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PubMed1992

Nonspecific hemolytic effector of activated macrophages as activation marker of allograft rejection.

The aim was to assess a nonspecific hemolytic effector of activated monocytes/macrophages, designated spontaneous plaque-forming cell (SPFC), as an activation marker in allograft rejection. An in vitro study on the immunologic characteristics of SPFC monocytes in man and an in vivo study in Lewis rats as to the monitoring of SPFC generation of allograft infiltrating cells with or without immunosuppression were conducted. Hemolysis of SPFC was mediated by CR3 adhesion molecules, detected by Mo-1 and OKM10 monoclonal antibodies. Hemolysis of SPFC was nonspecific, and nonrosette-forming T cells with autologous erythrocytes (non-ARFC-T) acted as suppressor T cells inhibiting SPFC-hemolysis against autologous erythrocytes. A 6-day course of immunosuppression with a daily dose of cyclosporin A (CyA) 10 mg/kg and of FK506 1 mg/kg suppressed the SPFC generation to the level of syngeneic control. In contrast, peak SPFC generation coincided with rejection, and the degree of SPFC generation reflected the grade of histoincompatibility. The present findings suggested that SPFC-activated monocytes/macrophages may be one of the activation markers in allograft rejection and lead to a new concept of graft rejection and self or nonself discrimination mediated by nonspecific, hemolytic SPFC effectors and suppressor T cells inhibiting autoreactivity.

Animals↗
PubMed1981

The macrophage as a cytotoxic effector cell.

Cells of the macrophage lineage possess three different mechanisms allowing them to act as cytotoxic effector cells: lymphokine-activated macrophages kill extracellularly proliferating target cells, preferentially tumor targets, and intracellularly parasitic microorganism like Salmonella, Toxoplasma, Leishmania, and others. Young macrophages and macrophage precursor cells kill antibody coated nucleated target cells. Finally nonadherent, nonphagocytic macrophage precursor cells, released from the bone marrow to sites of inflammation and to the peripheral blood show strong natural killer activity. For the various macrophage functions different subpopulations seem to be responsible as can be seen from data with antimacrophage monoclonal antibodies recognizing and eliminating functionally active subpopulations. The cells of the macrophage system, with their three cytotoxic effector mechanisms which cooperate and enhance each other, are very likely to play an important role in the cytotoxic defense system of the body.

Animals↗
PubMed1986

Immunologic regulator and effector functions in perimyocarditis, postmyocarditic heart muscle disease and dilated cardiomyopathy.

In acute perimyocarditis we found that OKIAI-positive cells were increased, and in dilated cardiomyopathy OKMI-positive cells were increased. No significant alteration in suppressor T cell activity was observed in our patients with either disease. The characteristic immunofluorescent pattern in carditis and postmyocarditic heart disease is the presence of antimyolemmal antibodies with intact rat and human cardiocytes in titers of 1:40-1:320 as antigens. The antimyolemmal fluorescence can be absorbed with the respective causative virus in Coxsackie B, influenza, mumps and EBV-myocarditis, indicating that the antibodies are a cross-reactive. AMLA-positive sera induce cytolysis of vital rat cardiocytes in vitro, suggesting that the antibodies are of pathogenetic relevance. Cytolytic serum activity could be absorbed out with the respective virus. Immunohistologic specimens obtained from patients with carditis demonstrate the fixation of IgG and IgM antibodies; IgG antibodies also occur in dilated cardiomyopathy and coronary artery disease. In dilated postmyocarditic heart disease both antimyolemmal fluorescence and cytolytic activity are preserved at a lower level when compared to carditis. These antibodies can also fix complement. In the acute phase of carditis circulating immune complexes can be demonstrated. Cellular effector mechanisms against vital cardiocytes were maintained or even slightly enhanced in carditis, postmyocarditic and primary dilated cardiomyopathy. In vitro NK cell activity against K 562, however, was decreased. This is compatible with a sustained target-specific cytotoxicity whereas reduced NK cell activity may indicate impairment of this effector organ.

Antibodies↗
PubMed1983

Tumour-reactive lymphocytes stimulated in mixed lymphocyte and tumour culture. Clonal analysis of effector cells in cytotoxic and proliferative assays.

