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At least 433 records · Page 24Linked to original sources
PubMed2000

Cytokine-induced nitric oxide production inhibits mitochondrial energy production and impairs contractile function in rat cardiac myocytes.

OBJECTIVES: The present study examined whether nitric oxide (NO) produced by inducible nitric oxide synthase (iNOS) can directly inhibit aerobic energy metabolism and impair cell function in interleukin (IL)-1beta,-stimulated cardiac myocytes. BACKGROUND: Recent reports have indicated that excessive production of NO induced by cytokines can disrupt cellular energy balance through the inhibition of mitochondrial respiration in a variety of cells. However, it is still largely uncertain whether the NO-induced energy depletion affects myocardial contractility. METHODS: Primary cultures of rat neonatal cardiac myocytes were prepared, and NO2-/NO3- (NOx) in the culture media was measured using Griess reagent. RESULTS: Treatment with IL-1beta (10 ng/ml) increased myocyte production of NOx in a time-dependent manner. The myocytes showed a concomitant significant increase in glucose consumption, a marked increase in lactate production, and a significant decrease in cellular ATP (adenosine 5'-triphosphate). These metabolic changes were blocked by co-incubation with N(G)-monomethyl-L-arginine (L-NMMA), an inhibitor of NO synthesis. Sodium nitroprusside (SNP), a NO donor, induced similar metabolic changes in a dose-dependent manner, but 8-bromo-cyclic guanosine 3',5'-monophosphate (8-bromo-cGMP), a cGMP donor, had no effect on these parameters. The activities of the mitochondrial iron-sulfur enzymes, NADH-CoQreductase and succinate-CoQreductase, but not oligomycin-sensitive ATPase, were significantly inhibited in the IL-1beta, or SNP-treated myocytes. Both IL-1beta and SNP significantly elevated maximum diastolic potential, reduced peak calcium current (I(Ca)), and lowered contractility in the myocytes. KT5823, an inhibitor of cGMP-dependent protein kinase, did not block the electrophysiological and contractility effects. CONCLUSIONS: These data suggest that IL-1beta-induced NO production in cardiac myocytes lowers energy production and myocardial contractility through a direct attack on the mitochondria, rather than through cGMP-mediated pathways.

Adenosine Triphosphate↗
PubMed2003

Phonological processing during language production: fMRI evidence for a shared production-comprehension network.

Studies of phonological processes during language comprehension consistently report activation of the superior portion of Broca's area. In the domain of language production, however, there is no unequivocal evidence for the contribution of Broca's area to phonological processing. The present event-related fMRI study investigated the existence of a common neural network for phonological decisions in comprehension and production by using production tasks most comparable to those previously used in comprehension. Subjects performed two decision tasks on the initial phoneme of German picture names (/b/ or not? Vowel or not?). A semantic decision task served as a baseline for both phonological tasks. The contrasts between each phonological task and the semantic task were calculated, and a conjunction analysis was performed. There was significant activation in the superior portion of Broca's area (Brodmann's area (BA) 44) in the conjunction analysis, also present in each single contrast. In addition, further left frontal (BA 45/46) and temporal (posterior superior temporal gyrus) areas known to support phonological processing in both production and comprehension were activated. The results suggest the existence of a shared fronto-temporal neural network engaged in the processing of phonological information in both perception and production.

Adult↗
PubMed1997

Mycobacterium tuberculosis (MTB)-stimulated production of nitric oxide by human alveolar macrophages and relationship of nitric oxide production to growth inhibition of MTB.

