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PubMed1991

Analysis of the ATPase subassembly which initiates processive DNA synthesis by DNA polymerase III holoenzyme.

The gamma complex (gamma delta delta' chi psi) subassembly of DNA polymerase III holoenzyme transfers the beta subunit onto primed DNA in a reaction which requires ATP hydrolysis. Once on DNA, beta is a "sliding clamp" which tethers the polymerase to DNA for highly processive synthesis. We have examined beta and the gamma complex to identify which subunit(s) hydrolyzes ATP. We find the gamma complex is a DNA dependent ATPase. The beta subunit, which lacks ATPase activity, enhances the gamma complex ATPase when primed DNA is used as an effector. Hence, the gamma complex recognizes DNA and couples ATP hydrolysis to clamp beta onto primed DNA. Study of gamma complex subunits showed no single subunit contained significant ATPase activity. However, the heterodimers, gamma delta and gamma delta', were both DNA-dependent ATPases. Only the gamma delta ATPase was stimulated by beta and was functional in transferring the beta from solution to primed DNA. Similarity in ATPase activity of DNA polymerase III holoenzyme accessory proteins to accessory proteins of phage T4 DNA polymerase and mammalian DNA polymerase delta suggests the basic strategy of chromosome duplication has been conserved throughout evolution.

Adenosine Triphosphatases↗
PubMed1986

Relationship between the tuberculin-type and Jones-Mote-type hypersensitivities: suppression of basophil infiltration by mycobacterial adjuvant.

Guinea-pigs immunized with bovine gammaglobulin (BGG) in incomplete Freund's adjuvant (IFA) showed the typical Jones-Mote-type hypersensitivity (JMH) reaction when tested 5 days later. This is characterized by prominent basophil infiltration. After pretreatment with complete Freund's adjuvant (CFA) 16 days before immunization with BGG in IFA, the lesions resembled the JMH reaction macroscopically in their evolution over time and in the absence of a positive macrophage migration inhibition (MIT) test. However, histologically, the lesions resembled classical tuberculin-type hypersensitivity with prominent mononuclear cell infiltration without any basophils. The pretreated animals, which failed to show basophil infiltration, were able to transfer JMH reactions with basophil infiltration into normal animals. In contrast, pretreatment of recipients with CFA or Corynebacterium parvum prevented the passive transfer of the characteristic effect on the JMH reaction when given shortly before skin testing. We postulate that macrophages activated by CFA may play an important role in regulating basophil infiltration in the effector phase of the delayed hypersensitivity reaction.

Animals↗
PubMed1991

Dual start motif in two lambdoid S genes unrelated to lambda S.

The lysis gene region of phage 21 contains three overlapping reading frames, designated S21, R21, and Rz21 on the basis of the analogy with the SRRz gene cluster of phage lambda. The 71-codon S21 gene complements lambda Sam7 for lysis function but shows no detectable homology with S lambda in the amino acid or nucleotide sequence. A highly related DNA sequence from the bacteriophage PA-2 was found by computer search of the GenBank data base. Correction of this sequence by insertion of a single base revealed another 71-codon reading frame, which is accordingly designated the SPA-2 gene and is 85% identical to S21. There are thus two unrelated classes of S genes; class I, consisting of the homologous 107-codon S lambda and 108-codon P22 gene 13, and class II, consisting of the 71-codon S21 and SPA-2 genes. The codon sequence Met-Lys-(X)-Met...begins all four genes. The two Met codons in S lambda and 13 have been shown to serve as translational starts for distinct polypeptide products which have opposing functions: the shorter polypeptide serves as the lethal lysis effector, whereas the longer polypeptide acts as a lysis inhibitor. To test whether this same system exists in the class II S genes, the Met-I and Met-4 codons of S21 were altered in inducible plasmid clones and the resultant lysis profiles were monitored. Elimination of the Met-1 start results in increased toxicity, and lysis, although not complete, begins earlier, which suggests that both starts are used in the scheduling of lysis by S21 and is consistent with the idea that the 71- and 68-residue products act as a lysis inhibitor and a lysis effector, respectively. In addition, the R gene of 21 was shown to be related to P22 gene 19, which encodes a true lysozyme activity, and was also found to be nearly identical to PA-2 ORF2. We infer that the 21 and PA-2 R genes both encode lysozymes in the T4 e gene family. These three genes form a second class lambdoid R genes, with the lambda R gene being the sole member of the first class. The existence of two interchangeable but unrelated classes of S genes and R genes is discussed in terms of a model of bacteriophage evolution in which the individual gene is the unit of evolution.

