Palmitic acid suppresses autophagy in neonatal rat cardiomyocytes via the cGAS-STING-IRF3 pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effect of palmitic acid (PA) on autophagy in neonatal rat cardiomyocytes (NRCMs) and explore the underlying mechanism.@*METHODS@#NRCMs were isolated and cultured for 24 h before exposure to 10% BSA and 0.1, 0.3, 0.5, or 0.7 mmol/L PA for 24 h. After the treatments, the expressions of Parkin, PINK1, p62, LC3Ⅱ/ LC3Ⅰ, cGAS, STING and p-IRF3/IRF3 were detected using Western blotting and the cell viability was assessed with CCK8 assay, based on which 0.7 mmol/L was selected as the optimal concentration in subsequent experiments. The effects of cGAS knockdown mediated by cGAS siRNA in the presence of PA on autophagy-related proteins in the NRCMs were determined using Western blotting, and the expressions of P62 and LC3 in the treated cells were examined using immunofluorescence assay.@*RESULTS@#PA at different concentrations significantly lowered the expressions of Parkin, PINK1, LC3 Ⅱ/LC3 Ⅰ and LC3 Ⅱ/LC3 Ⅰ+Ⅱ (P < 0.05), increased the expression of p62 (P < 0.05), and inhibited the viability of NRCMs (P < 0.05). Knockdown of cGAS obviously blocked the autophagy-suppressing effect of PA and improved the viability of NRCMs (P < 0.05).@*CONCLUSION@#PA inhibits autophagy by activating the cGAS-STING-IRF3 pathway to reduce the viability of NRCMs.

Compositional studies and Biological activities of Perovskia abrotanoides Kar. oils

BACKGROUND: Current study has been designed to evaluate the chemical composition of essential and fixed oils from stem and leaves of Perovskia abrotanoides and antioxidant and antimicrobial activities of these oils. RESULTS: GC-MS analysis of essential oil identified 19 compounds with (E)-9-dodecenal being the major component in stem and hexadecanoic acid in leaves. In contrast, GC-MS analysis of fixed oil showed 40 constituents with α-amyrin the major component in stem and α-copaene in leaves. The antioxidant activity showed the highest value of 76.7% in essential oil from leaves in comparison with fixed oil from stem (45.9%) through inhibition of peroxidation in linoleic acid system. The antimicrobial assay tested on different microorganisms (e.g. E. coli, S. aureus, B. cereus, Nitrospira, S. epidermis, A. niger, A. flavus and C. albicans) showed the higher inhibition zone at essential oil from leaves (15.2 mm on B. cereus) as compared to fixed oil from stem (8.34 mm onS. aureus) and leaves (11.2 mm on S. aureus). CONCLUSIONS: The present study revealed the fact that essential oil analyzed from Perovskia abrotanoides stem and leaves could be a promising source of natural products with potential antioxidant and antimicrobial activities, as compared to fixed oil.

Mitochondrial dysfunction and activation of iNOS are responsible for the palmitate-induced decrease in adiponectin synthesis in 3T3L1 adipocytes

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress are considered the key determinants of insulin resistance. Impaired mitochondrial function in obese animals was shown to induce the ER stress response, resulting in reduced adiponectin synthesis in adipocytes. The expression of inducible nitric oxide synthase (iNOS) is increased in adipose tissues in genetic and dietary models of obesity. In this study, we examined whether activation of iNOS is responsible for palmitate-induced mitochondrial dysfunction, ER stress, and decreased adiponectin synthesis in 3T3L1 adipocytes. As expected, palmitate increased the expression levels of iNOS and ER stress response markers, and decreased mitochondrial contents. Treatment with iNOS inhibitor increased adiponectin synthesis and reversed the palmitate-induced ER stress response. However, the iNOS inhibitor did not affect the palmitate-induced decrease in mitochondrial contents. Chemicals that inhibit mitochondrial function increased iNOS expression and the ER stress response, whereas measures that increase mitochondrial biogenesis (rosiglitazone and adenoviral overexpression of nuclear respiratory factor-1) reversed them. Inhibition of mitochondrial biogenesis prevented the rosiglitazone-induced decrease in iNOS expression and increase in adiponectin synthesis. These results suggest that palmitate-induced mitochondrial dysfunction is the primary event that leads to iNOS induction, ER stress, and decreased adiponectin synthesis in cultured adipocytes.

Derivados del aceite de palma con concentraciones diferentes de ácidos palmítico y antioxidantes. Efectos sobre lípidos plásmaticos y agregación plaquetaria / Palm oil derivatives with different concentration of palmitic acid and antioxidants. Effects upon plasmatic lipids and platelet aggregability

Se evaluó en conejos el efecto de dietas enriquecidas con colesterol (0.1 por ciento), diferentes concentraciones de ácido palmítico (16:0) y de vitaminas antioxidantes, sobre lípidos plasmáticos y agregación plaquetaria. Los animales se distribuyeron en tres grupos: I. Conejarina (conej.) + colesterol (col) 0.1 por ciento; II: Conej. + col. 0.1 por ciento + aceite de plasma semipurificado 10 por ciento (16:0=39.8 por ciento; retinol 7.3 ug/dL y alfa-tocoferol 157,6 ug/dL); III: Conej. + col. 0.1 por ciento + aceite crudo de palma 10 por ciento (16:0=45.3, retinol 96.4 mug/dL y alfa-tocoferol 322.8 ug/dL). Se praticaron determinaciones mensuales de lípidos plasmáticos (métodos enzimáticos) y a los 10 meses agregación plaquetaria con ADO, y determinaciones plasmáticas de vitaminas C, retinol, y alfa-tocoferol. El colesterol total y la LDLc aumentaron significativamente en todos los grupos. No encontramos variación significativa entre ellos. La agregación plaquetaria fue menor en animales que recibieron dietas enriquecidas con aceite de palma (grupo II y III) (p+0.002 y 0.001). Las concentraciones plasmáticas de retinol y alfa-tocoferol no variaron significativamente. La vitamina C disminuyó en grupo I con respecto a grupos II y III (p<0.005-0.02). Se concluye que la administración de aceite de palma crudo o semipurificado en consejo hipercolesterolémicos, disminuye la agregación plaquetaria sin modificar significativamente la concentración de lípidos plasmáticos.