SETTING: Although nitric oxide (NO) is a major proximate mediator of microbicidal activity in murine macrophages against intracellular pathogens including mycobacteria, its production by and effector role in human macrophages is not clear. OBJECTIVE: To determine the capacity of Mycobacterium tuberculosis (MTB) to stimulate NO in human monocytes (MN) and alveolar macrophages (AM) and to assess the relationship between NO production and intracellular growth of MTB. DESIGN: NO production (measured as nitrite) by MTB (H37Ra)-infected macrophages and intracellular growth of MTB were measured in cells from 17 healthy subjects. RESULTS: MTB (5:1, MTB:cells) stimulated little to no NO by MN, but induced NO in AM at days 4 and 7 after infection. There was, however, variability in the response by AM to MTB: among seven subjects MTB-induced NO was low (4 +/- 2 microM, mean +/- SE); six subjects were moderate (56 +/- 11); four subjects were high (502 +/- 167). NO synthase inhibitors inhibited the production of NO by AM but did not significantly affect the intracellular growth of MTB, although a trend towards increased intracellular growth was seen on day 4 of culture. Intracellular growth of MTB in AM from low NO producers was significantly higher than that in AM from moderate NO producers, P < or = 0.05. Inducible NO synthase (iNOS) mRNA by RT-PCR was constitutively expressed by both MN and AM, but was further stimulated by MTB in AM > MN; MTB-induced iNOS protein was present in both MN and AM by Western blot analysis. CONCLUSION: Thus, MTB-infected human AM are capable of producing NO and NO production correlates with intracellular growth inhibition of MTB in AM suggesting that NO may serve either directly or indirectly as a mycobactericidal mediator in human tissue macrophages.

Adult↗
PubMed2001

Histamine inhibits chemotaxis, phagocytosis, superoxide anion production, and the production of TNFalpha and IL-12 by macrophages via H2-receptors.

Histamine is released from stimulated basophils and mast cells, and plays an important role in the pathogenesis of allergic inflammatory processes. In vitro treatment of macrophages with histamine resulted in inhibition of chemotaxis. Moreover, histamine at l0(-5) M markedly inhibited the production of superoxide anions by both opsonized zymosan-A and phorbol 12-myristate 13-acetate (PMA) stimulated macrophages and histamine at a concentration range of 10(-7) to 10(-5) M significantly inhibited phagocytosis of Escherichia coli by macrophages. In addition, H2-selective receptor agonist dimaprit resulted in inhibition of macrophage chemotaxis and markedly inhibited the production of superoxide anion by PMA-stimulated macrophages and phagocytosis of E. coli by macrophages. On the other hand, histamine and dimaprit both resulted in a concentration-dependent inhibition of lipopolysaccharide-induced production of TNFalpha and IL-12 by macrophages. These results suggest that histamine and dimaprit may inhibit chemotaxis, phagocytosis, superoxide anion production, and the production of TNFalpha and IL-12 by macrophages via H2-histamine receptors. reserved.

Animals↗
PubMed1999

Fast product formation and slow product release are important features in a hysteretic reaction mechanism of glutathione transferase T2-2.

The reaction mechanism of rat glutathione transferase T2-2 has been studied using pre-steady-state and steady-state kinetics. Several parts of the catalytic cycle including binding of substrates, product formation, and product release were investigated. Under saturating conditions, a two-step product release was found to be rate limiting in the enzyme-catalyzed reactions between the nucleophilic substrate glutathione and either of the two electrophilic substrates 1-menaphthyl sulfate and 4-nitrobenzyl chloride. The rate constant for pre-steady-state product formation on rat glutathione transferase T2-2 has an observed pK(a) value of 5.7 apparently due to ionization of the sulfhydryl group of glutathione. This rate constant is approximately 2 orders of magnitude higher than k(cat) at pH values of >6. It can be predicted from the pH dependence that product formation would be the sole rate-limiting step at pH values of <3. A hysteretic mechanism of rGST T2-2 is proposed based on a slow conformational transition detected in pre-steady-state displacement experiments.

Animals↗
PubMedDate not supplied

Effects of abrupt and gradual osmotic stress on antibody production and content in hybridoma cells that differ in production kinetics.

