RESUMEN
The present study aimed to explore the molecular mechanisms underlying the increase of nicotinamide adenine dinucleotide phosphate:quinine oxidoreductase 1 (NQO1) and γ-glutamylcysteine synthetase (γ-GCS) in brain tissues after intracerebral hemorrhage (ICH). The microglial cells obtained from newborn rats were cultured and then randomly divided into the normal control group (NC group), model control group (MC group), rosiglitazone (RSG) intervention group (RSG group), retinoic-acid intervention group (RSG+RA group), and sulforaphane group (RSG+SF group). The expression levels of NQO1, γ-GCS, and nuclear factor E2-related factor 2 (Nrf2) were measured by real-time polymerase chain reaction (RT-PCR) and Western blotting, respectively. The results showed that the levels of NQO1, γ-GCS and Nrf2 were significantly increased in the MC group and the RSG group as compared with those in the NC group (P<0.01). They were found to be markedly decreased in the RSG+RA group and increased in the RSG+SF group when compared with those in the MC group or the RSG group (P<0.01). The RSG+SF group displayed the highest levels of NQO1, γ-GCS, and Nrf2 among the five groups. In conclusion, a medium dose of RSG increased the anti-oxidative ability of thrombin-activated microglia by increasing the expression of NQO1 and γ-GCS. The molecular mechanisms underlying the increase of NQO1 and γ-GCS in thrombin-activated microglia may be associated with the activation of Nrf2.
Asunto(s)
Hemorragia Cerebral/genética , Glutamato-Cisteína Ligasa/genética , Microglía/citología , NAD(P)H Deshidrogenasa (Quinona)/genética , Factor 2 Relacionado con NF-E2/genética , PPAR gamma/genética , Trombina/farmacología , Animales , Animales Recién Nacidos , Células Cultivadas , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Modelos Animales de Enfermedad , Femenino , Glutamato-Cisteína Ligasa/metabolismo , Isotiocianatos/administración & dosificación , Isotiocianatos/farmacología , Masculino , Microglía/efectos de los fármacos , Microglía/metabolismo , NAD(P)H Deshidrogenasa (Quinona)/metabolismo , Factor 2 Relacionado con NF-E2/metabolismo , PPAR gamma/metabolismo , Cultivo Primario de Células , Ratas , Ratas Sprague-Dawley , Rosiglitazona/administración & dosificación , Rosiglitazona/farmacología , Sulfóxidos , Tretinoina/administración & dosificación , Tretinoina/farmacologíaRESUMEN
The relationship between Mg-protoporphyrin IX (Mg-Proto IX) signals and plant's tolerance to cold stress is investigated. Arabidopsis seedlings grown for 3 weeks were pretreated with 2 mM glutamate (Glu) and 2 mM MgCl2 for 48 h at room temperature to induce Mg-Proto IX accumulation. Then cold stress was performed at 4°C for additional 72 h. Glu + MgCl2 pre-treatments alleviated the subsequent cold stress significantly by rising the leaf temperature through inducing Mg-Proto IX signals. The protective role of Glu + MgCl2 treatment was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling, and cyanide-resistant respiration. And the enhancement of cold-responsive gene expression was greatly compromised in the mutants of Mg-Proto IX synthesis, Mg-Proto IX signaling and ABA signaling, but not in the mutant of cyanide-resistant respiration. Cold stress promoted cyanide-resistant respiration and leaf total respiration exponentially, which could be further induced by the Glu + MgCl2 treatment. Mg-Proto IX signals also activate antioxidant enzymes and increase non-enzymatic antioxidants [glutathione but not ascorbic acid (AsA)] to maintain redox equilibrium during the cold stress.