Lymphocytes from cancer patients were stimulated in mixed culture with autologous tumour (MLTC) or pooled allogeneic lymphocytes (MLC). Both protocols induced increased uptake of 3H-thymidine at 5 days and the appearance of lymphoblasts. Blasts were isolated on discontinuous Percoll gradients and either expanded as bulk cultures or cloned directly under limiting dilution conditions in the presence of conditioned medium containing IL-2. Results with MLTC-blast-CTC have been reported elsewhere. MLC-activated cultures lysed autologous tumour but not autologous lymphoblasts. Lysis of some allogeneic tumours, lymphoblasts from members of the inducing pool, and K562 was also apparent. MLC activated cultures did not undergo restimulation in response to autologous tumour or lymphocytes but were restimulated by leukocytes from pool members. MLTC clones showed autologous tumour-specific cytotoxic activity or cross-reactive proliferative responses with tumours of the same site and histology. The majority of MLC clones cytotoxic for autologous tumour were also specific and did not lyse allogeneic tumour, K562, or lymphoblasts from the inducing pool. Two clones lysed autologous tumour and pool members. None of the clones tested proliferated in response to autologous tumour following MLC activation but some were responsive to pool members and one clone was restimulated by autologous monocytes. No association was found between clone phenotype and function. The implication of these data is that the effector cells with activity against autologous tumour induced in MLC arose largely by transstimulation of in vivo-activated tumour reactive lymphocytes by IL-2 release rather than expansion of NK-like effectors or sharing of antigenic specificities between tumour and allogeneic lymphocytes. Since MLC activation of cancer patients lymphocytes does not induce proliferative responses to autologous tumour it is unlikely to be a useful procedure in preparing cells for immunotherapy protocols.

Antibodies, Monoclonal↗
PubMed1982

Antibody-dependent cellular cytotoxicity-mediated serotherapy against murine neuroblastoma. I. In vitro and in vivo treatment using normal, gamma-irradiated and immune-stimulated rat effector cells.

The in vitro and in vivo activity has been investigated of antisera prepared against a murine (C-1300) neuroblastoma line (MNB) capable of differentiation. An antibody-dependent cellular cytotoxicity (ADCC) reaction was employed using rat spleen cells (RSC). ADCC activity in vitro (using 51Cr-release) was shown, but a maximum of only 50% of the immunologically releasable 51Cr was achieved. Nevertheless, in vivo (syngeneic mouse-tumor flank assay) significant delays were obtained in tumor onset and lethality. Under ideal circumstances, i.e., coating of tumor cells prior to inoculation and high RSC effector cell ratios, a significant number of animals could be cured of substantial tumor burdens (10(6) cells). While close proximity of the site of injection of effector cells was required (ectopic injections of RSC were ineffective), the anti-MNB ADCC was shown to be quite active in vivo without external precoating of the cells with antisera. RCS obtained from BCG-treated rats were more numerous and slightly more effective. RSC obtained from gamma-radiated animals retained normal activity. With appropriate antisera this approach could be useful under selected clinical circumstances.

Adjuvants, Immunologic↗
PubMed1985

Adoptive immunotherapy of a BALB/c lymphoma by syngeneic anti-DBA/2 immune lymphoid cells: characterization of the effector population and evidence for the role of the host's non-T cells.

It has been previously shown that the BALB/c lymphoma YC8 is susceptible to lysis by syngeneic anti-DBA/2 lymphocytes and that YC8-bearing BALB/c mice can be cured by adoptive transfer of such immune effectors. In this study in vivo and in vitro functions of the curative immune lymphocytes have been evaluated together with the role of the host immune system in the mechanism of tumor eradication. It was found that the curative anti-DBA/2 lymphocytes were not directly cytotoxic to YC8 cells although they developed into YC8-lytic cells after in vitro restimulation with YC8. In vivo, the immune lymphocytes were able to mediate a tumor-specific delayed type hypersensitivity reaction against YC8 but had a low tumor-neutralizing activity in the Winn assay. Proliferation of infused BALB/c anti-DBA/2 lymphocytes was necessary for the in vivo therapeutic effect, since irradiation of effector cells or treatment of the donor immune lymphocytes with vinblastine abolished their curative capacity. Immunodepression of the T cell compartment of the prospective tumor-bearing animals by thymectomy plus irradiation or its abrogation in B mice (thymectomized, lethally irradiated, and reconstituted with fetal liver cells) did not interfere with the therapeutic effect of the transferred anti-DBA/2 lymphocytes. Blocking the macrophage functions of the host by carrageenan, however, abolished the therapeutic effect of immune lymphocytes. These data indicate that a radiation-resistant, non-T cell is involved in the tumor eradication induced by anti-DBA/2 lymphocytes. It was also shown that cured mice, tested 90 days after therapy, become resistant to 5 X 10(3) LD80 YC8 cells and that this resistance was due to the presence of memory cells derived from the transferred and not from the host lymphocyte population.