Amino Acid Sequence↗
PubMed1995

CD8-depleted donor lymphocyte infusion as treatment for relapsed chronic myelogenous leukemia after allogeneic bone marrow transplantation.

Donor lymphocyte infusions can reinduce complete remission in the majority of patients with chronic myelogenous leukemia (CML) who relapse into chronic phase after allogeneic bone marrow transplantation (BMT). Such infusions are associated with a high incidence of graft-versus-host disease (GVHD) and marrow aplasia. BMT using selective depletion of CD8+ lymphocytes from donor cells reduces the incidence of GVHD without an increase in leukemia relapse. We hypothesized that infusion of CD8-depleted donor peripheral blood lymphocytes could also reinduce complete remissions with a lesser potential to produce symptomatic GVHD in patients with CML who relapsed after allogeneic BMT. Ten patients with Ph(+) CML who relapsed a median of 353 days after BMT (range, 82 to 1,096 days) received donor lymphocyte infusions depleted of CD8+ cells. Nine patients received a single infusion and 1 received two infusions. Four patients were treated while in chronic phase with clonal evolution, 2 during accelerated phase, 3 during blast crisis, and 1 in a cytogenetic relapse. A mean of 0.9 +/- 0.3 x 10(8) mononuclear cells/kg were infused, containing 0.6 +/- 0.4 x 10(6) CD3+CD8+ cells/kg. Six patients achieved hematologic and cytogenetic remission at 4, 8, 11, 15, 39, and 54 weeks after lymphocyte infusion. Two patients developed > or = grade II acute GVHD, and 1 patient developed mild chronic GVHD. We conclude that donor lymphocyte infusions depleted of CD8+ cells can induce remissions with a low rate of severe acute GVHD in patients with CML who relapse after allogeneic BMT, supporting the hypothesis that CD8+ lymphocytes are important effectors of GVHD, but may not be essential for the graft-versus-leukemia effect against this disease. Further controlled studies are required to confirm these preliminary observations.

Acute Disease↗
PubMed1987

Control of flux through the citric acid cycle and the glyoxylate bypass in Escherichia coli.

The glyoxylate bypass and citric acid cycle operate concurrently in Escherichia coli when acetate is the sole source of carbon and energy to sustain aerobic growth. The overall carbon balance allows fluxes through the central metabolic pathways (CMPs) to be computed on the assumption that these metabolic pathways are known. Acetate is fluxed via the CMPs to the precursors required for synthesis of new biomass and also to generate the reducing power and ATP required to convert these precursors to biomass. Under these circumstances, a junction is created at isocitrate where isocitrate lyase (ICL) and isocitrate dehydrogenase (ICDH) compete for their common substrate. In general, flux through ICL generates the precursors used for biosynthesis while the larger part of the flux (95%) through ICDH is dedicated to the supply of reducing power and ATP. The system sustains a large intracellular pool of isocitrate to accommodate the rather low affinity of ICL for this substrate. Excessive flux of isocitrate through ICDH is prevented by regulation of ICDH activity: reversible inactivation of ICDH is achieved by a bifunctional kinase/phosphatase, as the phosphorylated form of ICDH has no activity. The kinase/phosphatase responds to two classes of effectors--intermediates of the CMPs generated by flux through ICL and the lower energy forms of ATP and NADPH (ADP, AMP and NADP+) generated when these intermediates are used for biosynthesis. The effect is to adjust flux through ICDH so that the rate of supply of NADPH and ATP is equal to the demands of biosynthesis. Biosynthetic fluxes are limited by the rate of supply of precursors which depends on flux through ICL. Growth rate is most likely limited by the primary flux of acetate to acetyl-CoA or flux through ICL. In the steady state, the flux through ICDH is regulated to be twice the throughput of ICL. The evolution of this complex pattern of control may have depended on alternatives to the citric acid for energy generation.

Acetates↗
PubMed1981

Design of glycolysis.

