MiR-29a mediates the apoptotic effects of TNF-α on endothelial cells through inhibiting PI3K/AKT/BCL-2 axis.

Endothelial cell apoptosis driven by inflammation (TNF-α) plays a critical role in the pathogenesis of atherosclerosis, but the exact molecular mechanisms are not clearly elucidated. MicroRNA (miR)-29 families (a/b/c) take important roles in pathophysiological processes of atherosclerosis, also the underlying mechanisms have not been fully clarified. The aims are to explore whether or not miR-29 families mediate the apoptotic effects of TNF-α on endothelial cells and uncover the underlying molecular mechanisms. In this study, MTT assay and flow cytometer analysis were employed respectively to determine the proliferation and apoptosis of human umbilical vascular endothelial cells (HUVECs) under TNF-α exposure. Real-time quantitative PCR and western blot were performed to detect the levels of target RNAs and proteins/their phosphorylation in HUVECs. TNF-α could inhibit HUVEC proliferation and induce HUVEC apoptosis in a positive dose- and time-dependent manner, with a similar way of miR-29a upregulation, but no effects on miR-29b/c. Upregulation of miR-29a with its mimics enhanced the apoptotic effect of TNF-α on HUVECs, but downregulation of miR-29a using anti-miR-29a blocked up its apoptotic effect. MiR-29a inhibited the expression of PI3Kp85α and Bcl-2 and blocked up the signal transduction of PI3K/AKT/Bcl-2 axis to mediate the apoptotic effect of TNF-α on HUVECs. Mediating the inflammation-driven endothelial cell apoptosis is an important biology mechanism by which miR-29a promotes atherosclerosis and its complications. MiR-29a will be a potential diagnostic and therapeutic target for atherosclerotic cardiovascular diseases; it is worthwhile to further study.

Investigation into the Relationship between Spermidine Degradation and Phenolic Compounds Biosynthesis in Barley Seedlings under Ultraviolet B Stress.

Barley germination under ultraviolet B (UV-B) illumination stress induces effective accumulation of phenolic compounds in the barley. Spermidine can enhance the biosynthesis of phenolic compounds and alleviate the oxidative damage caused by UV-B. To better understand the function of spermidine, inhibitors of enzymes that are involved in the degradation of spermidine and the synthesis of gamma-aminobutyric acid (GABA), the product of spermidine degradation, were applied to barley germinated under UV-B treatment. The results showed a more severe oxidative damage, and a decrease in phenolic acid contents were observed when spermidine degradation was inhibited. However, GABA application did attenuate an increase in electrolyte permeability and MDA content caused by UV-B induced oxidative damage and improved the respiration rate. Meanwhile, GABA application can elevate the accumulation of phenolic compounds by ca. 20%, by elevating the activities of some key enzymes. Furthermore, the application of GABA, together with the inhibitor of spermidine degradation, can alleviate its suppression of the synthesis of phenolic acids, and resistance to UV-B stress. In conclusion, spermidine alleviated oxidative damage and enhanced the accumulation of phenolic compounds using its degradation product.