RESUMO
Evidences have suggested that the phosphoryl transfer network by the enzymatic activities of creatine kinase (CK), adenylate kinase (AK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), shows new perspectives to understand some disturbances in the energy metabolism during bacterial infections. Thus, the aim of this study was to evaluate whether Staphylococcus aureus infection in mice could alter serum and cardiac activities of these enzymes and their association to disease pathophysiology. For that, we measured total leukocytes, lymphocytes and neutrophils (just 48â¯h of infection) that were lower in infected animals after 48 and 72â¯h in infected mice compared with negative control, while total protein and globulin plasma levels were higher after 72â¯h of infection. The serum CK activity was higher in infected animals 48 and 72â¯h post-infection compared to the control group, as well as observed for mitochondrial cardiac CK activity. The serum PK activity was higher in infected animals after 72â¯h of infection compared to the control group, and lower in the cardiac tissue. The cardiac AK activity was lower in infected animals 48â¯h and 72â¯h post-infection compared to the control group, while serum and cardiac LDH activities were higher. Based on these evidences, it is possible to conclude that the stimulation of CK activity exerts a key role as an attempt to maintain the bioenergetic homeostasis by the production of phosphocreatine to avoid a rapid fall on the concentrations of total adenosine triphosphate. In summary, the phosphoryl transfer network can be considered a pathway involved in the improvement on tissue and cellular energy homeostasis of S. aureus-infected mice.
Assuntos
Endocardite/metabolismo , Metabolismo Energético/fisiologia , Mitocôndrias Cardíacas/metabolismo , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus/metabolismo , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/sangue , Adenilato Quinase/metabolismo , Animais , Creatina Quinase/sangue , Creatina Quinase/metabolismo , Creatina Quinase Mitocondrial/metabolismo , Modelos Animais de Doenças , Endocardite/microbiologia , Coração/microbiologia , Coração/fisiologia , Homeostase , Leucócitos , Fígado/microbiologia , Fígado/patologia , Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Fosfocreatina/metabolismo , Piruvato Quinase/sangue , Piruvato Quinase/metabolismo , Baço/microbiologia , Baço/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/enzimologiaRESUMO
Several evidences have suggested the involvement of enzymes belonging to the phosphotransfer network, formed by creatine kinase (CK), pyruvate kinase (PK) and adenylate kinase (AK), as well the oxidative stress on the pathogenesis of infectious diseases associated with the central nervous system (CNS). Thus, the aim of this study was to evaluate whether listeriosis alters the brain energy metabolism and/or causes oxidative stress in different brain structures of cattle experimentally infected by Listeria monocytogenes. The cytosolic CK activity was inhibited in the cerebral cortex, cerebellum, brainstem and hippocampus of infected animals compared to uninfected animals, while the mitochondrial CK activity was increased. The PK activity was inhibited in all brain structures of infected animals, while the AK activity was unchanged. Na+, K+-ATPase activity decreased in the cerebral cortex, cerebellum and hippocampus of animals infected by L. monocytogenes. Regarding the oxidative strees variables, the cerebellum and brainstem of infected animals showed increased thiobarbituric acid reactive substances, while the catalase activity was inhibited. Glutathione S-transferarase was inhibited in the cerebral cortex and brainstem of infected animals, and it was increased in the cerebellum. L. monocytogenes was quantified in the liver (nâ¯=â¯5/5) and cerebral cortex (nâ¯=â¯4/5) of the infected cattle. Based on these evidences, the nucleocytoplasmic communication between CK isoenzymes was insufficient to avoid an impairment of cerebral bioenergetics. Moreover, the inhibition on brain PK activity caused an impairment in the communication between sites of ATP generation and ATP utilization. The lipid peroxidation and alteration on antioxidant status observed in some brain structures were also involved during the disease. In summary, these alterations contribute to disease pathogenesis linked to CNS during cattle listeriosis.
Assuntos
Adenilato Quinase/metabolismo , Encéfalo/enzimologia , Doenças dos Bovinos/enzimologia , Creatina Quinase/metabolismo , Listeria monocytogenes/fisiologia , Listeriose/veterinária , Piruvato Quinase/metabolismo , Adenilato Quinase/genética , Animais , Antioxidantes/metabolismo , Encéfalo/metabolismo , Encéfalo/microbiologia , Bovinos , Doenças dos Bovinos/metabolismo , Doenças dos Bovinos/microbiologia , Creatina Quinase/genética , Creatina Quinase Mitocondrial/genética , Creatina Quinase Mitocondrial/metabolismo , Metabolismo Energético , Listeriose/enzimologia , Listeriose/metabolismo , Listeriose/microbiologia , Oxidantes/metabolismo , Estresse Oxidativo , Fosforilação , Piruvato Quinase/genéticaRESUMO
It is becoming evident that bacterial infectious diseases affect brain energy metabolism, where alterations of enzymatic complexes of the mitochondrial respiratory chain and creatine kinase (CK) lead to an impairment of cerebral bioenergetics which contribute to disease pathogenesis in the central nervous system (CNS). Based on this evidence, the aim of this study was to evaluate whether alterations in the activity of complex IV of the respiratory chain and CK contribute to impairment of cerebral bioenergetics during Streptococcus agalactiae infection in silver catfish (Rhamdia quelen). The activity of complex IV of the respiratory chain in brain increased, while the CK activity decreased in infected animals compared to uninfected animals. Brain histopathology revealed inflammatory demyelination, gliosis of the brain and intercellular edema in infected animals. Based on this evidence, S. agalactiae infection causes an impairment in cerebral bioenergetics through the augmentation of complex IV activity, which may be considered an adaptive response to maintain proper functioning of the electron respiratory chain, as well as to ensure ongoing electron flow through the electron transport chain. Moreover, inhibition of cerebral CK activity contributes to lower availability of ATP, contributing to impairment of cerebral energy homeostasis. In summary, these alterations contribute to disease pathogenesis linked to the CNS.