The design of the glycolytic pathway resulting from the continuous refinement of evolution is discussed with regard to three aspects. 1. Functional and structural properties of individual enzymes. The catalytic constants of the glycolytic enzymes are remarkably optimized; the turnover numbers are within one order of magnitude. The same is true for the molarities of catalytic centres in the cytosol, as is noted for yeast. Functional properties of the enzymes are reflected in their tertiary and quaternary structures. 2. Regulatory mechanisms of single enzymes. A classification of the various types of enzymic control mechanisms operating in the glycolytic pathway is given. In addition to the usual Michaelis-Menten saturation kinetics and the various types of inhibition there is control by positive and negative effectors based on oligomeric structures (fast acting, fine control) as well as regulation by chemical interconversion structures (fast acting, fine control) as well as regulation by chemical based on enzymes cascades (slow acting, very effective). 3. Functional and regulatory mechanisms of the whole glycolytic reaction pathway. A prominent feature is the high enzyme:substrate ratio, which guarantees fast response times. However, a quantitative treatment of the overall kinetics is limited by an incomplete knowledge of the enzymes' dynamic and chemical compartmentation as well as some of their control properties. From an analysis of the oscillatory state, certain control points in the glycolytic chain can be located that coincide with major branching points to other metabolic pathways. These points are controlled by fast-acting cooperative enzymes that operate in a flip-flop mechanism together with the respective antagonistic enzymes, preventing futile cycles. The gating enzymes leading to the glycogen store and the citric acid cycle are of the slow-acting but very effective interconvertible type. The combination of all the complex and intricate features of design yields a glycolytic network that enables the cell to respond to its various metabolic needs quickly, effectively and economically.

Animals↗
PubMed1989

Mammalian genes coordinately regulated by growth arrest signals and DNA-damaging agents.

More than 20 different cDNA clones encoding DNA-damage-inducible transcripts in rodent cells have recently been isolated by hybridization subtraction (A. J. Fornace, Jr., I. Alamo, Jr., and M. C. Hollander, Proc. Natl. Acad. Sci. USA 85:8800-8804, 1988). In most cells, one effect of DNA damage is the transient inhibition of DNA synthesis and cell growth. We now show that five of our clones encode transcripts that are increased by other growth cessation signals: growth arrest by serum reduction, medium depletion, contact inhibition, or a 24-h exposure to hydroxyurea. The genes coding for these transcripts have been designated gadd (growth arrest and DNA damage inducible). Two of the gadd cDNA clones were found to hybridize at high stringency to transcripts from human cells that were induced after growth cessation signals or treatment with DNA-damaging agents, which indicates that these responses have been conserved during mammalian evolution. In contrast to results with growth-arrested cells that still had the capacity to grow after removal of the growth arrest conditions, no induction occurred in HL60 cells when growth arrest was produced by terminal differentiation, indicating that only certain kinds of growth cessation signals induce these genes. All of our experiments suggest that the gadd genes are coordinately regulated: the kinetics of induction for all five transcripts were similar; in addition, overexpression of gadd genes was found in homozygous deletion c14CoS/c14CoS mice that are missing a small portion of chromosome 7, suggesting that a trans-acting factor encoded by a gene in this deleted portion is a negative effector of the gadd genes. The gadd genes may represent part of a novel regulatory pathway involved in the negative control of mammalian cell growth.

Amino Acid Sequence↗
PubMed1991

Glucose: a more powerful modulator of fructose 2,6-bisphosphate levels than insulin in human hepatocytes.

This study provides the first experimental evidence of the short-term control of fructose 2,6-bisphosphate (Fru(2,6)P2) levels in adult human hepatocytes. (1) In hepatocytes whose metabolic status resembles the fed state (glycogen-rich), exposure to glucagon (10(-8) M) caused a drastic decrease in the levels of this effector and a significant fall in lactate production rate. Adrenaline, isoprenaline (a beta-adrenergic agonist) and lactate exerted a similar action decreasing Fru(2,6)P2 concentration. (2) In glucagon pre-treated, glycogen- and Fru(2,6)P2-depleted cells (a situation that mimics the fasted state), Fru(2,6)P2 re-synthesis was strictly dependent on glucose availability. (3) Insulin did not seem to exert a direct action on the control of Fru(2,6)P2 in human hepatocytes. The hormone--which failed to enhance Fru(2,6)P2 in glucose-starved cells--did not further increase Fru(2,6)P2 content nor its time-course evolution as compared to hepatocytes incubated with glucose alone. (4) Lactate caused a significant delay in the glucose-induced increase in Fru(2,6)P2 content that could not be prevented by insulin. (5) Data indicate that in human hepatocytes glucose is a more powerful modulator of Fru(2,6)P2 than insulin, and that variations in blood lactate concentration may also play a role in the control of hepatic Fru(2,6)P2 levels during the fasted-to-fed transition in humans.

