RESUMEN
BACKGROUND: Advanced glycation end-product is a modified form of low-density lipoprotein (AGE-LDL) and accelerates atherosclerosis through undefined mechanisms. Programmed cell death protein 4 (PDCD4), a transcriptional regulator, plays an important role in the regulation of autophagy. The aim of the present study was to investigate the role of PDCD4 involved in AGE-LDL-induced foam cell formation. METHODS: The characterization of AGE-LDL was measured by the thiobarbituric assay and agarose gel electrophoresis in vitro. RAW264.7, THP-1 cell line and primary peritoneal macrophages of mice were transfected with shPDCD4 plasmid AGE-LDL-induced foam cell formation was stained by Oil Red, and the levels of autophagy and apoptosis were determined by Western blot analysis. Autophagosome was observed with immunofluorescence microscopy. Mitochondrial membrane potential and autophagic flux were assessed by flow cytometry. RESULTS: AGE modification resulted in significant reduction of absorbance shown by thiobarbituric assay and augmentation of electrophoresis mobility. Further studies suggest that macrophages exposed AGE-LDL triggered autophagy in the early stage of foam cell formation. PDCD4 deficiency enhanced lipoautophagy but inhibited apoptosis and mitochondria dysfunction. Previous studies have been reported that autophagy is an adaptive response might prevent lesional macrophage apoptosis. In our study, we found PDCD4 deficiency attenuated apoptosis and AGE-LDL-induced foam cell formation relied on increased autophagy. CONCLUSION: Our data revealed that PDCD4 deficiency can facilitate autophagy and benefit for AGE-LDL-induced foam cell formation.
RESUMEN
AIM: To examine the association between dietary macronutrient intake and the risk of age-related cataract (ARC) in middle-aged and elderly men. METHODS: A hospital-based case-control study was conducted from December 2009 to November 2011. Cases (n=360) were patients with cataract aged 45-85 years old, and controls (n=360) were patients who had been admitted to the same hospital for diseases not related with cataract. All subjects were interviewed using a structured interviewer-administrated questionnaire that included information on socio-demographic characteristics, lifestyle habits and detailed medical history, simultaneously, the dietary intakes of nutrients were collected via a valid semi-quantitative food frequency questionnaire (FFQ). The odds ratios (OR) and corresponding 95% confidence intervals (CI) of three types of ARC were estimated using multiple logistic regression models. RESULTS: After adjusting for multiple potential confounders, total dietary intake of carbohydrate was positively associated with cortical cataract, compared to controls in the lowest quartile, and the OR for cases in the highest quartile of intake was 2.471 (95%CI: 1.348-6.043, P=0.027). Higher dietary intakes of protein were protective for posterior subcapsular cataract (PSC) (OR=0.528, 95%CI: 0.148-0.869, P=0.023). Dietary fat intake was not associated with any type of cataract, however, participants in the highest quartile of polyunsaturated fatty acids intake had 2.7 times the risk of nuclear cataract as did those in the lowest quartile (OR=2.742, 95%CI: 1.790-4.200, P=0.033). CONCLUSION: A high intake of carbohydrate and polyunsaturated fatty acid may increase the odds of cortical and nuclear cataract, respectively, whereas high intake of protein, especially animal protein, may protect against PSC cataract. It is possible that dietary changes of target population may reduce the risk of ARC.