Animals↗
PubMed1987

Studies on the recovery from tolerance to tumor antigens. II. Accelerated recovery of tumor-specific effector T cells in tolerant mice by applying T-T cell interaction mechanism.

C3H/He mice were injected i.v. with heavily X-irradiated syngeneic X5563 tumor cells three times at 4-day intervals. This regimen resulted in the abrogation of the potential to generate X5563 tumor-specific T cell-mediated immunity as induced by i.d. inoculation of viable X5563 tumor cells followed by surgical resection of the tumor, representing the tolerance induction. Although such a tumor-specific tolerant state was long-lasting, the recovery of anti-X5563 effector T cell responses was observed when the above ordinary immunization procedure was performed 6 months after the tolerance induction. The present study investigated whether the recovery from the tolerance can be accelerated by applying a helper-effector T-T cell interaction model in which enhanced anti-X5563 immunity is obtained by priming mice with BCG and by immunizing X5563 tumor cells modified with BCG cross-reactive MDP hapten (designated as L4-MDP) in the presence of anti-L4-MDP helper T cells preinduced with BCG. The results demonstrated that BCG-primed mice which received the tolerance regimen failed to generate anti-X5563 immunity when the ordinary immunization was performed 2 or 3 months after the tolerance induction. In contrast, the immunization of BCG-primed and X5563-tolerant mice with L4-MDP-coupled X5563 tumor cells at comparable timing to that of the ordinary immunization were capable of generating potent X5563-specific in vivo protective T cell-mediated immunity. As control groups, BCG-primed or unprimed tolerant mice did not develop anti-X5563 immunity when immunized with L4-MDP-uncoupled or L4-MDP-coupled tumor cells, respectively. These results indicate that immunization of BCG-primed, tumor-tolerant mice with L4-MDP-modified tumor cells results in accelerated recovery from the tumor tolerance.

Animals↗
PubMed1996

Interactions of 8-anilino-1-naphthalenesulfonic acid (ANS) and cytochrome P450 2B1: role of ANS as an effector as well as a reporter group.

Interactions of cytochrome P450 2B1 were probed using 8-anilino-1-naphthalenesulfonic acid (ANS), a well known and frequently used reporter group for hydrophobic interactions. Titration of cytochrome P450 2B1 with ANS revealed 6.6 +/- 0.2 ANS binding sites per molecule of P450 2B1 with a Kd value of 42 +/- 2 microM. In our evaluation of the consequences of the binding of ANS to cytochrome P450 2B1, we found that the binding of ANS to P450 2B1 increased benzphetamine demethylation activity by 1.5-fold, indicating a role for ANS as an effector in addition to its role as a reporter group. Kinetic analysis of the effects of ANS on P450 2B1-dependent demethylation activity revealed that ANS increased both the Vmax and K(m) of the benzphetamine demethylation reaction. ANS stimulation of activity appears not to be due to the replacement or augmentation of the role of lipid since studies of binding and catalytic activities in the presence and absence of added lipid gave the same array of effects. These results demonstrate that ANS can bind to cytochrome P450 2B1 as would be expected of a reporter group probe but show in addition that this probe also acts as an effector molecule stimulating catalytic activity. Thus, results of ANS studies should be viewed with caution since the molecule may play more than one role in its reaction with a protein.

Anilino Naphthalenesulfonates↗
PubMed1988

Distinct affinity and effector residues in the binding site for a regulatory ligand. The mitochondrial uncoupling protein as a model.

A hypothesis concerning two distinct classes of amino acid residues in some regulatory binding sites is proposed. The "affinity residues" are those that are unable to transduce the ligand information signal but are responsible for overcoming the barrier for the attachment of a ligand to its binding site while the "effector residues" transfer the binding signal to the other functional part of the protein, which then undergoes a non-equilibrium energetic cycle induced by interaction with the ligand. As an example, the purine nucleotide inhibition of H+ transport through the uncoupling protein of brown adipose tissue mitochondria is discussed; there is a concentration range in which the nucleotide is bound but does not inhibit H+ transport. This is interpreted in terms of inaccessibility of the effector residues inducing H+ transport inhibition below a certain threshold concentration.

