Com o objetivo de estudar a espécie bubalina quanto ao desempenho de machos bubalinos do nascimento ao abate em regime de pastejo e as características de carcaça em dois pesos de abate, assim como o metabolismo ruminal de dietas com diferentes níveis de proteína e energia e a produção de gases in vitro, o presente trabalho apresenta-se avaliações feitas em quatro partes. A parte 1 foi realizada com búfalos em crescimento criados à pasto, do nascimento até atingirem dois pesos distintos de abate (517 e 568 kg). Avaliações do desempenho foram realizadas com medição do peso vivo, perímetro torácico, altura de cernelha e comprimento corporal e as avaliações das características da carcaça e carne com determinação do rendimento de carcaça quente e fria, perda no resfriamento, peso da gordura, peso do fígado, temperatura e pH da carcaça, área de olho de lombo, espessura de gordura subcutânea, marmorização, maciez e coloração. A segunda parte avaliou dietas com três níveis de proteína (9%, 12% e 15%) no metabolismo ruminal. Os Itens analisados foram: consumo de nutrientes, pH, amônia e ácidos graxos voláteis no rúmen e degradabilidade in situ. Na parte 3, foram avaliadas dietas com dois níveis de proteína (9 e 15%) e dois de energia (65 e 69% NDT) no metabolismo ruminal. Além dos Itens avaliados na parte 2 foram ainda analisados a digestibilidade com uso de marcador, taxa de passagem de liquido ruminal e volume do rúmen e síntese de proteína microbiana. Na última parte foi realizada avaliação de produção de gases in vitro com estudo da cinética da degradabilidade in vitro no tempo de 72 horas. Animais abatidos com diferentes pesos apresentaram desenvolvimento ponderal diferenciado desde o início do crescimento. Não houve diferença entre os dois grupos de animais nas características de carne e carcaça, mas os búfalos abatidos mais pesados (568 kg) apresentaram maior deposição de gordura interna. Níveis de proteína de 9%, 12% e 15% não influenciaram na degradabilidade in situ dos nutrientes e no pH ruminal. A concentração de amônia e AGV foram maiores com níveis de 15% de proteína na dieta. Os níveis de energia (alta ou baixa) combinados com teores de proteína (alto ou baixo) e as correlações entre os níveis de energia e proteína não promoveram efeitos significativos sobre o pH ruminal concentração de amônia, taxa de passagem de líquido e volume ruminal em búfalos, entretanto, dieta com teor de 15% de proteína bruta, independente dos níveis de energia na dieta apresentaram melhores degradabilidades efetivas dos nutrientes. Os níveis de energia não influenciaram significativamente na concentração amônia ruminal ao contrário dos níveis de proteína em que a maior quantidade de proteína na dieta produziu maior concentração de amônia. Não houve diferença significativa na taxa de passagem e volume ruminal entre as quatro dietas fornecidas aos animais. Dietas com diferentes níveis de energia e proteína não influenciaram na qualidade do inóculo para a produção de gases in vitro. / With the aim of studying the buffalo on the performance of males from birth to slaughter in buffalo grazing and carcass characteristics in two slaughter weights, as well as the metabolism of diets with different levels of protein and energy and the production of gases in vitro, this work presents evaluations conducted in four parts. Part 1 was performed with buffalo raised in pasture from birth until they reach two different slaughter weights (517 and 568 kg). Performance assessments were performed with measurement of body weight, chest girth, height and body length and evaluations of carcass characteristics and meat with determining the hot and cold carcass, the cooling loss, fat weight, liver weight, temperature and pH of the carcass, ribeye area, fat thickness, marbling, tenderness and color. The second part evaluated diets with three protein levels (9%, 12% and 15%) on rumen metabolism. Items discussed were the amount of nutrients, pH, ammonia and volatile fatty acids in the rumen and degradability in situ. In Part 3, were evaluated diets with two protein levels (9 and 15%) and two energy (65 and 69% of TDN) on rumen metabolism. Besides the items evaluated in Part 2, were also analyzed the digestibility, passage rate and ruminal volume and rumen microbial protein synthesis. In the last part was done evaluation of gas production in vitro with study of the kinetics of degradation in 72 hours. Animals slaughtered at different weights showed differential weight performance since the beginning of growth. There were no differences between the two groups of animals on meat and carcass characteristics, but the buffaloes slaughtered heavier (568 kg) had higher deposition of internal fat. Protein levels of 9%, 12% and 15% did not influence the in situ degradability of nutrients and rumen pH. The concentration of ammonia and VFA levels were higher with 15% protein diet. Energy levels (high or low) combined with protein levels (high or low) and the correlations between the levels of energy and protein did not cause significant effects on rumen pH, ammonia concentration, liquid passage rate and ruminal volume in buffalo, however, dietary content of 15% crude protein, independent of the energy levels in the diet showed better effective degradability of nutrients. Energy levels did not significantly modify the rumen ammonia concentration unlike the protein levels where in the higher protein diet resulted in higher ammonia concentration. There was no significant difference in passage rate and ruminal volume between the four diets fed to the animals. Diets with different levels of energy and protein did not influence the quality of inoculum for the gas production in vitro.

