RESUMEN
HS-1-associated protein X-1 (Hax-1) has been suggested to be expressed in various rodent and human tissues. Accumulating evidence has demonstrated that Hax1 exerts an antiapoptotic effect in neurological diseases. Furthermore, it has also been reported that Hax1 interacts with various apoptosisassociated proteins, including high temperature-regulated A2 (HtrA2) and caspase3. Previous studies have indicated that abnormal expression of Hax1 may be associated with the development of the nervous system and with the pathophysiology of neurological diseases, including traumatic brain injury and cerebral ischemia. The present study reported temporalspatial patterns of Hax1 in rat retina following optic nerve crush (ONC). Using western blotting and doubleimmunofluorescence, significant upregulation of Hax1 was observed in retinal ganglion cells (RGCs) in the retina following ONC. Increased Hax1 expression was demonstrated to be accompanied by upregulation of activecaspase3 and HtrA2 following ONC. In addition, Hax-1 colocalized with active caspase3 and HtrA2 in RGCs following ONC. Terminal deoxynucleotidyl transferasemediated biotinylated-dUTP nickend labeling staining suggested that Hax1 was involved in RGC apoptosis following ONC. Thus, these results suggested that Hax1 may participate in regulating RGC apoptosis via interacting with caspase3 and HtrA2 following ONC.
Asunto(s)
Proteínas Portadoras/metabolismo , Retina/metabolismo , Animales , Apoptosis , Biomarcadores , Proteínas Portadoras/genética , Caspasa 3/metabolismo , Modelos Animales de Enfermedad , Expresión Génica , Péptidos y Proteínas de Señalización Intracelular , Masculino , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Traumatismos del Nervio Óptico , Ratas , Células Ganglionares de la Retina/metabolismo , Factores de Empalme Serina-Arginina/genética , Factores de Empalme Serina-Arginina/metabolismoRESUMEN
BACKGROUND: To evaluate the association between plasma total homocysteine (tHcy) levels, serum folic acid, vitamin B(12) and vitamin B(6) levels, methylenetetrahydrofolate reductase (MTHFR) C677T genotype and risk of primary open-angle glaucoma (POAG). CLINICAL RELEVANCE: There are conflicting reports on the association of Hcy, folic acid, vitamin B(12), vitamin B(6), MTHFR, and risk of POAG. We conducted this meta-analysis to derive a more precise estimation of the association. METHODS: Pertinent articles were identified through a systematic search of the EMBASE and Medline databases. Results were pooled using meta-analytic methods. The main outcome measure included tHcy, folic acid, vitamin B(12) and vitamin B(6) levels, and MTHFR C677T genotype. RESULTS: Twelve studies were eligible for Hcy, 6 studies for folic acid, 6 studies for vitamin B(12), 3 studies for vitamin B(6), and 10 studies for MTHFR. The combined results showed that plasma tHcy levels in POAG were 2.05 µmol/L (95% confidence interval [CI], 0.63-3.47) higher than in controls. There was no difference between serum folic acid, vitamin B(6), and vitamin B(12) levels in POAG and controls. The weighted mean difference with 95% CI were 0.34 µmol/L (-0.37 to 1.05), 2.75 µmol/L (-3.68 to 9.18), and 0.97 µmol/L (-30.45 to 32.40), respectively. The MTHFR 677TT genotype was not associated with the risk of POAG (odds ratio, 1.10; 95% CI, 0.83-1.47). CONCLUSIONS: We found that POAG is associated with elevated plasma tHcy levels, but not serum folic acid, vitamin B(12), vitamin B(6) levels, or MTHFR C677T genotype. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.