AB2-143.2 cells exhibit non-growth-associated antibody production (constant specific antibody production rate (qAb) throughout batch culture), while IND1 cells exhibit growth-associated production (decrease in qAb during stationary phase). AB2-143.2 cells increase qAb following abrupt batch osmotic stress. Enhanced antibody production in IND1 cells after batch osmotic shock is evidenced as maintenance of the higher exponential phase qAb into the stationary phase. AB2-143.2 cells also increase qAb in response to gradual osmotic stress in continuous culture. In contrast, IND1 cells decrease qAb during gradual osmotic stress. Although the two cell lines differ in antibody production, they have very similar intracellular antibody content profiles. Both show (1) constant antibody content during the exponential phase in control culture with a decrease as cells enter stationary phase; (2) maintenance of exponential-phase antibody content into the stationary phase after batch osmotic shock; and (3) no change in antibody content in response to gradual osmotic stress.

Animals↗
PubMedDate not supplied

Development of a highly productive and scalable plasmid DNA production platform.

With the applications of DNA vaccines extending from infectious diseases to cancer, achieving the most efficient, reproducible, robust, scalable, and economical production of clinical grade plasmid DNA is paramount to the medical and commercial success of this novel vaccination paradigm. A first generation production process based on the cultivation of Escherichia coli in a chemically defined medium, employing a fed-batch strategy, delivered reasonable volumetric productivities (500-750 mg/L) and proved to perform very well across a wide range of E. coli constructs upon scale-up at industrial scale. However, the presence of monosodium glutamate (MSG) in the formulation of the cultivation and feed solution was found to be a potential cause of process variability. The development of a second generation process, based on a defined cultivation medium and feed solution excluding MSG, was undertaken. Optimization studies, employing a plasmid coding for the HIV gag protein, resulted in cultivation conditions that supported volumetric plasmid titers in excess of 1.2 g/L, while achieving specific yields ranging from 25 to 32 microg plasmid DNA/mg of dry cell weight. When used for the production of clinical supplies, this novel process demonstrated applicability to two other constructs upon scale-up in 2,000-L bioreactors. This second generation process proved to be scalable, robust, and highly productive.

Bioreactors↗
PubMed2002

Effects of raw materials, ingredients, and production lines on arsenic and copper concentrations in confectionery products.

The Spaniard legislation sets up maximum levels for total arsenic (As) and copper (Cu) in confectionery products at 0.1 and 5.0 microg g(-)(1), respectively. Concentrations of these two trace elements were determined in four confectionery products: chewing gum, two licorice items, and soft candy. The effects of raw materials quality and production lines were studied. Arsenic and copper were quantified by atomic absorption spectrometry with hydride generation and slotted-tube atom trap tubes, respectively. Their levels were, in general, below the maximum limits establish by the Spaniard legislation; however, the As concentration in the licorice sticks was above this maximum limit (0.11 +/- 0.01 microg g(-)(1)). Statistics proved that quality of raw materials and the production lines both significantly affected As and Cu concentrations in the final products. The licorice extract and molasses were found as the common source for As and Cu pollution. The As concentration in the licorice extract was 0.503 +/- 0.01 microg g(-)(1), and could represent a serious hazard to human health if it is used in high proportions.

Arsenic↗
PubMed2001

Effects of specific anti-B and/or anti-plasma cell immunotherapy on antibody production in baboons: depletion of CD20- and CD22-positive B cells does not result in significantly decreased production of anti-alphaGal antibody.