<p>Initiation of protein synthesis in <i>E.coli </i>involves several steps, which lead to the formation of the first peptide bond. This process requires three initiation factors: IF1, IF2 and IF3. Using a novel technique of combined light scattering and stopped-flow, we elucidated the importance of IF2•GTP conformation for the recruitment of 50S to 30S pre-initiation complex. Moreover, GTP hydrolysis is essential for IF2 release and later binding of ternary complex. Interestingly, a switch in IF2 affinity to G-nucleotides is induced during 30S pre-initiation complexes formation. </p><p>We found that IF1, previously with unknown functions in vitro, increases the rate of naked 70S dissociation by a factor 80 and acts as a fidelity factor in preventing 70S formation containing elongator tRNA instead of fMet-tRNA^fMet. We showed that RRF/EFG/IF3 split both naked and post-termination complexes while IF1/IF3 split only naked ribosomes. The mechanisms of action of RRF/ EFG, the order of their binding to 70S, as well as, the three different conformation of EF-G on the ribosomes are emphasized. Interestingly, 70S formation rate is dependent on the concentration of IF3 and not linear with 50S subunits concentration. We demonstrated that the rate-limiting step in 70S formation is IF3 dissociation from 30S complexes.</p><p>The interplay between initiation factors in the rate and accuracy of protein synthesis was thoroughly studied. Using fMet-tRNA^fMet (initiator tRNA), Met-tRNA^fMet(non-formylated initiator tRNA) and Phe-tRNA^Phe (elongator tRNA), we showed that the major player in the accuracy is IF2 through recognizing the formyl group on fMet-tRNA^fMet, while IF3 acts by increasing both the on- and off-rate of tRNA from 30S pre-initiation complexes.</p><p>Collectively, these novel results describe a comprehensive model of initiation of protein synthesis. In this model, initiation factors increase the rate of fMet-tRNA^fMet binding to 30S subunits, subsequently; the stabilization of fMet-tRNA^fMet by IF2 increases the rate of IF3 dissociation. Later, IF2 in GTP conformation allows 50S docking to 30S pre-initiation complex free of IF3 followed by GTP hydrolysis allowing IF2 release for ternary complex to bind and start elongation of protein synthesis. </p>

<p>Macrolides are a large group of clinically relevant antibiotics that inhibit protein synthesis by binding to the large ribosomal subunit in the peptide exit tunnel, close to the peptidyl transferase center (PTC). We have shown that the peptide length of the resulting peptidyl-tRNA drop-off products is proportional to the distance between the PTC and the respective macrolide in the tunnel. This indicates that macrolides act by sterically blocking the nascent peptide exit path.</p><p>A substantial amount of read-through into full-length product was observed for some macrolides and depends on the relation between the dissociation rate constants for peptidyl-tRNA and the macrolide, respectively. The dissociation rate constant for josamycin is 60 times lower than the dissociation rate constant for erythromycin, which explains why no read-through is seen for josamycin in contrast to erythromycin.</p><p>Macrolides do not compete with binding of ternary complexes, hence they are non-competitive inhibitors. However, the text-book description is not valid for macrolide antibiotics, and we show that this is due to the equilibrium assumption generally used to describe non-competitive inhibitors. Our results suggest that a more thorough mechanistic investigation is required to classify inhibitors than what has been proposed previously.</p><p>Further, we have examined the phenomenon of peptide mediated resistance to macrolides. Our results show that expression of a resistance peptide increases the dissociation rate constant for erythromycin.</p><p>In addition, we have examined the accuracy of protein synthesis on three different levels: (<i>i</i>) How do the three initiation factors accomplish fast and accurate initiation of protein synthesis, (<i>ii</i>) how does proof-reading work on the isoleucyl-tRNA synthetase, and (<i>iii</i>) what is the accuracy in the tRNA selection and how is it accomplished? Our data propose a change of the view on all these mechanisms.</p><p>In conclusion this thesis presents new results on protein synthesis, macrolide antibiotics and macrolide resistance.</p>

