排序方式: 共有31条查询结果,搜索用时 234 毫秒
1.
Seminotti Bianca Roginski Ana Cristina Zanatta Ângela Amaral Alexandre Umpierrez Fernandes Thabata Spannenberger Kaleb Pinto da Silva Lucas Henrique Rodrigues Ribeiro Rafael Teixeira Leipnitz Guilhian Wajner Moacir 《Journal of bioenergetics and biomembranes》2021,53(5):525-539
Journal of Bioenergetics and Biomembranes - S-adenosylmethionine (AdoMet) predominantly accumulates in tissues and biological fluids of patients affected by liver dysmethylating diseases,... 相似文献
2.
3.
Carolina G. Fernandes Guilhian Leipnitz Bianca Seminotti Alexandre U. Amaral Ângela Zanatta Carmen R. Vargas Carlos S. Dutra Filho Moacir Wajner 《Cellular and molecular neurobiology》2010,30(2):317-326
High levels of phenylalanine (Phe) are the biochemical hallmark of phenylketonuria (PKU), a neurometabolic disorder clinically
characterized by severe mental retardation and other brain abnormalities, including cortical atrophy and microcephaly. Considering
that the pathomechanisms leading to brain damage and particularly the marked cognitive impairment in this disease are poorly
understood, in the present study we investigated the in vitro effect of Phe, at similar concentrations as to those found in
brain of PKU patients, on important parameters of oxidative stress in the hippocampus and cerebral cortex of developing rats.
We found that Phe induced in vitro lipid peroxidation (increase of TBA-RS values) and protein oxidative damage (sulfhydryl
oxidation) in both cerebral structures. Furthermore, these effects were probably mediated by reactive oxygen species, since
the lipid oxidative damage was totally prevented by the free radical scavengers α-tocopherol and melatonin, but not by L-NAME,
a potent inhibitor of nitric oxide synthase. Accordingly, Phe did not induce nitric oxide synthesis, but significantly decreased
the levels of reduced glutathione (GSH), the major brain antioxidant defense, in hippocampus and cerebral cortex supernatants.
Phe also reduced the thiol groups of a commercial GSH solution in a cell-free medium. We also found that the major metabolites
of Phe catabolism, phenylpyruvate, phenyllactate and phenylacetate also increased TBA-RS levels in cerebral cortex, but to
a lesser degree. The data indicate that Phe elicits oxidative stress in the hippocampus, a structure mainly involved with
learning/memory, and also in the cerebral cortex, which is severely damaged in PKU patients. It is therefore presumed that
this pathomechanism may be involved at least in part in the severe cognitive deficit and in the characteristic cortical atrophy
associated with dysmyelination and leukodystrophy observed in this disorder. 相似文献
4.
Grings Mateus Wajner Moacir Leipnitz Guilhian 《Cellular and molecular neurobiology》2022,42(3):565-575
Cellular and Molecular Neurobiology - Ethylmalonic encephalopathy (EE) is a severe intoxication disorder caused by mutations in the ETHE1 gene that encodes a mitochondrial sulfur dioxygenase... 相似文献
5.
Bruna M. Schweinberger André F. Rodrigues Elias Turcatel Paula Pierozan Leticia F. Pettenuzzo Mateus Grings Giselli Scaini Mariana M. Parisi Guilhian Leipnitz Emilio L. Streck Florencia M. Barbé-Tuana Angela T. S. Wyse 《Molecular neurobiology》2018,55(2):980-988
In the current study, we verified the effects of maternal hypermethioninemia on the number of neurons, apoptosis, nerve growth factor, and brain-derived neurotrophic factor levels, energy metabolism parameters (succinate dehydrogenase, complex II, and cytochrome c oxidase), expression and immunocontent of Na+,K+-ATPase, edema formation, inflammatory markers (tumor necrosis factor-alpha and interleukin-6), and mitochondrial hydrogen peroxide levels in the encephalon from the offspring. Pregnant Wistar rats were divided into two groups: the first one received saline (control) and the second group received 2.68 μmol methionine/g body weight by subcutaneous injections twice a day during gestation (approximately 21 days). After parturition, pups were killed at the 21st day of life for removal of encephalon. Neuronal staining (anti-NeuN) revealed a reduction in number of neurons, which was associated to decreased nerve growth factor and brain-derived neurotrophic factor levels. Maternal hypermethioninemia also reduced succinate dehydrogenase and complex II activities and increased expression and immunocontent of Na+,K+-ATPase alpha subunits. These results indicate that maternal hypermethioninemia may be a predisposing factor for damage to the brain during the intrauterine life. 相似文献
6.
Fabiany da Costa Gonçalves Mateus Grings Natália Schneider Nunes Fernanda Otesbelgue Pinto Tuane Nerissa Alves Garcez Fernanda Visioli Guilhian Leipnitz Ana Helena Paz 《Biotechnology letters》2017,39(4):613-622
Objective
To investigate the effects of oxidative stress injury in dextran sulfate sodium (DSS)-induced colitis in mice treated with mesenchymal stem cells (MSC).Results
Mice exposed to oral administration of 2% DSS over 7 days presented a high disease activity index and an intense colonic inflammation. Systemic infusion of MSC protected from severe colitis, reducing weight loss and diarrhea while lowering the infiltration of inflammatory cells. Moreover, toxic colitis injury increased oxidative stress. Administration of DSS decreased reduced glutathione (GSH) and superoxide dismutase (SOD) activity, and increased thiobarbituric acid-reactive substances levels in the colon. No alteration was found in catalase (CAT) and glutathione peroxidase (GPx) activity. Otherwise, MSC transplantation was able to prevent the decrease of GSH levels and SOD activity suggestive of an antioxidant property of MSC.Conclusion
The oxidative stress is a pathomechanism underlying the pathophysiology of colitis and MSC play an important role in preventing the impairment of antioxidants defenses in inflamed colon.7.
