RESUMEN
NF-kappaB (NF-kappaB), the transcription factors of HIV-1, play an important role in triggering HIV transcription. The inhibition of NF-kappaB activation and their signaling pathway offers a potential anti-HIV therapy strategy. This review reports the mode of action of NF-kappaB in triggering HIV-1 transcription and the status of the inhibitors.
Asunto(s)
Fármacos Anti-VIH/química , VIH-1/genética , FN-kappa B/antagonistas & inhibidores , Fármacos Anti-VIH/farmacología , Infecciones por VIH/tratamiento farmacológico , VIH-1/efectos de los fármacos , VIH-1/metabolismo , Humanos , Proteínas I-kappa B/antagonistas & inhibidores , Proteínas I-kappa B/química , Proteínas I-kappa B/metabolismo , FN-kappa B/química , FN-kappa B/metabolismo , Transducción de Señal , Factores de Transcripción/antagonistas & inhibidores , Factores de Transcripción/química , Factores de Transcripción/metabolismo , Transcripción GenéticaRESUMEN
The aim of our study was to investigate the effects of a new synthetic compound (E) -1- (E) -1- (2- hydroxy -5- chlorophenyl) -3- (3, 5, 6- three methyl pyrazine -2- based) -2- propylene -1 ketone, Z-11, a tetramethylpyrazine analogue, on cerebral ischemia reperfusion injury and the underlying mechanism. 240-260â¯g adult male Wistar rats were subjected to middle cerebral artery occlusion for 2â¯h, followed by 22â¯h of reperfusion. Z-11 (1.7, 3.4 and 6.8â¯mg/kg, i.p.), Edaravone (3â¯mg/kg, i.p.) and DMSO (1, i.p.) was administered at 2â¯h after the onset of ischemia. The rats' neurological score, infarct volume, and body weight change were tested, and some oxidative stress markers such as superoxide dismutase (SOD) activity, glutathione (GSH) and malondialdehyde (MDA) contents were evaluated after 22â¯h of reperfusion. Results showed that neurologic deficit, infarct volume and body weight change were ameliorated after cerebral ischemia reperfusion, and that Z-11 exhibits an excellent effect at a dosage of 6.8â¯mg/kg. This dose also reduced the content of MDA, and upregulated SOD activity and GSH content. Similarly, 6.8â¯mg/kg Z-11 treatment inhibited the reactive oxygen species content and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activity, with the protein levels of Ras-related C3 botulinum toxin substrate1(Rac-1) and mitogenic oxidase (Nox2) downregulated even further. Moreover, the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and its downstream anti-oxidant protein heme oxygenase-1 (HO-1) were upregulated. This indicates that Z-11 could play a protective role in cerebral ischemia-reperfusion injury, and that the protective effect of Z-11 may be related to improvements in the antioxidant capacity of brain tissue. The mechanisms are associated with enhancing oxidant defence systems via the activation of Nrf2/HO-1 and Rac-1/NADPH oxidase pathways.