Apoptosis plays a crucial role in multicellular organisms by preserving tissue homeostasis and removing harmful cells. The anti-apoptotic B-cell CLL/lymphoma 2 (Bcl-2) and the pro-apoptotic Bcl-2-associated X protein (Bax) act as major regulators of the mitochondrial apoptotic pathway. Activation of Bax via stress signals causes its translocation to the mitochondrial outer membrane (MOM). There, Bax forms homo-oligomeric pores, leading to the release of apoptogenic factors, caspase activation and ultimately cell death. However, the underlying mechanism for the recruitment and pore forming activity of Bax is still not elucidated. Nevertheless, the mitochondrial membrane system seems to play an active and crucial role, presumably being directly involved in the onset of the mitochondrial apoptosis. Since the formation of reactive oxygen species (ROS) is a common stress signal and one of the hallmarks of the mitochondrial apoptosis, direct damage can occur to these membranes by the generation of oxidized phospholipids (OxPls), whose presence can crucially influence the pro-apoptotic action of Bax there. To better understand the impact of OxPls on membranes as well as their potential role in the mitochondrial apoptotic process, defined OxPl species were incorporated into phospholipid vesicles and studied with various biophysical techniques. Differential scanning calorimetry (DSC) and solid state nuclear magnetic resonance (NMR) spectroscopy were used to gain insight into changes in membrane properties in the presence of OxPls. In addition to circular dichroism (CD) spectroscopy, DSC and solid state NMR were furthermore performed to elucidate the impact of OxPls on Bax-membrane interactions. The occurrence of OxPls gave rise to dramatic changes in membrane organization and dynamics, manifested as lateral phase separation into OxPl-rich and -poor domains and modified hydration at the membrane interface. The presence of OxPls also had a great impact on the interaction between Bax and mitochondria-mimicking vesicles, strongly promoting the association of the protein with the membrane. At the MOM, Bax is believed to be inhibited by Bcl-2. How this inhibition occurs is still a mystery due to the lack of biophysical information on Bcl-2, in particular on the full-length protein variant. Since Bcl-2 is also one of the main culprits in the progression of various forms of cancer, knowledge of the structural and mechanistic properties of the full-length protein is essential for a fundamental understanding of its function at a molecular level. To this end, a method for the production of full-length Bcl-2 was developed. By performing cell-free protein synthesis, preparative amounts of the protein were obtained, which enabled a biophysical characterization of the putative interaction between Bax and Bcl-2 using CD and fluorescence spectroscopy. A protocol for the reconstitution of Bcl-2 into proteoliposomes was also developed, promising for future studies of the full-length protein in its native membrane environment; a prerequisite to fully understand its pro-survival functions as well as providing crucial information for the design of novel anti-cancer drugs.

Initiation of protein synthesis in E.coli involves several steps, which lead to the formation of the first peptide bond. This process requires three initiation factors: IF1, IF2 and IF3. Using a novel technique of combined light scattering and stopped-flow, we elucidated the importance of IF2•GTP conformation for the recruitment of 50S to 30S pre-initiation complex. Moreover, GTP hydrolysis is essential for IF2 release and later binding of ternary complex. Interestingly, a switch in IF2 affinity to G-nucleotides is induced during 30S pre-initiation complexes formation. We found that IF1, previously with unknown functions in vitro, increases the rate of naked 70S dissociation by a factor 80 and acts as a fidelity factor in preventing 70S formation containing elongator tRNA instead of fMet-tRNAfMet. We showed that RRF/EFG/IF3 split both naked and post-termination complexes while IF1/IF3 split only naked ribosomes. The mechanisms of action of RRF/ EFG, the order of their binding to 70S, as well as, the three different conformation of EF-G on the ribosomes are emphasized. Interestingly, 70S formation rate is dependent on the concentration of IF3 and not linear with 50S subunits concentration. We demonstrated that the rate-limiting step in 70S formation is IF3 dissociation from 30S complexes. The interplay between initiation factors in the rate and accuracy of protein synthesis was thoroughly studied. Using fMet-tRNAfMet (initiator tRNA), Met-tRNAfMet (non-formylated initiator tRNA) and Phe-tRNAPhe (elongator tRNA), we showed that the major player in the accuracy is IF2 through recognizing the formyl group on fMet-tRNAfMet, while IF3 acts by increasing both the on- and off-rate of tRNA from 30S pre-initiation complexes. Collectively, these novel results describe a comprehensive model of initiation of protein synthesis. In this model, initiation factors increase the rate of fMet-tRNAfMet binding to 30S subunits, subsequently; the stabilization of fMet-tRNAfMet by IF2 increases the rate of IF3 dissociation. Later, IF2 in GTP conformation allows 50S docking to 30S pre-initiation complex free of IF3 followed by GTP hydrolysis allowing IF2 release for ternary complex to bind and start elongation of protein synthesis.