Anti-Galalpha1-3Gal antibodies (antialphaGal Ab) are a major barrier to clinical xenotransplantation as they are believed to initiate both hyperacute and acute humoral rejection. Extracorporeal immunoadsorption (EIA) with alphaGal oligosaccharide columns temporarily depletes antialphaGal Ab, but their return is ultimately associated with graft destruction. We therefore assessed the ability of two immunotoxins (IT) and two monoclonal antibodies (mAb) to deplete B and/or plasma cells both in vitro and in vivo in baboons, and to observe the rate of return of antialphaGal Ab following EIA. The effects of the mouse anti-human IT anti-CD22-ricin A (proportional to CD22-IT, directed against a B cell determinant) and anti-CD38-ricin A (proportional to CD38-IT, B and plasma cell determinant) and the mouse anti-human anti-CD38 mAb (proportional to CD38 mAb) and mouse/human chimeric anti-human anti-CD20 mAb (proportional to CD20 mAb, Rituximab, B cell determinant) on B and plasma cell depletion and antialphaGal Ab production were assessed both in vitro and in vivo in baboons (n = 9) that had previously undergone splenectomy. For comparison, two baboons received nonmyeloablative whole body irradiation (WBI) (300 cGy), and one received myeloablative WBI (900 cGy). Depletion of B cells was monitored by flow cytometry of blood, bone marrow (BM) and lymph nodes (LN), staining with anti-CD20 and/or anti-CD22 mAbs, and by histology of LN. EIA was carried out after the therapy and antialphaGal Ab levels were measured daily. In vitro proportional to CD22-IT inhibited protein synthesis in the human Daudi B cell line more effectively than proportional to CD38-IT. Upon differentiation of B cells into plasma cells, however, less inhibition of protein synthesis after proportional to CD22-IT treatment was observed. Depleting CD20-positive cells in vitro from a baboon spleen cell population already depleted of granulocytes, monocytes, and T cells led to a relative enrichment of CD20-negative cells, that is plasma cells, and consequently resulted in a significant increase in antialphaGal Ab production by the remaining cells, whereas depleting CD38-positive cells resulted in a significant decrease in antialphaGal Ab production. In vivo, WBI (300 or 900 cGy) resulted in 100% B cell depletion in blood and BM, > 80% depletion in LN, with substantial recovery of B cells after 21 days and only transient reduction in antialphaGal Ab after EIA. Proportional to CD22-IT depleted B cells by > 97% in blood and BM, and by 60% in LN, but a rebound of B cells was observed after 14 and 62 days in LN and blood, respectively. At 7 days, serum antialphaGal IgG and IgM Ab levels were reduced by a maximum of 40-45% followed by a rebound to levels up to 12-fold that of baseline antialphaGal Ab by day 83 in one baboon. The results obtained with proportional to CD38-IT were inconclusive. This may have been, in part, due to inadequate conjugation of the toxin. Cell coating was 100% with proportional to CD38 mAb, but no changes in antialphaGal Ab production were observed. Proportional to CD20 mAb resulted in 100% depletion of B cells in blood and BM, and 80% in LN, with recovery of B cells starting at day 42. Adding 150cGy WBI at this time led to 100% depletion of B cells in the BM and LN. Although B cell depletion in blood and BM persisted for > 3 months, the reduction of serum antialphaGal IgG or IgM Ab levels was not sustained beyond 2 days. Proportional to CD20 mAb + WBI totally and efficiently depleted CD20- and CD22-positive B cells in blood, BM, and LN for > 3 months in vivo, but there was no sustained clinically significant reduction in serum antialphaGal Ab. The majority of antibody secretors are CD38-positive cells, but targeting these cells in vitro or in vivo with proportional to CD38-IT was not very effective. These observations suggest that CD20-and CD22-positive B cells are not the major source of antialphaGal Ab production. Future efforts will be directed towards suppression of plasma cell function.

Animals↗
PubMed1985

Mast-cell products and heparin stimulate the production of mononuclear-cell factor by cultured human monocyte/macrophages.

Purified mast cells derived from rat peritoneal fluids and dog mastocytomas were extracted with 1 M-NaCl and sonication techniques. The mast-cell products increased the production of mononuclear cell factor from human peripheral blood mononuclear cells in culture, as judged by the enhanced stimulation of prostaglandin E (2-5 fold) and collagenase (3-11-fold) production by cultured adherent synovial cells. Heparin alone (1-10 micrograms/ml) induced a similar stimulation of mononuclear-cell-factor production by monocyte cultures, whereas histamine (1-10 micrograms/ml) had no effect. The stimulatory effect of mast-cell products and heparin represented a direct effect on mononuclear cells; they did not potentiate the effect of monokine on the synovial cells. These results suggest that mast-cell-macrophage interactions may play a significant role in the pathogenesis of inflammation and connective-tissue degradation.