Cells, Cultured↗
PubMed1991

[Rhino-sinusal immunology].

Nose and sinus pathology is frequently related to a chronic inflammation, the mechanisms of which involve different cell types that form the MALT, or effector cells. B-lymphocytes are three times more numerous than the T-lymphocytes, where the CD4+ cells predominate over the CD8+ cells. IgA's are mainly secreted by the plasmocytes. In IgA deficiency, a relative increase in IgG or IgD plasmocytes has been recorded. Antigenic information is obtained from cells presenting the antigen. Langerhans-like cells have been described. Two different populations of mast cells have been identified, whilst on the contrary eosinophilic cells are normally absent. The particularities of capillary vascularization and the extent of the nerve fibre network contribute to the creation of a micro-environment interacting with the lymphocytes. The phenomena of cellular interaction are described through the dynamic evolution of the IgE-dependent response in allergic rhinitis.

Humans↗
PubMed1982

Characterization of H-2Db antigens implies haplotype differences in the number of H-2 molecules expressed.

Investigation of the molecular heterogeneity of H-2Db region antigens by using monoclonal antibodies and complex alloantisera has yielded evidence for the existence of only one gene product in this region. Sequential immunoprecipitation and isoelectric focusing analysis suggest that the private H-2.m2 and public H-2.m64 specificities defined by monoclonal or alloantibodies are present on the same molecule. Blocking studies with these reagents indicate these specificities represent two determinants spatially separated on the H-2Db molecule. Functional studies suggest that effector T cells may be generated against both of these determinants or closely associated epitopes, but the majority of the T cells recognize an epitope associated with or identical to the private specificity H-2.m2. Studies of the D region-encoded products of haplotypes besides H-2b have shown two or more distinct molecules can be detected by anti-H-2.m64 in both the H-2d and H-2q haplotypes. The presence of H-2.m64 on a single Db molecule is unique and gives further evidence for the lack of other gene products encoded in this region. Speculations based on the molecular heterogeneity of the D region gene products are made concerning the evolution and genetic organization of H-2 genes.

Animals↗
PubMed1983

The T-cell receptor mediating restrictive recognition of antigen.

Four facts characterize restrictive recognition of antigen. First, in large measure, allele-specific determinants on R are recognized when R is functioning either as a restricting element (RL) or as an allo-target (or even xeno-target) (RF). Second, there is a high frequency of virgin antigen-responsive t cells with alloreactivity, i.e. anti-RF. Third, there is a strict relationship between the class of effector function and the class of RL recognized (restrictive recognition of antigen, XF) but a relaxed relationship between class of effector function and class of RF recognized (alloreactivity). Fourth, the effector T cell functions anti-RL-dependently when XF is the target (restrictive recognition of antigen) and anti-RL-independently when RF is the target (alloreactivity). From these facts are derived the following conclusions. The T cell uses a dual recognitive, single receptor (Model I, Figure 1). A single germ-line VT locus specifying anti-allele-specific recognition of species R encodes both the anti-R and the anti-X combining sites. A "learning" process (occurring in the thymus) is required to establish the restriction specificity (anti-RL) as well as the effector function/class of RL relationship. The repertoire is derived by somatic mutation of all germ-line VT genes specifying anti-RF (Model IA, Table 3 and Figure 9). Given Model IA (Table 3 and Figure 9), we can account further for the existence of an extensive polymorphism of R and minimal polygeneism, for the high frequency of crossreactivity between anti-XF and RF, and for the physiology and genetics of cell-cell communication in immune responsiveness.

Animals↗
PubMed1978

Cytotoxic T-cell responses in mice infected with influenza and vaccinia viruses vary in magnitude with H-2 genotype.

