Mechanism of inhibition of mitochondrial respiratory complex I by 6-hydroxydopamine and its prevention by desferrioxamine.

Inhibition of mitochondrial complex I by 6-hydroxydopamine was studied in brain and liver preparations. NADH-quinone reductase activity of this complex from rat brain was inhibited by 6-hydroxydopamine partially uncompetitively with respect to NADH with a value of Ki 0.051 +/- 0.

Platelet MAO activity in subtypes of alcoholics and controls in a homogenous population.

The level of platelet monoamine oxidase (MAO) activity has been found to vary between alcoholics and healthy controls and between subtypes of alcoholics, in different populations. This study measured the MAO activity in a group of 46 abstinent alcohol dependent subjects and 22 healthy non-alcoholic controls, male and female, in an ethnically homogenous Irish population. The healthy control subjects had a mean MAO activity of 0.

Exogenous amino acids stimulate net muscle protein synthesis in the elderly.

We have investigated the response of amino acid transport and protein synthesis in healthy elderly individuals (age 71+/-2 yr) to the stimulatory effect of increased amino acid availability. Muscle protein synthesis and breakdown, and amino acid transport were measured in the postabsorptive state and during the intravenous infusion of an amino acid mixture. Muscle-free amino acid kinetics were calculated by means of a three compartment model using data obtained by femoral arterio-venous catheterization and muscle biopsies from the vastus lateralis during the infusion of stable isotope tracers of amino acids.

Studies on the behaviour of semicarbazide-sensitive amine oxidase in Sprague-Dawley rats treated with the monoamine oxidase inhibitor tranylcypromine.

The possibility that increased levels of the activity of the semicarbazide-sensitive amine oxidase (SSAO) might, to some extent, compensate for the loss of monoamine oxidase (MAO) activity in the atypical form of Norrie Disease, was examined using the rat as a model. Long-term treatment with the MAO inhibitor tranylcypromine (1 mg/kg/day) resulted in sustained inhibition of MAO-A and MAO-B activities in liver and brain. After one week, the SSAO activity in heart had increased by 79% above the control levels.

Studies on the time-dependent activation of microsomal semicarbazide-sensitive amine oxidase.

The semicarbazide-sensitive amine oxidase (SSAO) from bovine lung microsomes was activated in a temperature- and time-dependent process. This behaviour was observed when the enzyme was preincubated at 25 degrees C, 37 degrees C and 50 degrees C but not at 4 degrees C. This activation was only observed when benzylamine was used as substrate but not when methylamine, histamine or 2-phenylethylamine were used.

The oxidation of dopamine and epinine by the two forms of monoamine oxidase from rat liver.

Information on the "in vitro" oxidation of epinine by monoamine oxidase (MAO) compared to dopamine is very poor. The aim of this work was to study the oxidative deamination of epinine and dopamine by rat liver MAO-A and MAO-B. The contributions of MAO-A and B to the metabolism of dopamine (55% and 45%, respectively) and epinine (70% and 30%, respectively) were similar.

Monoamine oxidases and related amine oxidases as phase I enzymes in the metabolism of xenobiotics.

To date most of the interest in oxidative metabolism of xenobiotics has been devoted to the role of the microsomal cytochrome P-450 system and to establish the basis for classifying and naming P450 enzymes. The contribution of amine oxidases to the metabolism of xenobiotics has been largely neglected, with the exception of the contribution of monoamine oxidases (MAOs) to the metabolism of exogenous tyramine and the studies of the "cheese effect" produced as the result of ingestion of large amounts of tyramine-containing foods under particular conditions. A review of the involvement of the mitochondrial MAOs in drug metabolism was published in 1988.

Purification and characterization of membrane-bound semicarbazide-sensitive amine oxidase (SSAO) from bovine lung.

Semicarbazide-sensitive amine oxidase (SSAO) has been purified from bovine lung microsomes in a form which is catalytically active and stable to storage. The enzyme, an integral membrane protein, was solubilized with Triton X-100 and purification was achieved, in the presence of detergent, by chromatography with Cibacron Blue 3GA-agarose, hydroxylapatite, Lens culinaris-agarose, Resource Q-FPLC and gel filtration on Superdex 200 HR-FPLC. This is the first reported procedure for the extensive purification of a membrane-bound SSAO.

Exercise-induced changes in protein metabolism.

Exercise has a profound acute effect on protein metabolism. Whereas reports on whole body responses to exercise have varied results, it is generally agreed leucine oxidation is increased during exercise, thus indicating increased net protein breakdown. Following endurance exercise, whole body protein breakdown is generally reduced from resting levels, while following eccentric exercise, both whole body protein breakdown and leucine oxidation are increased.

Conversion of taurine into N-chlorotaurine (taurine chloramine) and sulphoacetaldehyde in response to oxidative stress.

N-Chlorotaurine (taurine chloramine), formed by treating taurine with hypochlorous acid, was shown to decompose to sulphoacetaldehyde with a first-order rate constant of 9.9+/-0.5 x 10(-4).

[Monoamine oxidase inhibitors and pressor response to dietary amines].

Because gastro-intestinal monoamine oxidase (MAO) effectively prevents dietary pressor amines, typically tyramine, from entering the tissues, a marked hypertensive response (the "cheese reaction") can occur when subjects treated with antidepressant MAO inhibitors ingest foods or beverages rich in such amines. Although tyramine is a substrate for both MAO-A and -B, it is only inhibitors of the former enzyme, which are also the effective antidepressants, that give rise to the cheese reaction. This has be shown to be owing to MAO-A being the major form of MAO in intestine and stomach.

[Oxidative modification of monoamine oxidase].

