KSHV vIL-6 promotes SIRT3-induced deacetylation of SERBP1 to inhibit ferroptosis and enhance cellular transformation by inducing lipoyltransferase 2 mRNA degradation.

Ferroptosis, a defensive strategy commonly employed by the host cells to restrict pathogenic infections, has been implicated in the development and therapeutic responses of various types of cancer. However, the role of ferroptosis in oncogenic Kaposi's sarcoma-associated herpesvirus (KSHV)-induced cancers remains elusive. While a growing number of non-histone proteins have been identified as acetylation targets, the functions of these modifications have yet to be revealed. Here, we show KSHV reprogramming of host acetylation proteomics following cellular transformation of rat primary mesenchymal precursor. Among them, SERPINE1 mRNA binding protein 1 (SERBP1) deacetylation is increased and required for KSHV-induced cellular transformation. Mechanistically, KSHV-encoded viral interleukin-6 (vIL-6) promotes SIRT3 deacetylation of SERBP1, preventing its binding to and protection of lipoyltransferase 2 (Lipt2) mRNA from mRNA degradation resulting in ferroptosis. Consequently, a SIRT3-specific inhibitor, 3-TYP, suppresses KSHV-induced cellular transformation by inducing ferroptosis. Our findings unveil novel roles of vIL-6 and SERBP1 deacetylation in regulating ferroptosis and KSHV-induced cellular transformation, and establish the vIL-6-SIRT3-SERBP1-ferroptosis pathways as a potential new therapeutic target for KSHV-associated cancers.

Evaluation of egg white hydrolysates on the hepatoprotective effect in vitro and in vivo.

The small molecule characteristics and nutritional value of egg white hydrolysates have been widely used. In the present study, in vitro and in vivo models were used to investigate the hepatoprotective effect of egg protein hydrolysate (EWH) by regulating the expression of antioxidant enzymes. The in vitro experiment results showed that 0.1, 0.5, and 1 mg/mL of EWH enhanced antioxidant activity in HepG2 cells by increased glutathione peroxidase (GPx) activity and reduced glutathione (GSH) levels. The in vivo experiment results showed that EWH (L) (38.5 mg/kg BW) and EWH (H) (385 mg/kg BW) alleviated carbon tetrachloride (CCl4)-induced hepatotoxicity in SD rats through reduced levels of serum aspartate aminotransferase (AST) alanine aminotransferase (ALT), and lipid peroxidation products malondialdehyde (MDA). In addition, EWH also ameliorates CCl4-induced hepatotoxicity in SD rats by increasing the antioxidant activity of GSH levels with a decrease in oxidized glutathione (GSSG) levels. Besides, EWH ameliorates liver tissue injuries by CCl4-induction. EWH has the highest glutamic acid in free amino acid composition, the second highest was aspartic acid, and the third was cystine, 204, 141, and 125 mg/100 g, respectively. These results suggest EWH has hepatoprotective potential through reduced lipid peroxidation products and enhanced antioxidant activity.

Effect of polyethylene microplastics on oxidative stress and histopathology damages in Litopenaeus vannamei.

There has been a significant increase in the microplastic (MP) polluting the ocean in recent time which is regarded as toxic for living organisms. In this study, Fluorescent red polyethylene microspheres (FRPE) were administered intramuscularly to Litopenaeus vannamei juveniles at the concentration of 0.1, 0.2, 0.5 and 1.0 µg (g shrimp)-1, and the survival rate was recorded. Analysis of the hepatopancreas for antioxidant enzyme activity and gene expression were done after seven days. Further tissue morphology and accumulation of FRPE was analysed. The results showed that FRPE at 0.5 and 1.0 µg (g shrimp)-1 reduce the survival rate of L. vannamei. FRPE at 0.5 and 1.0 µg (g shrimp)-1 reduced superoxide dismutase (SOD) activity; FRPE at different concentrations reduced catalase (CAT) activity; FRPE at 0.2, 0.5 and 1.0 µg (g shrimp)-1 increased the lipid peroxide thiobarbituric acid (TBARS) content. FRPE at 0.1, 0.2, and 0.5 µg (g shrimp)-1 significantly affect the performance of SOD and CAT genes; FRPE at 0.2 and 0.5 µg (g shrimp)-1 significantly improves GPx gene performance; FRPE at 1.0 µg (g shrimp)-1 significantly reduced the expression of GPx genes. Analysis of tissue morphology shows that FRPE cause muscle, midgut gland, and hepatopancreas, and gill damage at different concentrations. In the results of accumulation of microplastic, FRPE accumulated in gill tissue at 0.2 and 0.5 µg (g shrimp)-1; FRPE accumulated in gill, muscle and hepatopancreas tissue at 1.0 µg (g shrimp)-1. Based on the above results, FRPE at 0.5 and 1.0 µg (g shrimp)-1 can regulate the antioxidant enzymes of L. vannamei, increase lipid peroxide content, cause tissue damage by accumulating in the tissues. The rate of survival decreased in L. vannamei, and the impact of FRPE at 1.0 µg (g shrimp)-1 was significant.

UVA, UVB and UVC induce differential response signaling pathways converged on the eIF2α phosphorylation.

It is clear that solar UV irradiation is a crucial environmental factor resulting in skin diseases partially through activation of cell signaling toward altered gene expression and reprogrammed protein translation. Such a key translational control mechanism is executed by the eukaryotic initiation factor 2α subunit (eIF2α) and the downstream events provoked by phosphorylation of eIF2α at Ser(51) are clearly understood, but the upstream signaling mechanisms on the eIF2α-Ser(51) phosphorylation responses to different types of UV irradiations, namely UVA, UVB and UVC, are still not well elucidated. Herein, our evidence reveals that UVA, UVB and UVC all induce a dose- and time-dependent phosphorylation of eIF2α-Ser(51) through distinct signaling mechanisms. UVA-induced eIF2α phosphorylation occurs through MAPKs, including ERKs, JNKs and p38 kinase, and phosphatidylinositol (PI)-3 kinase. By contrast, UVB-induced eIF2α phosphorylation is through JNKs and p38 kinase, but not ERKs or PI-3 kinase, whereas UVC-stimulated response to eIF2α phosphorylation is via JNKs alone. Furthermore, we have revealed that ATM is involved in induction of the intracellular responses to UVA and UVB, rather than UVC. These findings demonstrate that wavelength-specific UV irradiations activate differential response signaling pathways converged on the eIF2α phosphorylation. Importantly, we also show evidence that a direct eIF2α kinase PKR is activated though phosphorylation by either RSK1 or MSK1, two downstream kinases of MAPKs/PI-3 kinase-mediated signaling pathways.