Adenosine Triphosphate↗
PubMed1981

Positive regulation in a eukaryote, a study of the uaY gene of Aspergillus nidulans. II. Identification of the effector binding protein.

In this publication we report the identification of a protein likely to be coded by uaY, a regulatory gene in the ascomycete Aspergillus nidulans. uaY is a positive control gene necessary for the expression of at least eight unlinked structural genes involved in purine uptake and degradation (Scazzocchio and Gorton 1977). The physiological effector of the uaY system is uric acid, while some of its thioanalogs serve as gratuitous inducers. Effector binding proteins were detected by binding to 2-thiouric acid after phosphocellulose column chromatography, or as uric acid binding fractions after DNA-cellulose column chromatography. Two binding peaks are present in mycelial extracts purified by either method. These are missing in a putative small deletion of the uaY gene. A "leaky" mutation, uaY109 described in detail elsewhere (Scazzocchio et al. 1980) shows only one peak. The wild type peaks eluted at 55 mM NaC1 and at 720 mM NaCl while the peak present in uaY109 is eluted at 120 mM NaC1. This implies that at least one peak represents a protein coded by the uaY gene. The major peak was analysed by equilibrium dialysis experiments. These establish a Kdiss approximately 2 X 10(-7) and a minimum number of binding sites of 3 X 10(-14) moles/mg of soluble protein in a crude extract derived from protoplast lysis. An extract from a strain carrying the uaY207 deletion, purified blind, lacks any binding activity in the equilibrium dialysis cell.

Aspergillus nidulans↗
PubMed1982

Cell-mediated cytotoxicity against HLA-D-region products expressed in monocytes and B lymphocytes. IV. Characterization of effector cells using monoclonal antibodies against human T-cell subsets.

The cytotoxic effector cells that recognize HLA-D-region determinants and their precursors were characterized using monoclonal antibodies against human T lymphocytes and T-cell subsets. These studies were performed using MLC combinations giving rise to cytotoxic cells specific for both class I (HLA-A, B, C) and class II (HLA-D-region) antigens, and then tested against target cells displaying relevant antigens of only one class. Both class I and class II specific CTL (cytotoxic T lymphocytes) were inhibited by treatment with the OKT3 monoclonal antibody and complement, indicating that the effector cells were T lymphocytes. A major portion of class II specific CTL, and their precursors, were inhibited by OKT4 and complement, while class I specific CTL from the same cultures were not. The T4+T8- cell subset has previously been associated with helper or inducer functions, but not with cytotoxicity. The present findings indicate that class I and class II specific CTL, and their precursors, are different on the basis of the class of target antigen recognized and on the basis of surface phenotype detected by monoclonal antibodies.

Antibodies, Monoclonal↗
PubMed1979

Incorporation of inositol hexaphosphate into intact red blood cells. I. Fusion of effector-containing lipid vesicles with erythrocytes.

Fluid charged lipid vesicles loaded with an inositol hexaphosphate solution were used to transport this allosteric effector into human intact red blood cells. Rate and extent of uptake of the vesicles and of the effector by the red blood cells were measured as changes in the O2 half-saturation pressure and the 31P-NMR spectra of the intracellular inositol hexaphosphate-haemoglobin complex.

Erythrocytes↗
PubMed1986

Differential effect of hybrid resistance on the localization of virus-immune effector T cells to spleen and brain.

The hybrid resistance (Hr) effect operates in the lymphocytic choriomeningitis (LCM) in vivo transfer model to inhibit both the level of cytotoxicity T lymphocyte (CTL) generation in spleen and the induction of inflammation in cerebrospinal fluid (CSF). The effect is seen when LCM virus-immune T cells that are homozygous for H-2Db are injected into virus-infected, immunosuppressed recipients that are heterozygous for this allele, or into radiation chimeras that express an appropriate F1 phenotype. Evidence that Hr to T-cell transfer is cell-dose-dependent and tends to diminish with age was found in both chimeric and normal F1 mice. Inhibition of the capacity of injected T cells to cause meningitis is a more sensitive measure of Hr than is the further stimulation of CTL effectors in recipient lymphoid tissue. The injection of large numbers of H-2b virus-immune T cells into (H-2k X H-2bF1----H-2k) virus-infected recipients did not induce any cellular extravasation into CSF, though potent H-2b-restricted CTL effectors were generated in recipient spleen. Evidence of minimal inflammatory process was found in one experiment where these chimeras were given a comparable dose of (H-2b X H-2d)F1 immune spleen cells. Development of this T-cell-mediated immunopathological process depends essentially on the expression of the appropriate H-2 restriction element on radiation-resistant host cells which, in this case, presumably constitute part of the physiological barrier between blood and CSF.

