Sp. bombifrons , whose tadpoles also express a novel, short-gut phenotype in response to a novel resource (anostracan shrimp). Consistent with the expectations of plasticity-mediated trait evolution, we found that shrimp induced a range of phenotypes in Scaphiopus that were not produced with detritus. This plasticity was either suppressed or exaggerated in Spea depending on whether the induced phenotypes were adaptive. Moreover, in contrast to its effects on morphology, shrimp induced little or no functional plasticity, as assessed by gut cell proliferation, in Scaphiopus . Shrimp did, however, induce substantial proliferation in Sp. bombifrons , the species that consumes the most shrimp and that produces the short-gut phenotype the most frequently. Thus, if Spea had ancestral morphological plasticity in response to a novel diet, their shrimp-induced short-gut morphology may have undergone subsequent genetic accommodation that improved its functionality. Hence, diet-induced phenotypic plasticity may have preceded and even promoted the evolution of a novel phenotype.     

Maternally derived testosterone and 17beta-estradiol in the eggs of Arctic-breeding glaucous gulls in relation to persistent organic pollutants

It is largely unknown if and how persistent organic pollutants (POPs) affect the transfer of maternal hormones to eggs. This occurs despite an increasing number of studies relating environmental conditions experienced by female birds at the time of egg formation to maternal hormonal effects. Here we report the concentrations of maternal testosterone, 17beta-estradiol and major classes of POPs (organochlorines, brominated flame retardants and metabolically-derived products) in the yolk of unincubated, third-laid eggs of the glaucous gull (Larus hyperboreus), a top-predator in the Arctic marine environment. Controlled for seasonal and local variation, positive correlations were found between the concentrations of certain POPs and testosterone. Contaminant-related changes in the relative concentrations of testosterone and 17beta-estradiol were also observed. In addition, yolk steroid concentrations were associated with contaminant profiles describing the proportions of different POPs present in the yolk. Eggs from nests in which two sibling eggs hatched or failed to hatch differed in POP profiles and in the relative concentrations of testosterone and 17beta-estradiol. Although the results of this correlative study need to be interpreted with caution, they suggest that contaminant-related changes in yolk steroids may occur, possibly affecting offspring performance over and above toxic effects brought about by POPs in eggs.     

Flux balance analysis of primary metabolism in Chlamydomonas reinhardtii

Background  

Photosynthetic organisms convert atmospheric carbon dioxide into numerous metabolites along the pathways to make new biomass. Aquatic photosynthetic organisms, which fix almost half of global inorganic carbon, have great potential: as a carbon dioxide fixation method, for the economical production of chemicals, or as a source for lipids and starch which can then be converted to biofuels. To harness this potential through metabolic engineering and to maximize production, a more thorough understanding of photosynthetic metabolism must first be achieved. A model algal species, C. reinhardtii, was chosen and the metabolic network reconstructed. Intracellular fluxes were then calculated using flux balance analysis (FBA).