Cells, Cultured↗
PubMed2003

TGF-beta1 production in inflammatory bowel disease: differing production patterns in Crohn's disease and ulcerative colitis.

Transforming growth factor-beta (TGF-beta) is an inhibitory cytokine recognized as a key regulator of immunological homeostasis and inflammatory responses. TGF-beta is involved in experimental models of oral tolerance and in the pathogenesis of experimental colitis. Patients with inflammatory bowel disease (IBD) have inappropriate T cell responses to antigenic components of their own intestinal microflora, suggesting the presence of a disorder in the normal mucosal immune mechanism that ensures the down-regulation of responses to harmless constituents in the microflora. To evaluate the contribution of TGF-beta to this imbalance, we measured TGF-beta1 production by lamina propria mononuclear cells (LPMC) and T cells isolated from tissue specimens of patients with Crohn's disease (CD), ulcerative colitis (UC) and controls. Cells were cultured in the presence or absence of anti-CD2 plus anti-CD28 MoAbs and TGF-beta1 production in culture supernatants was measured by ELISA. LPMC isolated from CD patients produced significantly less TGF-beta1 than controls when stimulated via CD2 plus CD28 pathways (P = 0.001)] conversely, in UC patients increased production of TGF-beta1 compared to controls was observed (P = 0.0005). These differences were also observed with purified lamina propria (LP) T cells in both diseases and were associated with the presence of inflammation. Thus, TGF-beta1 production shows contrasting secretion in CD and in UC, probably as a consequence of the different Th polarization. The absolute or relative defect in TGF-beta1 production observed in CD and UC may contribute to the perpetuation of inflammation.

Adult↗
PubMed2002

Products from human mast cell line cells enhance the production of interferon-gamma by CD8+ and CD4+ T cells.

In patients with allergic asthma, T-cell cytokines are implicated in the regulation of the local inflammation in the airways. The ability of sensitized mast cells to release mediators and cytokines early upon allergen stimulation makes them important candidates for local immunoregulation. We have studied the effects of human mast cells on T cells with the use of the human mast cell line HMC-1. We showed that activated human mast cells or their soluble products induced and enhanced the interferon-gamma (IFN-gamma) production by T cells up to about 60-fold. The production of interleukin (IL)-4 was hardly affected and that of IL-5 was slightly enhanced. The enhancement of IFN-gamma production was induced both in polyclonal CD4+ and CD8+ T cells and in CD4+ and CD8+ T-cell clones. Further characterization of the factors involved demonstrated a molecular mass above 30 000. Our results implicate that by this mechanism mast cells may account for a negative feedback system locally down-regulating allergen-induced T helper 2 responses via IFN-gamma production by the T cells.

Adult↗
PubMed1996

Cytokine production by lymph node cells from mice infested with Ixodes ricinus ticks and the effect of tick salivary gland extracts on IL-2 production.

In BALB/c mice repeatedly infested with nymphal Ixodes ricinus ticks, lymphocytes from axillary and brachial lymph nodes which drain the tick attachment site produced significant levels of IL-2, TNF-alpha and GM-CSF when stimulated in vitro with Con A or anti-CD3 antibodies. Cytokine production by cells from lymph nodes of the opposite flank was equivalent to that of cells from uninfested mice. Nine days after the first infestation and IL-2, GM-CSF were produced primarily by the CD4+ T cells, while some other cell types contributed also to the TNF-alpha production. In mice repeatedly infested, a gradual increase of lymph node cell production of IL-2 was observed. The IL-2 levels regularly increased from the first to the third infestation compared to TNF-alpha levels which gradually decreased. The in vitro production of GM-CSF was not affected by successive infestations. Spleen lymphocytes from naive mice produced higher levels of IL-2 than lymphocytes from axillary and brachial lymph nodes. Both tick salivary gland extracts and D-mannose inhibited IL-2 production by these lymphocytes.

