Voltage-dependent anion channel 2 (VDAC2) facilitates the accumulation of rice stripe virus in the vector Laodelphax striatellus.

Rice stripe virus (RSV) causes enormous losses in rice production and is transmitted by the small brown planthopper, Laodelphax striatellus, in a persistent-propagative manner. RSV accumulation within the gut lumen of the vector is indispensable for the successful transmission to rice and insects. In this study, we obtained a 1464 bp full-length cDNA of a voltage-dependent anion channel 2 from L. striatellus (LsVDAC2), which encodes a 283 amino acid protein. RSV infection increased the expression of LsVDAC2 in the midguts and ovaries of L. striatellus by 260% and 228%, respectively. Silencing of LsVDAC2 resulted in a 88% reduction of RSV loads at 24 h after RNAi, indicating that LsVDAC2 facilitates RSV accumulation in the vector. Yeast two-hybrid and GST pulldown assays demonstrated that LsVDAC2 interacted with RSV RNA-dependent RNA polymerase, RdRp. Furthermore, experiments in vivo and in vitro showed that LsVDAC2 induced the apoptotic response in RSV-infected insects and tissues. Silencing of LsVDAC2 via RNAi significantly reduced the expression of genes for apoptosis-related caspases 1a and 1c by 62% and 78%, respectively, in RSV-infected vectors. Whether LsVDAC2-induced RSV accumulation is related to RSV RdRp and LsVDAC2-induced cell apoptosis deserves further investigation.

Ascorbic acid and hydrocortisone synergistically inhibit septic organ injury via improving oxidative stress and inhibiting inflammation.

BACKGROUND: The current study aimed to investigate the effect of the combination of ascorbic acid (AscA) and hydrocortisone (Hyd) on septic organ injury and its potential mechanism. METHOD: Sepsis was induced in mice by a single intraperitoneal injection of lipopolysaccharides. RESULTS: AscA and Hyd combined showed more effective protection of the injured liver and kidney in septic mice by decreasing alanine aminotransferase, aspartate aminotransferase, serum urea nitrogen, and serum creatinine and ameliorating pathological manifestations than Hyd or AscA alone. AscA showed a mild inhibitory effect on the secretion of proinflammatory cytokines (tumor necrosis factor-alpha (TNF-α), interleukin-1ß (IL-1ß), and interleukin-6 (IL-6)). However, Hyd showed a weak regulatory effect on septic oxidative stress markers (malondialdehyde (MDA), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)). However, the combination of AscA and Hyd showed a more powerful inhibitory effect on the septic inflammatory response and oxidative stress than Hyd or AscA alone by decreasing TNF-α, IL-1ß, and IL-6 and regulating MDA, SOD, and GSH. In an in vitro study, cotreatment of RAW 264.7 macrophages with Hyd and AscA sharply reduced reactive oxygen species (ROS) generation and synergistically inhibited TNF-α, IL-1ß, and IL-6 secretion, which could be abolished by additional stimulation with the ROS donor 3-nitropropionic acid (3-NP). As expected, cotreatment of macrophages with Hyd and AscA synergistically inhibited the activation of p38 MAPK and p-p65, and the effect could be reversed by additional stimulation with 3-NP. CONCLUSIONS: AscA and Hyd synergistically protect the kidney and liver from injury by inhibiting the inflammatory response and oxidative stress. The powerful inhibitory effects of AscA on oxidative stress contribute to the synergistic anti-inflammatory action.