Animals↗
PubMed1984

Characterization of human lymphocyte subpopulations: alloreactive cytotoxic T-lymphocyte precursor and effector cells are phenotypically distinct from Leu 2+ suppressor cells.

The OKT8/Leu 2+ human T-cell subset contains cells which perform suppressor and cytotoxic functions. We have recently produced two monoclonal antibodies (termed 2D2 and D12) which define four subpopulations of human E+ cells. Previous studies have shown that the Leu 2+ cells that suppress T-cell proliferative responses have the 2D2+D12+ phenotype. In the present studies, we have used these antibodies and fluorescence-activated cell sorter techniques to characterize the phenotype of cytotoxic T lymphocytes generated in allogeneic mixed lymphocyte cultures. These studies indicate that the cytolytic effector cells which recognize class I major histocompatibility antigens express the 2D2+D12- phenotype. The phenotype of the precursor cells for these cytotoxic T cells was similarly demonstrated to be 2D2+D12-. The subset of E+ cells with NK cytolytic activity expressed the 2D2-D12+ phenotype. These data demonstrate that the Leu 2+ precursor and effector cytotoxic T cells reactive against class I alloantigens are phenotypically distinct from the Leu 2+ cells previously shown to suppress T-cell proliferative responses.

Antibodies, Monoclonal↗
PubMed1991

The 5-HT receptor--G-protein--effector system complex in depression. I. Effect of glucocorticoids.

Hormonal modulation of neurotransmission emerged as a concept from the recognition that adrenocortical steroids exert profound effects at the level of receptors, G-proteins and effector units. G-proteins, a family of guanine nucleotide binding regulatory components that couple neurotransmitter receptors to various types of intracellular effector systems, appear to be a key target of glucocorticoid (GC) action in the CNS. It is thought that Gs/Gi mediates stimulation/inhibition of adenylate cyclase (AC system), which forms cyclic AMP as second messenger, while receptors stimulating phospholipase C do so through Go to produce two second messengers, inositol 1,4,5-triphosphate and diacylglycerol (PI system). Recent evidence suggests that GC increase Gs alpha-and decrease Gi alpha-protein subunit expression without affecting Go alpha. Activation of central pre- and postsynaptic 5-HT1A receptors which are linked to the Gi-AC complex, induces hypothermia and ACTH/cortisol release in rodents and humans. Compared with controls, patients with a major depressive disorder exhibit increased basal cortisol secretion associated with decreased hypothermic and ACTH/cortisol responses. The attenuated neuroendocrine and thermoregulatory response to 5-HT1A receptor activation may reflect a GC-dependent feedback inhibition of the hypothalamic-pituitary-adrenal (HPA) system and subsensitivity of the presynaptic 5-HT1A-Gi-AC complex function. Differential regulation of 5-HT1A and 5-HT2 function leading to a relative 5-HT2-Go-PI complex supersensitivity may maintain HPA hyperactivity during the course of depression. These findings corroborate recent reports that GC, via GC-GC receptor (GR) complex activated promotion of gene transcription, modify the expression 5-HT1A-coupled Gi (but not 5-HT2-coupled Go) resulting in altered sensitivity of 5-HT1A-mediated signal transduction and further support the hypothesis of a differential regulation of 5-HT1A and 5-HT2 receptor function and a GC-GR/5-HT1A-G-protein--effector system-related abnormality in depression.

Adenylyl Cyclases↗
PubMed1978

[Effector function of acute leukemias in "spontaneous" (SCMC) and antibody dependent cellular cytotoxicity-tests (ADCC) (author's transl)].