Macrolides are a large group of clinically relevant antibiotics that inhibit protein synthesis by binding to the large ribosomal subunit in the peptide exit tunnel, close to the peptidyl transferase center (PTC). We have shown that the peptide length of the resulting peptidyl-tRNA drop-off products is proportional to the distance between the PTC and the respective macrolide in the tunnel. This indicates that macrolides act by sterically blocking the nascent peptide exit path. A substantial amount of read-through into full-length product was observed for some macrolides and depends on the relation between the dissociation rate constants for peptidyl-tRNA and the macrolide, respectively. The dissociation rate constant for josamycin is 60 times lower than the dissociation rate constant for erythromycin, which explains why no read-through is seen for josamycin in contrast to erythromycin. Macrolides do not compete with binding of ternary complexes, hence they are non-competitive inhibitors. However, the text-book description is not valid for macrolide antibiotics, and we show that this is due to the equilibrium assumption generally used to describe non-competitive inhibitors. Our results suggest that a more thorough mechanistic investigation is required to classify inhibitors than what has been proposed previously. Further, we have examined the phenomenon of peptide mediated resistance to macrolides. Our results show that expression of a resistance peptide increases the dissociation rate constant for erythromycin. In addition, we have examined the accuracy of protein synthesis on three different levels: (i) How do the three initiation factors accomplish fast and accurate initiation of protein synthesis, (ii) how does proof-reading work on the isoleucyl-tRNA synthetase, and (iii) what is the accuracy in the tRNA selection and how is it accomplished? Our data propose a change of the view on all these mechanisms. In conclusion this thesis presents new results on protein synthesis, macrolide antibiotics and macrolide resistance.

Background: Ischemic stroke ranks as the third major cause of clinical mortality and the leading cause of handicap in adults. Each year, stroke occurs in about 30,000 Swedes. The severity of an acute ischemic stroke depends mainly on the degree and duration of local cerebral blood flow (lCBF) reduction. Prompt reperfusion improves neurological deficits, spontaneous electrical activity, energy metabolism, cerebral protein synthesis (CPS), and tissue repair, among which cell proliferation (neurogenesis, gliosis) and revascularization (angiogenesis) may have important functional and therapeutic implications. Aims of the thesis: (1) To establish the photothrombotic ring stroke(PRS) model with late spontaneous reperfusion in adult mice; (2) To explore angiogenesis and neurogenesis in adult brain after focal cerebral ischemia. Materials and Methods: The PRS model in C57 BL adult mice and the middle cerebral artery suture occlusion (MCAO) model in adult Wistar rats were used. The 5-bromodeoxyuridine (BrdU) was delivered into animal after stroke induction to label DNA duplication. CBF, CPS and adenosine triphosphate (ATP) were measured by laser-Doppler flowmetry (LDF), [14C]–Iodoantipyrine and [3H]-Leucine double tracer autoradiography, and bioluminescence, respectively. Immunocytochemistry / immunofluoresence were performed to detect different proteins. The cell marker colocalization was analyzed by three-dimension (3-D) confocal. The cell counting was performed with a stereological counting system. Results: The PRS model was established in adult mice by irradiating the exposed skull with a 514.5 nm argon laser ring beam (3 mm diameter, 0.21 mm thick) at an intensity of 0.65 W/cm2 for 60s, with concurrent erythrosin B (4.25 mg/kg) intravenous infusion for 15s. The central cortical region within the ring locus was progressively encroached by an annular ring-shaped perfusion deficit, where lCBF LDF declined promptly to 43% of the baseline value at 30 min post irradiation. The lCBF-IAP amounted to 46-17-58 ml/100g/min, where CPS varied from 57-38-112% at 4h-48h-7days post ischemia. ATP declined at 4h, achieved its maximum level at 48h and was markedly reduced at 7 days postischemia. Morphologically, at 4h some neurons in the region at-risk appeared swollen, at 48h the majority were severely swollen, eosinophilic and pyknotic. Tissue morphology became partly restored at 7 days post stroke, when numerous cortical cells were immunolabeled by BrdU or the mitosis-specific marker phosphorylated histone H3 (Phos-H3). Some of these cells were even doubly immunopositive to the neuron-specific marker Neu N and the astrocyte marker GFAP, as analyzed by 3-D confocal. In adult rats exposed to MCAO, widespread BrdU-immunolabeled cells appeared in the cortex, ipsilateral striatum