Animals↗
PubMed2000

Green algal extracellular products regulate antialgal toxin production in a cyanobacterium.

Many bacterial genes and virulence factors are regulated by interbacterial and/or host-parasite chemical signals. We demonstrate that toxin production by a free-living freshwater cyanobacterium is regulated in part by the presence of extracellular products of a eukaryotic green alga. In growth experiments, extracellular products made by the cyanobacterium Anabaena flos-aquae contained both anatoxin and microcystin, and significantly reduced the yield of Chlamydomonas reinhardtii, a green alga. Based on experiments in which we added purified toxins to C. reinhardtii cultures, we believe that microcystin was responsible for the growth reduction. A. flos-aquae produced anatoxin constitutively when grown alone, but anatoxin concentration increased in the presence of C. reinhardtii elicitors. Microcystin accumulation depended on the growth phase; however, high concentrations of C. reinhardtii extracellular products completely inhibited microcystin accumulation. Our results demonstrate that cyanobacterial toxin production may be regulated by complex growth phase-dependent and environmental chemical cues, and suggest that secreted chemicals can mediate the outcome of competition between the cyanobacterium A. flos-aquae and the green alga C. reinhardtii.

Anabaena↗
PubMed2003

Effects of thyroid state on H2O2 production by rat heart mitochondria: sites of production with complex I- and complex II-linked substrates.

This work was designed to determine possible effects of altered thyroid states on rates and sites of H 2 O 2 production by rat heart mitochondria. Rates of O 2 consumption and H 2 O 2 release, capacities to remove the peroxide, lipid peroxidation, cytochrome oxidase activities and ubiquinone levels were determined in heart mitochondria from euthyroid, hypothyroid, and hyperthyroid rats. Hypothyroidism decreased, whereas hyperthyroidism increased the rates of O 2 consumption and H 2 O 2 release during both state 4 and state 3 respiration with Complex I- or Complex II-linked substrates. The percentage of O 2 released as H 2 O 2 was not significantly affected by thyroid state. However, the mitochondrial capacity to remove H 2 O 2 increased in the transition from hypothyroid to hyperthyroid state, which indicates that H 2 O 2 production did not modify in proportion to the rate of O 2 consumption. The thyroid-state-linked changes in H 2 O 2 production were well correlated with the levels of hydroperoxides. Rates of H 2 O 2 release in the presence of respiratory inhibitors indicated that changes in the H 2 O 2 production occurred at both sites at which H 2 O 2 was generated in euthyroid state. This result and the observation that ubiquinol levels and cytochrome oxidase activities increase in the transition from hypothyroid to hyperthyroid state suggest that the modifications of H 2 O 2 production are due to a modulation by thyroid hormone of mitochondrial content of autoxidisable electron carriers.

Animals↗
PubMed2003

Engineering the metabolism of Escherichia coli W3110 for the conversion of sugar to redox-neutral and oxidized products: homoacetate production.

Microbial processes for commodity chemicals have focused on reduced products and anaerobic conditions where substrate loss to cell mass and CO(2) are minimal and product yields are high. To facilitate expansion into more oxidized chemicals, Escherichia coli W3110 was genetically engineered for acetate production by using an approach that combines attributes of fermentative and oxidative metabolism (rapid growth, external electron acceptor) into a single biocatalyst. The resulting strain (TC36) converted 333 mM glucose into 572 mM acetate, a product of equivalent oxidation state, in 18 h. With excess glucose, a maximum of 878 mM acetate was produced. Strain TC36 was constructed by sequentially assembling deletions that inactivated oxidative phosphorylation (deltaatpFH), disrupted the cyclic function of the tricarboxylic acid pathway (deltasucA), and eliminated native fermentation pathways (deltafocA-pflB deltafrdBC deltaldhA deltaadhE). These mutations minimized the loss of substrate carbon and the oxygen requirement for redox balance. Although TC36 produces only four ATPs per glucose, this strain grows well in mineral salts medium and has no auxotrophic requirement. Glycolytic flux in TC36 (0.3 micromol.min(-1).mg(-1) protein) was twice that of the parent. Higher flux was attributed to a deletion of membrane-coupling subunits in (F(1)F(0))H(+)-ATP synthase that inactivated ATP synthesis while retaining cytoplasmic F(1)-ATPase activity. The effectiveness of this deletion in stimulating flux provides further evidence for the importance of ATP supply and demand in the regulation of central metabolism. Derivatives of TC36 may prove useful for the commercial production of a variety of commodity chemicals.