Blood lymphocytes from 13 untreated acute leukemia patients, 3 pre-leukemias 3 immunoblastic lymphadenopathias and one infectious mononucleosis showed significantly lower spontaneous (SCMC) and antibody-dependent cellular cytotoxicity (ADCC) against 51Cr-labeled allogeneic melanoma cells of the IGR3 cell line than effector lymphocytes from 20 age- and sex matched control persons. While control lymphocytes exhibited the highest cytotoxic activity after depletion of mononuclear phagocytes (Fraction FFF), followed by the "Ficoll" purified Fraction F and defibrinated whole blood, the reverse was true for acute leukemias: here, the highest cytotoxicity was found in whole blood followed by the lymphocyte fractions F and FFF. Comparatively high cytotoxicity was found with two leukemia patients who had received blood transfusions the day before testing. During the course of an acute erythroleukemia chemotherapy drastically reduced SCMC and ADCC activities. A therapeutical splenectomy, on the other hand, did not affect cellular cytotoxicity in the case of a hairy cell leukemia. The angioimmunoblastic lymphadenopathies showed strikingly high percentages of EA- and EAC-rosettes forming cells and showed a marked increase of SCMC and ADCC activities after elimination of mononuclear phagocytes from the effector cell population.

Acute Disease↗
PubMed1995

Influence of cAMP-effector-agonists on the synthesis of metallothionein in rat primary hepatocytes.

The model of rat primary hepatocytes incubated in DMEM/F12 (Ham) medium was used for studying the influence of the cAMP-effectors epinephrine (100 microM), norepinephrine (100 microM), glucagon (1 microM) and isoproterenol (1-1000 microM) as well as the synthetic cAMP-analogon dibutyryl-cAMP on the metabolism of metallothionein. Liver parenchymal cells isolated by a two-step collagenase perfusion were incubated with DMEM/F12 containing 5% (v/v) fetal calf serum (FCS) and 20 microM zinc in Petri dishes. Experiments were initiated after a 24 h equilibration period by adding the agonists for 18 h. MT in hepatocyte homogenates was quantified by the 109Cd-hemoglobin-binding assay. Cell viability was assessed by the activity of the cytosolic enzyme lactate dehydrogenase (LDH) liberated into the culture medium and by trypan blue exclusion. Isoproterenol and glucagon produced a significant increase of cytosolic MT about 50%. In contrast, incubation with epinephrine and norepinephrine did not lead to any significant effects in the amount of hepatic metallothionein. Simulating the influence of cAMP by dibutyryl-cAMP (500 microM) did not affect the content of hepatic metallothionein. To examine transcriptional and translational regulatory effects supplementation of cycloheximide (0.1-500 microM) and actinomycin D (0.1-100 microM) showed a total inhibition of the agonist induced amounts. Particularly in combination with isoproterenol low LDH activities reflected a high viability of hepatocytes. In conclusion, in primary hepatocyte cultures cAMP-mobilizing-agonists like isoproterenol and glucagon indicate an independent effect on the MT-metabolism. This is possibly due to the de novo synthesis of the protein because suppression by actinomycin D can be observed. However, cAMP-effectors do not seem to be involved in the induction of metallothionein because theophylline and dibutyryl-cAMP did not affect MT-metabolism by suppressing the phosphodiesterase or by stimulating the cAMP-cascade.

Analysis of Variance↗
PubMed1975

The steady state activity of succinate dehydrogenase in the presence of opposing effectors. 1. The effect of L malate and CoQH2 on the enzymic activity.

Succinate dehydrogenase is subjected to positive and negative modulation. The negative modulators oxaloacetate and D- or L-malate transform the enzyme into a nonactive complex in which oxaloacetate is bound. The deactivation by malate involves its oxidation by the succinate dehydrogenase which then deactivates the enzyme. In the present study we measured the activity of succinate dehydrogenase in the presence of two opposing effectors,L-malate as deactivator and CoQH2 as an activator. With these opposingeffectors present, the catalytic activity of succinate dehydrogenase assumes a steady state, the level of which is a function of the concentration of the two effectors. At lowconcentration of L-malate all of the succinate dehydrogenase activity is protected by CoQH2, while at saturating malate concentrations only 60-70% of activity is protected. Kinetic analysis of the approach to the steady state indicates that the protective effect of CoQH2 is not due to its activator property but due to its ability ofreduce the enzyme. This was verified by carrying out a radox titration of succinatedehydrogenase activity in the presence of L-malate. A redox active component was characterized with E = +25 mV and n = 1.8. When this component is reduced, L-malate cannot deactivate the succinate dehydrogenase, but when in the oxidized state the enzyme is susceptible to such deactivation. It is proposed that this group participates in the regulation of the activity of succinate dehydrogenase in the mitochondria.

Animals↗