and dentate gyrus of the hippocampus. Some of which were doubleimmunolabeled by the neuron specific markers Map-2, β-tubulin III and Neu N as analyzed by 3-D confocal. As early as 24h postischemia, BrdU-immunopositive endothelial cells were aligned as microvessels, some of which exhibited distinguishable lumens in the ischemic boundary zone, where VEGF-A, B, C proteins and their receptors flt-1, fik-1, flt-4 were overexpressed at 72h after MCAO. Conclusion: PRS model in adult mice elicits a dynamic deterioration and then restoration of local CBF, CPS, ATP and tissue morphology in the spontaneously reperfused cerebral cortex at 7d after stroke, where cortical neurogenesis and gliosis occurred. In adult rats with MCAO, neurogenesis occurred at 30 and 60d in the penumbral cortex and striatum. Angiogenesis occurred as early as 24h, which contributed to the spontaneous reperfusion frequently observed in this setting of acute ischemic stroke.

Antibiotic resistance is a growing problem on a global scale. Increasing numbers of bacteria resistant toward one or multiple antibiotics could return us to the high mortality rates for infectious diseases of the pre-antibiotic era. The need for development of new classes of antibiotics is great as is increased understanding of the mechanisms underlying the development of antibiotic resistance. We have investigated the emergence of resistance to peptide deformylase inhibitors, a new class of antibiotics that target bacterial protein synthesis. The fitness of resistant mutants as well as their propensity to acquire secondary compensatory mutations was assessed in order to gain some insight into the potential clinical risk of resistance development. Most of this work was done in the bacterium Salmonella typhimurium, due to the availability of excellent genetic tools to study these phenomena. In addition, we have studied the bacterium Staphylococcus aureus as peptide deformylase inhibitors have been shown to have the greatest effect on Gram-positive organisms. In the course of this work we also examined the mechanistic aspects of translation initiation. Using a cell-free in vitro translation system we studied the effects of various components on translation initiation. These results have been combined with results obtained from resistant and compensated bacterial strains in vivo to gain new insights into the mechanisms of translation initiation.

Although the long-term therapeutic benefits of exercise are indisputable, contractile activity may induce divergent adaptations in insulin-resistant vs. insulin-sensitive skeletal muscle. The purpose of this study was to elucidate if the anabolic response following resistance exercise (RE) is altered in myocellular sub-fractions in the face of insulin resistance. Lean (Fa/?) and obese (fa/fa) Zucker rats were assigned to sedentary and RE groups and engaged in either cage rest or four lower-body RE sessions over an 8-d period. Despite obese Zucker rats having significantly smaller hindlimb muscles when compared to age-matched lean rats, basal 24-h fractional synthesis rates (FSR) of mixed protein pools were near normal in distally located muscle groups (gastrocnemius, plantaris, and soleus) and even augmented in those located more proximally (P<0.05; quadriceps). Although 2 x 2 ANOVA indicated a significant main effect of phenotype on mixed FSR in gastrocnemius and soleus (P < 0.05), phenotypic differences were partially accounted for by an exercise effect in the lean phenotype. Interestingly, obese rats exhibited a significant suppression of myofibrillar FSR compared to their lean counterparts (P<0.05; gastrocnemius), while synthesis rates of mitochondrial and cytosolic proteins were normal (gastrocnemius and quadriceps), suggesting a mechanism whereby translation of specific mRNA pools encoding for metabolic enzymes may be favored over other transcripts (e.g., contractile proteins) to cope with nutrient excess in the insulin-resistant state. Immunoblotting of the cytosolic fraction in gastrocnemius muscle indicated an augmented phosporylation of eIF4EBP1 (+ 9%) and p70s6k (+85%) in obese vs. lean rats, but a more potent baseline inhibition of polypeptide-chain elongation as evidenced by an increased phospho/total ratio of eEF2 (+78%) in the obese phenotype. Resistance exercise did not improve synthesis rates of myofibrillar, cytosolic, or mitochondrial proteins to the same extent in obese vs. lean rats, suggesting a desensitization to contractile-induced anabolic stimuli in the insulin-resistant state. We conclude that insulin resistance has diverse effects on protein metabolism, which may vary between muscle groups depending on fiber type distribution, location along the proximodistal body axis, and myocellular sub-fraction, and may blunt the anabolic response to voluntary resistance exercise.