Acetates↗
PubMed1999

Activation of stress signaling pathways by the end product of lipid peroxidation. 4-hydroxy-2-nonenal is a potential inducer of intracellular peroxide production.

In the present study, we studied the signal transduction mechanism that is involved in the expression of c-Jun protein evident after exposure of rat liver epithelial RL34 cells to the major end product of oxidized fatty acid metabolism, 4-hydroxy-2-nonenal (HNE). HNE treatment of the cells resulted in depletion of intracellular glutathione (GSH) and in the formation of protein-bound HNE in plasma membrane. In addition, HNE strongly induced intracellular peroxide production, suggesting that HNE exerted oxidative stress on the cells. Potent expression of c-Jun occurred within 30 min of HNE treatment, which was accompanied by a time-dependent increase in activator protein-1 (AP-1) DNA binding activity. We found that HNE caused an immediate increase in tyrosine phosphorylation in RL34 cells. In addition, HNE strongly induced phosphorylation of c-Jun N-terminal kinases (JNK) and p38 mitogen-activated protein kinases and also moderately induced phosphorylation of extracellular signal-regulated kinases. The phosphorylation of JNK was accompanied by a rapid and transient increase in JNK and p38 activities, whereas changes in the activity of extracellular signal-regulated kinase were scarcely observed. GSH depletion by L-buthionine-S, R-sulfoximine, a specific inhibitor of GSH biosynthesis, only slightly enhanced peroxide production and JNK activation, suggesting that HNE exerted these effects independent of GSH depletion. This and the findings that (i) HNE strongly induced intracellular peroxide production, (ii) HNE-induced JNK activation was inhibited by pretreatment of the cells with a thiol antioxidant, N-acetylcysteine, and (iii) H2O2 significantly activated JNK support the hypothesis that pro-oxidants play a crucial role in the HNE-induced activation of stress signaling pathways. In addition, we found that, among the inhibitors of tyrosine kinases, cyclooxygenase, and Ca2+ influx, only quercetin exerted a significant inhibitory effect on HNE-induced JNK activation. In light of the JNK-dependent induction of c-jun transcription and the AP-1-induced transcription of xenobiotic-metabolizing enzymes, these data may show a potential critical role for JNK in the induction of a cellular defense program against toxic products generated from lipid peroxidation.

Aldehydes↗
PubMed2003

Towards sustainable production of protein-rich foods: appraisal of eight crops for Western Europe. PART II: Analysis of the technological aspects of the production chain.

Increased production of plant protein is required to support the production of protein-rich foods which can replace meat in the human diet to reduce the strain that intensive animal husbandry poses on the environment. The suitability of lupin (Lupinus spp.), pea (Pisum sativum), quinoa (Chenopodium quinoa Willd.), triticale (x Triticosecale), lucerne (Medicago sativa), grasses (Lolium and Festuca spp.), rapeseed/canola (Brassica napus) and potato (Solanum tuberosum) for protein production in Western Europe was studied on the basis of a chain-approach. The technological aspects, which are considered in this paper, are the processing methods, and the functional and nutritional properties of the derived protein products. The overall evaluation of the technological prospects of the eight crops as a protein source for Western Europe leads to the conclusion that this part of the production chain is not decisive for that choice. Pea and lupin have a slight advantage over the other crops, because their concentrates and isolates are already commercially available.

Agriculture↗