Thymopentin improves the survival of septic mice by promoting the production of 15-deoxy-prostaglandin J2 and activating the PPAR gamma signaling pathway
FASEB JOURNAL
Authors: Zhang, Ye; Yang, Xue; Yan, Wenchao; Li, Rui; Ye, Qian; You, Linjun; Xie, Wenhao; Mo, Kun; Fu, Ruifeng; Wang, Yanxiang; Chen, Yufei; Hou, Hui; Yang, Yong; Birnbaumer, Lutz; Di, Qin; Li, Xianjing
Abstract
Sepsis, a systemic inflammatory response syndrome (SIRS) caused by infection, is a major public health concern with limited therapeutic options. Infection disturbs the homeostasis of host, resulting in excessive inflammation and immune suppression. This has prompted the clinical use of immunomodulators to balance host response as an alternative therapeutic strategy. Here, we report that Thymopentin (TP5), a synthetic immunomodulator pentapeptide (Arg-Lys-Asp-Val-Tyr) with an excellent safety profile in the clinic, protects mice against cecal ligation and puncture (CLP)-induced sepsis, as shown by improved survival rate, decreased level of pro-inflammatory cytokines and reduced ratios of macrophages and neutrophils in spleen and peritoneum. Regarding mechanism, TP5 changed the characteristics of LPS-stimulated macrophages by increasing the production of 15-deoxy-Delta(12.14)-prostaelandin J2 (15-d-PGJ2). In addition, the improved effect of TP5 on survival rates was abolished by the peroxisome proliferator-activated receptor gamma (PPAR gamma) antagonist GW9662. Our results uncover the mechanism of the TP5 protective effects on CLP-induced sepsis and shed light on the development of TP5 as a therapeutic strategy for lethal systemic inflammatory disorders.
Characterization of methionine uptake and clearance in the hemolymph of Pacific white shrimp Litopenaeus vannamei
AQUACULTURE
Authors: Guo, Jingping; Duan, Mingming; Qiu, Xuan; Masagounder, Karthik; Davis, D. Allen
Abstract
A series of feeding trials were conducted to investigate the absorption rate of amino acids and compare the absorption of different methionine (Met) sources in the hemolymph of Pacific White shrimp, Litopenaeus vannamei. In trial 1, a basal diet was supplemented with three alpha amino acids including DL-Met, lysine and arginine and the beta amino acid taurine. Shrimp were fed with test diets for 30 mins and then the leftover feeds were withdrawn. The hemolymph samples were taken every 30 mins over 5 h after feeding to determine amino acid (AA) concentrations in the hemolymph. Results indicated that total AA, Met and Lys were near their peak after feeding 30 mins and the level declined within 60 mins to near fasting levels. No secondary peaks were observed for any AA. The diet supplemented with AA exhibited higher peaks than the basal diet. The second and third trials focused on the identification of different patterns that would indicate asynchronous absorption and comparison of the absorption of different Met sources. Four experimental diets were produced, including a basal diet (soy protein-based), a DL-Met-supplemented, a dipeptide Met (Met-Met)-supplemented, and a high fishmeal diet (high-Met intact protein) in trial 2. Fasted shrimp were offered diets for 15 mins and then the leftover feeds were removed. The hemolymph samples were taken every 15 mins over a 1 h period after feeding. The results generally confirmed the fast absorption and clearance of AA in shrimp and indicated that the diets containing different Met sources resulted in higher Met levels in the hemolymph as compared to the basal diet. To better define the absorption process and confirm if there may be a synchronous peak during absorption, the third trial simply looked at the uptake of AA over a 1 h period with basal diet and dipeptide Met diet. The shrimp were offered diets for a total of 60 mins during this timeframe intermittent samples were taken at 0, 5, 10, 15, 20, 30, and 60 mins. Results demonstrated the pattern for AA uptake is similar with a clear upswing in AA levels in 10-15 mins after the initiation of feeding. Based on both absorption and clearance patterns of the amino acids, we demonstrated that there were no indications of asynchronous absorption of supplemented amino acids; hence, supplemented amino acids are available for metabolism. In addition, the data also demonstrated higher peak of Met over time in the hemolymph of L. vannamei with the Met-Met supplemented diet versus the DL-Met supplemented diet.