Assuntos
Encéfalo/metabolismo , Creatina Quinase Mitocondrial/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Transporte de Elétrons/fisiologia , Metabolismo Energético , Infecções Estreptocócicas/metabolismo , Streptococcus agalactiae/patogenicidade , Trifosfato de Adenosina/metabolismo , Animais , Encéfalo/microbiologia , Encéfalo/patologia , Brasil , Peixes-Gato/microbiologia , Sistema Nervoso Central/metabolismo , Sistema Nervoso Central/microbiologia , Sistema Nervoso Central/patologia , Creatina Quinase/metabolismo , Doenças Desmielinizantes , Modelos Animais de Doenças , Doenças dos Peixes/enzimologia , Doenças dos Peixes/microbiologia , Doenças dos Peixes/patologia , Gliose/patologia , Homeostase , Humanos , Neutrófilos/microbiologia , Neutrófilos/patologia , Infecções Estreptocócicas/microbiologiaRESUMO
Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na+, K+-ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na+, K+-ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis.
Assuntos
Aeromonas caviae/patogenicidade , Peixes-Gato/microbiologia , Creatina Quinase Mitocondrial/metabolismo , Citosol/metabolismo , Metabolismo Energético/fisiologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Rim/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Brasil , Creatina Quinase/metabolismo , Citosol/enzimologia , Modelos Animais de Doenças , Doenças dos Peixes/patologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Homeostase , Rim/microbiologia , Rim/patologia , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Fosfocreatina/metabolismo , Fosforilação , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
BACKGROUND: Chronic Chagas disease cardiomyopathy (CCC) is an inflammatory dilated cardiomyopathy with a worse prognosis than other cardiomyopathies. CCC occurs in 30 % of individuals infected with Trypanosoma cruzi, endemic in Latin America. Heart failure is associated with impaired energy metabolism, which may be correlated to contractile dysfunction. We thus analyzed the myocardial gene and protein expression, as well as activity, of key mitochondrial enzymes related to ATP production, in myocardial samples of end-stage CCC, idiopathic dilated (IDC) and ischemic (IC) cardiomyopathies. METHODOLOGY/PRINCIPAL FINDINGS: Myocardium homogenates from CCC (N=5), IC (N=5) and IDC (N=5) patients, as well as from heart donors (N=5) were analyzed for protein and mRNA expression of mitochondrial creatine kinase (CKMit) and muscular creatine kinase (CKM) and ATP synthase subunits aplha and beta by immunoblotting and by real-time RT-PCR. Total myocardial CK activity was also assessed. Protein levels of CKM and CK activity were reduced in all three cardiomyopathy groups. However, total CK activity, as well as ATP synthase alpha chain protein levels, were significantly lower in CCC samples than IC and IDC samples. CCC myocardium displayed selective reduction of protein levels and activity of enzymes crucial for maintaining cytoplasmic ATP levels. CONCLUSIONS/SIGNIFICANCE: The selective impairment of the CK system may be associated to the loss of inotropic reserve observed in CCC. Reduction of ATP synthase alpha levels is consistent with a decrease in myocardial ATP generation through oxidative phosphorylation. Together, these results suggest that the energetic deficit is more intense in the myocardium of CCC patients than in the other tested dilated cardiomyopathies.
Assuntos
Complexos de ATP Sintetase/metabolismo , Cardiomiopatia Chagásica/fisiopatologia , Creatina Quinase Mitocondrial/metabolismo , Miocárdio/enzimologia , Complexos de ATP Sintetase/genética , Adolescente , Adulto , Creatina Quinase Mitocondrial/genética , Perfilação da Expressão Gênica , Humanos , Immunoblotting , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Adulto JovemRESUMO
Tyrosine accumulates in inborn errors of tyrosine catabolism, especially in tyrosinemia type II, where tyrosine levels are highly elevated in tissues and physiological fluids of affected patients. Tyrosinemia type II is a disorder of autosomal recessive inheritance characterized by neurological symptoms similar to those observed in patients with creatine deficiency syndromes. Considering that the mechanisms of brain damage in these disorders are poorly known, in the present study our main objective was to investigate the in vivo and in vitro effects of different concentrations and preincubation times of tyrosine on cytosolic and mitochondrial creatine kinase activities of the cerebral cortex from 14-day-old Wistar rats. The cytosolic CK was reduced by 15% at 1 mM and 32% at 2 mM tyrosine. Similarly, the mitochondrial CK was inhibited by 15% at 1 mM and 22% at 2 mM tyrosine. We observed that the inhibition caused by tyrosine was concentration-dependent and was prevented by reduced glutathione. Results also indicated that mitochondrial, but not cytosolic creatine kinase activity was inhibited by tyrosine in a time-dependent way. Finally, a single injection of L-Tyrosine methyl ester administered i.p. decreased cytosolic (31%) and mitochondrial (18%) creatine kinase activities of brain cortex from rats. Considering that creatine kinase is an enzyme dependent of thiol residues for its function and tyrosine induces oxidative stress, the results suggest that the inhibition caused by tyrosine might occur by oxidation of essential sulfhydryl groups of the enzyme. In case this also occurs in patients with tyrosinemia, it is possible that creatine kinase inhibition may contribute to the neurological dysfunction characteristic of tyrosinemia.