Secondary effector T-cell populations generated by cross-priming with heterologous influenza A viruses operate only in H-2K or H-2D compatible situations, when assayed on SV40-transformed target cells infected with a range of influenza A viruses. The H2-Kb allele is associated with a total failure in the generation of influenza-immune cytotoxic T cells, though this is not seen for the primary response to vaccinia virus. In both influenza and vaccinia development of effector T cells operating at H-2Db is greatly depressed in B10.A(2R) (kkkddb) and B10.A(4R) (kkbbbb), but not in B10 (bbbbbb), mice. However, there is no defect in viral antigen expression at either H-2Kk or H-2Db in B10.A(2R) target cells. This apparently reflects some inadequacy in the stimulator environment, as (A/J X B6) F1 T cells can be induced to respond at H-2Db when exposed to vaccinia virus in an irradiated B6 but not in a B10.A(4R) recipient. The present report, together with the accompanying paper by Zinkernagel and colleagues, records the first rigorous demonstration of both a nonresponder situation and a probable Ir-gene effect for conventional infectious viruses. Possible implications for the evolution of H-2 polymorphism and mechanisms of Ir gene function are discussed.

Animals↗
PubMed1996

Identification of a novel Rac1-interacting protein involved in membrane ruffling.

The Rac GTP binding proteins are implicated in actin cytoskeleton-membrane interaction in mammalian cells. In fibroblast cells, Rac has been shown to mediate growth factor-induced polymerization of actin to form membrane ruffles and lamellipodia. We report here the isolation of a noval Rac1-interacting protein, POR1. POR1 binds directly to Rac1, and the interaction of POR1 with Rac1 is GTP dependent. A mutation in the Rac1 effector binding loop shown to abolish membrane ruffling also abolishes interaction with POR1. Truncated versions of POR1 inhibit the induction of membrane ruffling by an activated mutant of Rac1, V12Rac1, in quiescent rat embryonic fibroblast REF52 cells. Furthermore, POR1 synergizes with an activated mutant of Ras, V12Ras, in the induction of membrane ruffling. These results suggest a potential role for POR1 in Rac1-mediated signaling pathways.

Adaptor Proteins, Signal Transducing↗
PubMed1983

Sequence homology between Lac and Gal repressors and three sugar-binding periplasmic proteins.

Many proteins consist of several independent folding units or domains, each specifying a different function. Repressor proteins such as Lac or lambda cI carry small N-terminal domains which recognize DNA sequences and larger C-terminal domains which are required for effector recognition and/or oligomerization. The native periplasmic metabolite-binding proteins consist of short membrane-recognizing signal sequences and larger C-terminal metabolite-binding domains which also recognize membrane-bound proteins involved in transport and chemotaxis. The DNA-recognizing domains of many repressors are homologous, as are the sugar-recognizing periplasmic proteins. Here I demonstrate that the sugar-binding domains of the Lac and Gal repressors are homologous with the sugar-binding domains of three periplasmic proteins.

Amino Acid Sequence↗
PubMed1989

Stathmin is a major phosphoprotein and cyclic AMP-dependent protein kinase substrate in mouse brain neurons but not in astrocytes in culture: regulation during ontogenesis.

Stathmin is a ubiquitous soluble protein (Mr approximately 19,000; pI approximately 6.2-5.5) whose phosphorylation is associated with the intracellular mechanisms involved in the regulations of cell differentiation and functions by extracellular effectors. It is present in various tissues and cell types and has several nonphosphorylated and increasingly phosphorylated forms, and it is particularly abundant in brain. Very high concentrations of stathmin were also detected in mouse embryo striatal neurons grown in primary culture, whereas stathmin was barely detectable in astrocytes from the same source. Stathmin appeared in neurons as a major substrate for protein phosphorylation and, in particular, for the cyclic AMP (cAMP)-dependent protein kinase, because its phosphorylation was stimulated by cAMP in cell-free preparations and in intact cells by forskolin, a potent activator of adenylate cyclase. During brain ontogenesis, stathmin was first detected at embryonic day 12; its concentration increased until birth and then decreased from postnatal day 10 to adulthood. In parallel, its molecular forms shifted from the least phosphorylated to the more phosphorylated ones. This result may reflect the evolution of the activity of stathmin during development and the subsequent maturation of the brain. In conclusion, our results substantiate the likely role of stathmin as an intracellular relay of extracellular regulations, as they point out its specific importance related to neuronal functions and brain differentiation.

1-Methyl-3-isobutylxanthine↗
PubMed1990

Quantum mechanics and cellular information processing: the self-assembly paradigm.

