RESUMEN
<p><b>OBJECTIVE</b>To investigate the protective effects of hydrogen peroxide preconditioning (HPP) on the pheochromocytoma (PC12) cells treated with 1-methyl-4-phenylpyridinium (MPP(+)) and to explore the potential mechanisms.</p><p><b>METHODS</b>The viability and apoptosis of PC12 cells were determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and 4',6'-diamidino-2-phenylindole (DAPI) staining, respectively. The expressions of 14-3-3 protein and phosphorylated p38 mitogen-activated protein kinase (MAPK) were determined by Western blot. Enzyme-linked immunosorbent assay (ELISA) was used to measure the activity of extracellular signal-regulated protein kinase 1/2 (ERK1/2).</p><p><b>RESULTS</b>The cell viability decreased and the number of apoptotic cells increased dramatically in MPP(+) group compared with that in Control group. HPP induced a significant increase in cell viability and a marked decrease in population of apoptotic cells of the MPP(+)-treated PC12 cells, accompanied with up-regulation of 14-3-3 protein and increase of ERK1/2 and p38 MAPK activities. The 14-3-3 protein expression was positively correlated with the phosphorylation of ERK1/2. Furthermore, inhibition of the ERK1/2 with PD98059 abolished the 14-3-3 protein up-regulation in PC12 cells induced by HPP.</p><p><b>CONCLUSION</b>HPP protects PC12 cells against MPP(+) toxicity by up-regulating 14-3-3 protein expression through the ERK1/2 and p38 MAPK signaling pathways.</p>
Asunto(s)
Animales , Ratas , 1-Metil-4-fenilpiridinio , Toxicidad , Proteínas 14-3-3 , Apoptosis , Fisiología , Western Blotting , Supervivencia Celular , Ensayo de Inmunoadsorción Enzimática , Peróxido de Hidrógeno , Farmacología , Proteína Quinasa 1 Activada por Mitógenos , Metabolismo , Proteína Quinasa 3 Activada por Mitógenos , Metabolismo , Neuronas , Metabolismo , Patología , Células PC12 , Fosforilación , Transducción de Señal , Fisiología , Regulación hacia Arriba , Proteínas Quinasas p38 Activadas por Mitógenos , MetabolismoRESUMEN
<p><b>OBJECTIVE</b>To investigate the relationship of four single nucleotide polymorphism (SNP) haplotypes in the angiotensinogen (AGT) gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China.</p><p><b>METHODS</b>Total 300 subjects were allocated into three different groups: Group 1, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four polymorphisms at position -152 (G-A), -20 (A-C), -18 (C-T), and -6 (A-G) in the promoter region of AGT.</p><p><b>RESULTS</b>The frequencies of CT genotype of AGT-18 and T allele in Group 1 (P = 0.003, P = 0.004) and Group 2 (P = 0.002, P = 0.002) were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group (P = 0.016), while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 (P = 0.003) compared with the control group, while H5 haplotype frequency which included -20C and -18T was significantly increased in Group 1 (P = 0.006) versus the control.</p><p><b>CONCLUSION</b>The -20 (A-C) and -18 (C-T) of the AGT may play an important role in pathogenesis of primary hypertension; and -20 (A-C), -18 (C-T), and -6 (A-G) may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Hainan, China.</p>