RESUMEN
Spontaneous intracerebral hemorrhage (SICH) is a form of brain parenchymal hemorrhage caused by a variety of non-traumatic reasons, resulting in cerebral artery, veins or capillaries rupture. The etiology of SICH is variable, with hypertensive intracerebral hemorrhage being the most common, accounting for 60% ~ 81% of all cases. Cerebral amyloid angiopathy, drug use related hemorrhage, Moyamoya disease are also important causes of SICH. Previous studies showed that genetic factors play an important role in the pathogenesis of SICH. Here the genetic mechanisms of SICH and classification of its etiology are reviewed.
Asunto(s)
Humanos , Investigación Biomédica , Métodos , Hemorragia Cerebral , Diagnóstico , Genética , Predisposición Genética a la Enfermedad , Genética , Variación Genética , Genotipo , Mutación , Polimorfismo de Nucleótido SimpleRESUMEN
OBJECTIVE@#To investigate the effect of the L10P mutation on the cellular mitochondrial disfunction.@*METHODS@#Spectrophotometer, flow cytometry and electron microscope was utilized to examine cell viability, reactive oxygen species (ROS), mitochondrial transmembrane potential, complex I activity and mitochondrial morphous of the HEK293 monoclone cell lines, in which wild-type and L10P mutant DJ-1 protein are stably expressed.@*RESULTS@#Compared with the cell lines expressing empty vector, we found the ROS levels were elevated, the cell viability, mitochondrial transmembrane potential, complex I activity were reduced in the cells expressing L10P mutant DJ-1 protein (P<0.05). We also found mitochondria in these cells were swelling and some mitochondria were vacuolar degeneration. These phenomena were more obvious when rotenone was used. But in the cells expressing wild-type DJ-1, ROS levels were lower, the cell viability, mitochondrial transmembrane potential, and complex I activity were higher than other cell lines (P<0.05), especially under the induction of rotenone. These results suggested that L10P mutant DJ-1 protein probably lost the ability of anti-oxidative stress and affect the normal function of mitochondria.@*CONCLUSION@#The L10P DJ-1 mutation results in a toxic protein, which lacks the protective function of wild-type protein on mitochondria due to the decrease in the ability of anti-oxidative stress.
Asunto(s)
Humanos , Supervivencia Celular , Células HEK293 , Péptidos y Proteínas de Señalización Intracelular , Genética , Potencial de la Membrana Mitocondrial , Mitocondrias , Patología , Mutación , Proteínas Oncogénicas , Genética , Estrés Oxidativo , Proteína Desglicasa DJ-1 , Especies Reactivas de Oxígeno , Metabolismo , RotenonaRESUMEN
OBJECTIVE@#To investigate whether the mutation of P387L in SLC18A2 gene is a cause for sporadic Parkinson's disease (PD) in Chinese Han population. @*METHODS@#A total of 931 subjects (455 sporadic PD patients and 476 healthy controls) were enrolled in our study. SLC18A2 P387L was genotyped by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) and the results were verified by Sanger sequencing. Furthermore, a case-control study was used to investigate the relationship between the mutation and sporadic PD. @*RESULTS@#There was no mutation in any of the 931 individuals. @*CONCLUSION@#The P387L mutation in SLC18A2 gene is rare in Chinese Han population, and P387L might not be a cause for Chinese sporadic PD. However, the role of this mutation in PD needs to be further verified through replication studies with large number of subjects and different population.