Solano AF Leipnitz G De Bortoli GM Seminotti B Amaral AU Fernandes CG Latini AS Dutra-Filho CS Wajner M 《Free radical research》2008,42(8):707-715
The present work investigated the in vitro effects of isovaleric acid (IVA) and isovalerylglycine (IVG), which accumulate in isovaleric acidemia (IVAcidemia), on important parameters of oxidative stress in supernatants and mitochondrial preparations from brain of 30-day-old rats. IVG, but not IVA, significantly increased TBA-RS and chemiluminescence values in cortical supernatants. Furthermore, the addition of free radical scavengers fully prevented IVG-induced increase of TBA-RS. IVG also decreased GSH concentrations, whereas IVA did not modify this parameter in brain supernatants. Furthermore, IVG did not alter lipid peroxidation or GSH concentrations in mitochondrial preparations, indicating that the generation of oxidants by IVG was dependent on cytosolic mechanisms. On the other hand, IVA significantly induced carbonyl formation both in supernatants and purified mitochondrial preparations from rat brain, with no effect observed for IVG. Therefore, it is presumed that oxidative damage may be at least in part involved in the pathophysiology of the neuropathology of IVAcidemia. 相似文献
8.
Mezzomo Nathana Jamille Becker Borin Diego Ianiski Francine Dotto Fontana Barbara Diehl de Franceschi Itiane Bolzan Juliane Garcez Renata Grings Mateus Parmeggiani Belisa da Silva Fernandes Liana de Almeida Vaucher Rodrigo Leipnitz Guilhian Duval Wannmacher Clovis Milton Cielo Rech Virginia 《Molecular biology reports》2019,46(6):5897-5908
Molecular Biology Reports - Phenylketonuria (PKU) is a metabolic disorder accumulating phenylalanine (Phe) and its metabolites in plasma and tissues of the patients. Regardless of the mechanisms,... 相似文献
9.
Schuck PF Leipnitz G Ribeiro CA Dalcin KB Assis DR Barschak AG Pulrolnik V Wannmacher CM Wyse AT Wajner M 《Neurochemical research》2002,27(12):1633-1639
Short-chain acyl-CoA dehydrogenase deficiency is an inherited metabolic disorder biochemically characterized by tissue accumulation of ethylmalonic (EMA) and methylsuccinic (MSA) acids and clinically by severe neurological symptoms. In the present study we investigated the in vitro effects of EMA and MSA on the activity of creatine kinase (CK) in homogenates from cerebral cortex, skeletal and cardiac muscle of rats. EMA significantly inhibited CK activity from cerebral cortex, but did not affect this activity in skeletal and cardiac muscle. Furthermore, MSA had no effect on this enzyme in all tested tissues. Glutathione (GSH), ascorbic acid and -tocopherol, and the nitric oxide synthase inhibitor L-NAME, did not affect the enzyme activity per se, but GSH fully prevented the inhibitory effect of EMA when co-incubated with EMA. In contrast, -tocopherol, ascorbic acid and L-NAME did not influence the inhibitory effect of the acid. The data suggest that inhibition of brain CK activity by EMA is possibly mediated by oxidation of essential groups of the enzyme, which are protected by the potent intracellular, endogenous, naturally occurring antioxidant GSH. 相似文献
10.
Inhibition of creatine kinase activity from rat cerebral cortex by D-2-hydroxyglutaric acid in vitro
da Silva CG Bueno AR Schuck PF Leipnitz G Ribeiro CA Rosa RB Dutra Filho CS Wyse AT Wannmacher CM Wajner M 《Neurochemistry international》2004,44(1):45-52
D-2-Hydroxyglutaric acid (DGA) is the biochemical hallmark of patients affected by the neurometabolic disorder known as D-2-hydroxyglutaric aciduria (DHGA). Although this disease is predominantly characterized by severe neurological findings, the underlying mechanisms of brain injury are virtually unknown. In the present study, we investigated the effect of DGA on total, cytosolic, and mitochondrial creatine kinase (CK) activities from cerebral cortex of 30-day-old Wistar rats. Total CK activity (tCK) was measured in whole cell homogenates, whereas cytosolic and mitochondrial activities were measured in the cytosolic and mitochondrial preparations from cerebral cortex. We verified that CK activities were significantly inhibited by DGA (11-34% inhibition) at concentrations as low as 0.25 mM, being the mitochondrial fraction the most affected activity. Kinetic studies revealed that the inhibitory effect of DGA was non-competitive in relation to phosphocreatine. We also observed that this inhibition was fully prevented by pre-incubation of the homogenates with reduced glutathione, suggesting that the inhibitory effect of DGA on tCK activity is possibly mediated by oxidation of essential thiol groups of the enzyme. Considering the importance of CK activity for brain metabolism homeostasis, our results suggest that inhibition of this enzyme by increased levels of DGA may be related to the neurodegeneration of patients affected by DHGA. 相似文献