Navegando por Palavras-chave "tonin"
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- ItemSomente MetadadadosCaracterização fisiopatológica do sistema renina-angiotensina durante o status epilepticus induzido pela pilocarpina em camundongos transgênicos que expressam tonina de rato(Universidade Federal de São Paulo (UNIFESP), 2013-12-20) Iha, Higor Alves [UNIFESP]; Mazzacoratti, Maria da Graca Naffah Mazzacoratti [UNIFESP]; Universidade Federal de São Paulo (UNIFESP)Objectives: To evaluate the influence of pilocarpine induced long-term convulsive seizure in transgenic mice with overexpressed plasma and brain Ang II. Methods: Using a 320mg/kg pilocarpine dose to induce SE. Following the injection protocol of CAVALHEIRO (1995). We conducted an investigation of both strains (TGM (rTon) and WT C57Black/6) of the following groups: a) saline group; b) 3 hour in SE group; and c) Tonic-clonic seizure group. The last group was created upon the greater incidence of such crises in rTon when compared with WT. During the SE, we accessed several parameters such as latency for the first seizure, tonic-clonic seizure susceptibility and mortality. In their hippocampi was assessed by western-blot, real-time RT-PCR, respectively, protein and RNAm expression levels of AT1, AT2, B1 and B2 receptors as well as of the ACE ACE2, iNOS and eNOS enzymes. The same was made to AT1 receptor in heart. It was also assessed the enzymatic activity of hippocampal, cardiac and plasmatic ECA. Results: In an assessment of how both strains reacted to the pilocarpine induced SE we found no difference on first seizure latency time, but a significant higher frequency of death during the generalized tonic-clonic seizure in rTon mice, 66% in rTon and 34% in WT. In RAS, KKS and NO analyzed parameters we found in studied mice groups strain comparison that rTon showed: a) Saline group: in mRNA hippocampal expression, greater transcript level for iNOS and lower for B1 receptor, in protein quantifying, greater for hippocampal AT1 receptor and lower for cardiac AT1 receptor, thereafter, on ECA enzymatic activity evaluation, greater in hippocampi and heart a and on ACE activity, in heart on AT1 receptor protein levels and in plasma on ACE activity; b) in Tonic-Clonic group: mRNA levels were reduced transcripts of eNOS and iNOS, protein quantification showed raised in hippocampi raised ECA2 and lowered B1 receptor and in heart raised AT1 receptor, thereafter, in ECA enzymatic activity assessment, increased in hippocampal and in plasmatic forms. c) 3h of SE group: in hippocampi mRNA levels were upkeeped for ECA transcript, raised for ECA2 and eNOS transcript and reduced for iNOS transcript, protein analysis showed greater raised hippocampal and heart AT1 receptor and hippocampal lowered B2 receptor. Thereafter, on ECA enzymatic activity evaluation, showed raised activity on hippocampal and plasmatic forms. Conclusion: Transgenic mice showed in assessed tissues differences on RAS, KKS and iNOS expression. These differences resulted in a differentiated response to pilocarpine induced seizure in RAS, KKS, iNOS and eNOS which culminated in a greater propensity to tonic-clonic seizures and greater frequency of death throughout the SE, but didn´t affected the latency period for the first seizure.
- ItemSomente MetadadadosDistribution of tonin- and kallikrein-like activities in rat brain(Elsevier B.V., 1997-09-19) Lopes, E. S.; Sumitani, M.; Juliano, L.; Beraldo, W. T.; Pesquero, J. L.; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP)Tonin- and kallikrein-like activities were investigated in different regions of the rat brain. the highest values of specific tonin activity, expressed as picomoles of angiotensin II liberated per minute per milligram of protein, were found in the neurohypophysis (359 +/- 190) and in the archicerebellum (200 +/- 68). the highest level of total tonin activity (picomoles of angiotensin IT liberated per minute) was observed in the archicerebellum (902 +/- 308) which retained 97% of total tonin activity of whole cerebellum. Tonin activity was not detected in the cortex of cerebellum and in the choroid plexus. Low to intermediate values of specific (1.09 +/- 0.33 to 5.32 +/- 2.37) and total (1.38 +/- 0.55 to 93.00 +/- 49.30) tonin activity were observed in adenohypophysis, cerebellar nuclei, hypothalamus, thalamus, midbrain, pens, medulla and neurohypophysis. the lowest values of specific (0.11 +/- 0.05) and total (0.69 +/- 0.31) activities were observed in the hippocampus. Kallikrein-like activity was expressed as picomoles of p-nitroaniline liberated per minute per milligram of protein. No activity was detected in the neurohypophysis. for other regions, the values of the specific activity ranged between 72 +/- 18 and 282 +/- 14 except for the choroid plexus which was 5 +/- 2. the total kallikrein activity was also homogeneous ranging from 330 +/- 100 to 1870 +/- 112. for the choroid plexus and adenohypophysis the total kallikrein activity was 2.0 +/- 0.8 and 27 +/- 11, respectively. (C) 1997 Elsevier Science B.V.
- ItemSomente MetadadadosIncreased blood pressure and water intake in transgenic mice expressing rat tonin in the brain(Walter de Gruyter & Co, 2010-04-01) Cardoso, Cibele C.; Alenina, Natalia; Ferreira, Anderson J.; Qadri, Fatimunnisa; Lima, Mercia P.; Gross, Volkmar; Todiras, Mihail; Pesquero, Joao B. [UNIFESP]; Pesquero, Jorge L.; Bader, Michael; Max Delbruck Ctr Mol Med; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP)Tonin is a serine proteinase of the kallikrein family that can produce angiotensin II directly from angiotensinogen. To clarify the importance of this enzyme for central nervous control of the cardiovascular system, we generated transgenic mice. TGM(rTon), that express rat tonin in astrocytes. These mice present high levels of tonin mRNA and activity specifically in the brain. As a consequence. TGM(rTon) develop increased blood pressure and water intake. Lisinopril, an ACE inhibitor, is less hypotensive for transgenic mice than for control animals. the AT(I) receptor antagonist candesartan equally lowers blood pressure in transgenic and in control mice. Plasma angiotensin II, but not angiotensin I, is increased in TGM(rTon) compared to the wild type, suggesting release of the peptide from the brain into the circulation. However. AT(I) receptors are desensitized in this transgenic model, as demonstrated by a blunted pressor response to intravenous application of angiotensin II. in conclusion, tonin in the brain may represent an alternative pathway for angiotensin II generation with effects on the cardiovascular system.
- ItemSomente MetadadadosTonin and kallikrein in the brain of transgenic rat line expressing human tissue kallikrein(Lippincott Williams & Wilkins, 2002-02-01) Lomez, ESL; Araujo, R. C.; Bader, Michael [UNIFESP]; Pesquero, João Bosco [UNIFESP]; Pesquero, J. L.; Universidade Federal de Minas Gerais (UFMG); Universidade Federal de São Paulo (UNIFESP); Max Delbruck Ctr Mol MedA transgenic rat line harboring the human tissue kallikrein gene was investigated for expression and activity of tonin and kallikrein in different regions of the brain. the introduction of the transgene into the rat genome produced a significant augmentation of the expression levels and activity of rat tissue kallikrein. the possibility that human kallikrein does not hydrolyze the rat substrate is probably responsible for the augmented expression of the rat enzyme. On the other hand, although expression of tonin was significantly reduced, tonin activity was not altered in most brain structures, except for cerebellum and neurohypophysis.