Biological cells have greater information processing efficiency than the programmable computers used to model them. In part this is due to the larger number of interactions that can contribute to function. General arguments suggest that systems in which quantum features play a prominent role are more powerful than classical physical-dynamical analogs. A hypothetical model, involving macromolecular self-assembly, is used to illustrate how the parallelism inherent in the quantum mechanical wave function could play a role in cellular pattern processing. Signals impinging on the external membrane of the cell trigger the release of specifically shaped macromolecules. These aggregate into a mosaic shape features that reflect different groupings of the signal input patterns. The shape features are in turn read out and connected to effector actions by adaptor molecules. The self-assembly model fits into a more general hierarchical scheme of biological information processing in which macroscopic signals are transduced to mesoscopic and then microphysical representations, processed largely at the microphysical level, and then amplified for macroscopic action. The physical dynamics are controlled by proteins and other macromolecules that are molded through the evolutionary process of variation and selection. The organizational requirements for evolutionary moldability and for efficient information processing function are completely consistent. They include high dimensionality, multiplicity of weak interactions, and hierarchical-compartmental structure.

Biological Evolution↗
PubMed2026

Integrative single-cell and genomic analysis reveals NMB as a driver of metastatic adaptation in esophageal squamous cell carcinoma via metabolic rewiring and immune evasion.

BACKGROUND: Esophageal squamous cell carcinoma (ESCC) has high mortality, and metastasis is the leading cause of patient death. Neuromedin B (NMB) promotes tumor development in various cancers, yet its role in ESCC metastasis remains unclear. METHODS: We integrated single-cell transcriptomic data from matched primary and metastatic ESCC lesions (GSE309392) with bulk transcriptomic cohorts from TCGA and GSE53624. In silico gene perturbation, ligand-receptor communication analysis, and single-cell prognostic model construction were performed, followed by functional validation through siRNA-mediated NMB knockdown in TE-1 and KYSE30 cell lines. RESULTS: NMB was identified as a key gene enriched in metastatic ESCC lesions, and its high expression was associated with coordinated upregulation of oxidative phosphorylation pathway genes and aldo-keto reductase family antioxidant enzymes (AKR1C1, AKR1C2, AKR1B10). Genomic analysis revealed that NMB-high tumors carried a higher clonal mutation burden and a markedly increased frequency of NFE2L2 activating mutations (23% vs. 8%, P = 0.04). In silico knockout and correlation analysis identified AKR1C1 as a downstream effector of NMB. NMB expression was negatively correlated with CD8+ T cell and activated NK cell infiltration. CellChat analysis revealed communication between NMB-positive cells and monocytes via the TGM2-ADGRG1 axis, and specifically detected IFNG signaling. In the single-cell prognostic model, NMB-positive cells accounted for 50% of the high-risk group but only 20% of the low-risk group. TCGA-based survival analysis demonstrated that high NMB expression was associated with shorter overall survival (HR = 2.98, P = 0.03). In vitro NMB-targeted RNA interference markedly inhibited proliferation, colony formation, and migration in TE-1 and KYSE30 cells. CMap screening identified the endothelin-PDE5-cGMP axis as a potential therapeutic target. CONCLUSION: NMB serves as a key driver of metastatic adaptation in ESCC, conferring a survival advantage to tumor cells during metastatic colonization through genomic evolution and immune remodeling, with metabolic adaptation as a downstream consequence of genomic alterations.

NMB↗
PubMed1995

Nitric oxide: an ancestral immunocyte effector molecule.

The presence and the role of nitric oxide synthase (NOS) were investigated in the molluscan hemocytes by immunocytochemical, biochemical and functional approaches. Using an anti-NOS polyclonal antibody, immunoreactivity was observed in the hemocytes, and this reactivity increased after stimulation of the animals with Escherichia coli, indicating that this enzyme is inducible. The NOS inducibility was also histochemically demonstrated by detection of NADPH-diaphorase activity. Biochemical studies show that the enzyme is 70% cytoplasmatic and 30% membrane bound and that the inducible form is mainly cytoplasmatic. The nitrite + nitrate and citrulline formation, the inhibition by N omega-nitro-L-arginine, the Km value for arginine, the calcium and co-enzyme dependence show that the molluscan NOS shares the same properties as the NOS isoenzymes so far studied. However, it cannot be identified with any of these enzymes. It appears to be in some way similar to an inducible form of human hepatocyte NOS. Also cytokines are able to induce NOS. In vitro studies have shown that hemocytes produce nitric oxide (NO), a bactericide substance, and that there is a relationship between the NO system and phagocytosis. The presence of NO in the invertebrate hemocyte demonstrates that critical molecules have been conserved over the course of evolution.

Animals↗