Oxidative modification of monoamine oxidases (MAO) accompanied by alteration of their substrate specificity and sensitivity to specific inhibitors was discovered by Professor V.Z. Gorkin more than 30 years ago.

The UDP glycosyltransferase gene superfamily: recommended nomenclature update based on evolutionary divergence.

This review represents an update of the nomenclature system for the UDP glucuronosyltransferase gene superfamily, which is based on divergent evolution. Since the previous review in 1991, sequences of many related UDP glycosyltransferases from lower organisms have appeared in the database, which expand our database considerably. At latest count, in animals, yeast, plants and bacteria there are 110 distinct cDNAs/genes whose protein products all contain a characteristic 'signature sequence' and, thus, are regarded as members of the same superfamily.

Chronic electrical stimulation increases MCT1 and lactate uptake in red and white skeletal muscle.

We examined whether chronic stimulation of red and white rat muscles increased the concentrations of the monocarboxylate transporter MCT1. Red and white tibialis anterior (RTA and WTA, respectively) and extensor digitorum longus (EDL) muscles were chronically stimulated via the peroneal nerve for 7 days. Stimulated and contralateral control muscles were examined for MCT1 content, L-lactate uptake, lactate dehydrogenase (LDH) isoforms, and muscle fiber composition.

An abundant supply of amino acids enhances the metabolic effect of exercise on muscle protein.

Six normal untrained men were studied during the intravenous infusion of a balanced amino acid mixture (approximately 0.15 g.kg-1.

Mixed muscle protein synthesis and breakdown after resistance exercise in humans.

Mixed muscle protein fractional synthesis rate (FSR) and fractional breakdown rate (FBR) were examined after an isolated bout of either concentric or eccentric resistance exercise. Subjects were eight untrained volunteers (4 males, 4 females). Mixed muscle protein FSR and FBR were determined using primed constant infusions of [2H5]phenylalanine and 15N-phenylalanine, respectively.

Resistance exercise maintains skeletal muscle protein synthesis during bed rest.

Spaceflight results in a loss of lean body mass and muscular strength. A ground-based model for microgravity, bed rest, results in a loss of lean body mass due to a decrease in muscle protein synthesis (MPS). Resistance training is suggested as a proposed countermeasure for spaceflight-induced atrophy because it is known to increase both MPS and skeletal muscle strength.

Assessment of neurotoxicity and "neuroprotection".

Coronal brain slices allow the study of neurotoxicity and "neuroprotection" under conditions where the differentiation-state and interrelationships of the neurones and glial cells are closer to those occurring in the intact tissue than is the case for co-cultured cell systems. The involvement of glial cells in the excitotoxicity of kainate and the potentiation of this toxicity by inhibition of glutamine synthase can be demonstrated. Longer-term toxicity of kainate may also be compounded by depletion of glutathione levels resulting from inhibition of gamma-glutamylcysteine synthase.

Muscle protein metabolism in female swimmers after a combination of resistance and endurance exercise.

There is little known about the responses of muscle protein metabolism in women to exercise. Furthermore, the effect of adding resistance training to an endurance training regimen on net protein anabolism has not been established in either men or women. The purpose of this study was to quantify the acute effects of combined swimming and resistance training on protein metabolism in female swimmers by the direct measurement of muscle protein synthesis and whole body protein degradation.

Inhibition of bovine lung semicarbazide-sensitive amine oxidase (SSAO) by some hydrazine derivatives.

Microsomal semicarbazide-sensitive amine oxidase (SSAO) from bovine lung was shown to be inhibited by a number of hydrazine derivatives, but the mechanisms of inhibition were found to differ. Hydralazine behaved as an irreversible and partially time-dependent inhibitor with an IC50 value of 1 microM under the conditions used. Phenylhydrazine was found to be a potent irreversible inhibitor of SSAO (IC50 30 nM).

Behavior of a novel monoclonal antibody for investigation of ovarian cancer and with possible involvement in multiple drug resistance.

Monoclonal antibodies (MAbs) were raised to an ovarian cancer cell line, OAW42, derived from a patient with a histology of serous cystadenocarcinoma of the ovary, in an attempt to identify novel antigens with a possible role in cancer medicine. One antibody P1H10, subclass IgG1, with a high titer was isolated and shown to recognize an antigen of 48 kDa. Enzyme-linked immunosorbent assay and immunocytochemical studies showed the presence of the target antigen in a number of carcinoma cell lines, including lung and breast, and in two out of three frozen breast tissue specimens.

Nature of inhibition of mitochondrial respiratory complex I by 6-Hydroxydopamine.

The catecholaminergic neurotoxin 6-hydroxydopamine causes parkinsonian symptoms in animals and it has been proposed that reactive oxygen species and oxidative stress, enhanced by iron, may play a key role in its toxicity. The present results demonstrate that 6-hydroxydopamine reversibly inhibits complex I (NADH dehydrogenase) of brain mitochondrial respiratory chain in isolated mitochondria. 6-Hydroxydopamine itself, rather than its oxidative products, was responsible for the inhibition.

Treatment of chronic unstable angina pectoris: use of a totally implantable programmable device for continuous intrathecal infusion of opiates: case report.

We report the case of a 70-year-old man with a 17-year history of angina pectoris, who had previously suffered two documented myocardial infarctions and undergone multiple diagnostic cardiac catheterizations, two coronary artery bypass operations, and several percutaneous transluminal coronary angioplasty procedures. The patient had experienced unstable angina for the past 3 years refractory to maximal medical therapy and was unsuitable for further attempts at revascularization. After a successful trial of epidural infusion of morphine, a totally implantable programmable continuous-infusion device with an intrathecal catheter was implanted in the patient on August 18, 1993, resulting in maintained pain resolution.