Antigas memórias bélicas sobre Javé em Juízes 5,3-5.9-13.19-22.23 e em Habacuque 3,3-6

A imagem de Javé em Juízes 5 constitui-se nas primeiras impressões que o Israel antigo teve do seu Deus. Ela desenha a saída de Javé de sua antiga morada no Sinai para adentrar na terra da Palestina, a fim de lutar por seu povo contra a opressão cananéia. O período tribal foi o momento formativo desse antigo conceito de Javé no Antigo Testamento. Grupos israelitas reformularam o conceito de Javé promulgado pela tradição do Sinai, afirmando, assim, que Javé não é mais o Deus estático e teofânico, morador de uma montanha, mas é o Deus de Israel . E a migração da divindade de um monte para um campo de batalha não representa meramente a caminhada dessa divindade, mas representa o caminhar dos vários estágios em que Israel conceituou seu Deus. Decisivo nessas novas articulações teológicas foi o campo de batalha, que foi o moto da celebração à Javé ressalvada em Juízes 5. Javé é celebrado por seu agir histórico! A história é a mediadora entre Javé e seu povo. Ela é a via pela qual se pronuncia sobre Javé. Assim, as novas conjunturas históricas requerem novas formulações sobre Deus. A antiga memória bélica de Javé contida em Juízes 5 perpassa a história da religião de Israel, podendo ser observada também em Habacuque 3,3-6. Esse é um texto do século VII a.C. Assim, detectamos uma memória corrente na história da religião de Israel, que começou nos momentos antecedentes à da formação da monarquia (Juízes 5) e ainda pode ser notada em Habacuque, no século VII a.C. Nesse desenrolar da religião de Israel, a memória bélica sobre Javé esteve sujeita a várias mutações. Mas, essencialmente, manteve sua proposta: tornar os sujeitos da opressão promulgada pelos impérios em agentes de transformação social. O conceito bélico de Javé patrocinou as revoltas contra o despotismo social, sendo, portanto, uma forma de resistência dos grupos desprestigiados da sociedade, em Israel e Judá

Inactivation of tyrosine hydroxylase by nitration following exposure to peroxynitrite and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)

The decrement in dopamine levels exceeds the loss of dopaminergic neurons in Parkinson’s disease (PD) patients and experimental models of PD. This discrepancy is poorly understood and may represent an important event in the pathogenesis of PD. Herein, we report that the rate-limiting enzyme in dopamine synthesis, tyrosine hydroxylase (TH), is a selective target for nitration following exposure of PC12 cells to either peroxynitrite or 1-methyl-4-phenylpyridiniun ion (MPP+). Nitration of TH also occurs in mouse striatum after MPTP administration. Nitration of tyrosine residues in TH results in loss of enzymatic activity. In the mouse striatum, tyrosine nitration-mediated loss in TH activity parallels the decline in dopamine levels whereas the levels of TH protein remain unchanged for the first 6 hr post MPTP injection. Striatal TH was not nitrated in mice overexpressing copper/zinc superoxide dismutase after MPTP administration, supporting a critical role for superoxide in TH tyrosine nitration. These results indicate that tyrosine nitration-induced TH inactivation and consequently dopamine synthesis failure, represents an early and thus far unidentified biochemical event in MPTP neurotoxic process. The resemblance of the MPTP model with PD suggests that a similar phenomenon may occur in PD, influencing the severity of parkisonian symptoms.

Bax ablation prevents dopaminergic neurodegeneration in the 1-methyl- 4-phenyl-1,2,3,6-tetrahydropyridine mouse model of Parkinson's disease

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) damages dopaminergic neurons in the substantia nigra pars compacta (SNpc) as seen in Parkinson's disease. Here, we show that the pro-apoptotic protein Bax is highly expressed in the SNpc and that its ablation attenuates SNpc developmental neuronal apoptosis. In adult mice, there is an up-regulation of Bax in the SNpc after MPTP administration and a decrease in Bcl-2. These changes parallel MPTP-induced dopaminergic neurodegeneration. We also show that mutant mice lacking Bax are significantly more resistant to MPTP than their wild-type littermates. This study demonstrates that Bax plays a critical role in the MPTP neurotoxic process and suggests that targeting Bax may provide protective benefit in the treatment of Parkinson's disease.

Role of neuronal nitric oxide in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced dopaminergic neurotoxicity.

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes nigrostriatal dopaminergic pathway damage similar to that observed in Parkinson disease (PD). To study the role of NO radical in MPTP-induced neurotoxicity, we injected MPTP into mice in which nitric oxide synthase (NOS) was inhibited by 7-nitroindazole (7-NI) in a time- and dose-dependent fashion. 7-NI dramatically protected MPTP-injected mice against indices of severe injury to the nigrostriatal dopaminergic pathway, including reduction in striatal dopamine contents, decreases in numbers of nigral tyrosine hydroxylase-positive neurons, and numerous silver-stained degenerating nigral neurons. The resistance of 7-NI-injected mice to MPTP is not due to alterations in striatal pharmacokinetics or content of 1-methyl-4-phenylpyridinium ion (MPP+), the active metabolite of MPTP. To study specifically the role of neuronal NOS (nNOS), MPTP was administered to mutant mice lacking the nNOS gene. Mutant mice are significantly more resistant to MPTP-induced neurotoxicity compared with wild-type littermates. These results indicate that neuronally derived NO mediates, in part, MPTP-induced neurotoxicity. The similarity between the MPTP model and PD raises the possibility that NO may play a significant role in the etiology of PD.