Sunkieji metalai yra vieni didžiausių ekologinių nuodų. Kadangi apsinuodijimų sunkiaisiais metalais dažnis tebėra didelis, prevencinės strategijos bei veiksmingo gydymo poreikis išlieka aktualūs. Savo eksperimentais mes siekėme įvertinti apsauginį cinko jonų poveikį baltymų biosintezės sistemai bei svarbiausiems jos komponentams (tRNR ir aminoacil-tRNR-sintetazėms) esant slopinančiam kadmio jonų poveikiui. Eksperimentai atlikti su baltosiomis laboratorinėmis pelėmis. Cinko apsauginio poveikio įvertinimui, baltymų biosintezės intensyvumas pelių kepenyse vertintas po 0,5 LD50 CdCl2 (1,6 mg Cd2+ vienam kg kūno masės) ir/arba 0,3 LD50 ZnSO4 (3,1 mg Zn2+ vienam kg kūno masės) tirpalų sušvirkštimo į laboratorinių pelių pilvo ertmę. Baltymų biosintezės intensyvumas pelių organuose nustatytas praėjus 2, 8 ir 24 val. po metalų sušvirkštimo, pagal radioaktyviai žymėto [14C]-leucino įjungimą į naujai susintetintus peptidus ir baltymus. tRNRLeu ir leucyl-tRNR sintetazių aktyvumas nustatytas vykstant reakcijai su [14C]-leucinu. Gauti rezultatai parodė, jog 2 val. po CdCl2 sušvirkštimo, cinko jonai apsaugojo baltymus sintezuojančią sistemą nuo toksinio kadmio poveikio. Praėjus 8 val. po šių abiejų metalų sušvirkštimo, cinko jonai iš dalies normalizavo baltymų biosintezę, tačiau praėjus 24 val., baltymų biosintezės intensyvumas išliko tokio paties aktyvumo, kaip ir kadmiu paveiktose pelėse. Vadinasi, praėjus ilgesniam laikui (24 val.), cinko jonai neapsaugo kepenų transliacijos... [toliau žr. visą tekstą] / The aim of this study was to evaluate protective effects of zinc ions on the total protein synthesis in mouse liver and key components of liver translation machinery (tRNR ir aminoacil-tRNR synthetases) in the present of toxic cadmium ions effects. Experiments were done on white mice using intraperitoneal injections of 0,5 LD50 CdCl2 solution (1,6 mg Cd2+ per 1 kg of body mass) and/or 0,3 LD50 ZnSO4 (3,1 mg Zn2+ per 1 kg of body mass). Protein synthesis was evaluated by incorporation of 14C-labelled leucine into newly synthesized peptides and proteins after 2, 8 and 24 hours of intoxication. Activities of tRNALeu and leucyl-tRNA synthetase were measured by an aminoacylation reaction using 14C-labelled leucine. The data showed that at the 2nd h after CdCl2 injection, Zn2+ abolished deleterious effect of Cd2+ on the protein synthesis in the liver. Although pronounced activation of the protein synthesis was observed after 8 h of intoxication with either Cd2+ or Zn2+, this effect was lower in the presence of both ions. At the 24th h the protein synthesis was as active as in the liver of Cd-treated mice. Thus, Zn2+ can counteract Cd-induced inhibition of protein synthesis in mice liver only at the early stage of Cd2+ intoxication (at the 2nd h). Zn2+ abolished deleterious effect of Cd2+ on the activity of leucyl-tRNA synthetase within 24 h of mice intoxication with CdCl2. In vitro conditions, Zn2+ increased the acceptor activity of leucyl-tRNA synthetase only in low (1... [to full text]